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Yi M, Wang X, Li Y, Li X, Si J, Zhang Y, Xiao K, Sun L, Zhang H, Sun J, Liu Z, Lin J, Xie Y, Zhang B, Zhao J, Chu X, Li J. Association between Metabolic Syndrome Score and Subclinical Atherosclerosis. Rev Cardiovasc Med 2025; 26:26811. [PMID: 40160566 PMCID: PMC11951480 DOI: 10.31083/rcm26811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 12/12/2024] [Accepted: 01/13/2025] [Indexed: 04/02/2025] Open
Abstract
Background Previous studies have presented conflicting results on the correlation between metabolic syndrome (MetS) and subclinical atherosclerosis. However, the binary MetS definition cannot reflect the severity of metabolic disorders continuously and dynamically. The present study calculated the MetS score and explored the association between MetS score and subclinical atherosclerosis. Methods A total of 840 participants were included in this observational, cross-sectional study; 66.55% of participants were men, and the median age was 61.00 years (53.00, 67.00). Brachial-ankle pulse wave velocity (baPWV) and brachial flow-mediated dilation (bFMD) values were measured from October 2016 to January 2020. Spearman's correlation and multiple linear regression analyses were conducted to explore the correlation between the MetS score and baPWV and bFMD. Arterial stiffness was defined as baPWV ≥1400 cm/s, while endothelial dysfunction was described as bFMD >6%. Multiple logistic regression was performed to explore the effects of MetS and MetS score on arterial stiffness and endothelial dysfunction. Results The MetS score was significantly associated with baPWV (β = 73.59, 95% CI (42.70, 104.48); p < 0.001) and bFMD (β = -0.43, 95% CI (-0.75, -0.10); p = 0.010) after adjusting for covariates. Compared with the binary definition of MetS, the MetS score was a more significant predictor for arterial stiffness (odds ratio, OR = 2.63, 95% CI (1.85, 3.74); p < 0.001) and endothelial dysfunction (OR = 1.33, 95% CI (1.01, 1.76); p = 0.040). Leukocyte count (r = 0.32; p < 0.001) and high-sensitivity C-reactive protein (hs-CRP) (r = 0.17; p < 0.001) values were related to the MetS score. Conclusions The MetS score is a clinically accessible assessment of metabolic status that can identify individuals at higher risk of subclinical atherosclerosis.
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Affiliation(s)
- Ming Yi
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Xinyi Wang
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Yan Li
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Xuewen Li
- Department of the General Medicine, Characteristic Medical Center of Chinese People’s Armed Police Force, 300162 Tianjin, China
| | - Jin Si
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Yinghua Zhang
- Department of Cardiology, Chui Yang Liu Hospital Affiliated to Tsinghua University, 100021 Beijing, China
| | - Keling Xiao
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Lijie Sun
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Haoyu Zhang
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Jinghao Sun
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Zhaoli Liu
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Jiaying Lin
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Yuxin Xie
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Bingyan Zhang
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Jing Zhao
- Health Management Center, Xuanwu Hospital, Capital Medical University, 100053 Beijing, China
| | - Xi Chu
- Health Management Center, Xuanwu Hospital, Capital Medical University, 100053 Beijing, China
| | - Jing Li
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
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Martinotti S, Bonsignore G, Ranzato E. Propolis: A Natural Substance with Multifaceted Properties and Activities. Int J Mol Sci 2025; 26:1519. [PMID: 40003984 PMCID: PMC11855500 DOI: 10.3390/ijms26041519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 02/08/2025] [Accepted: 02/10/2025] [Indexed: 02/27/2025] Open
Abstract
Propolis (bee glue) is a complex mixture of resins, waxes, and gums, and it is a resinous exudate manufactured by honey bees to maintain the integrity of the hive and defend against external threats. This multifunctional material exhibits several striking properties. The anti-inflammatory properties of propolis have made it a subject of traditional medicine over time, from ancient Egyptian mummification to modern complementary medicine. Propolis with rich phytochemicals, such as polyphenols and flavonoids, exhibit anti-inflammatory, antioxidant, and anticancer effects. This review describes multiple properties and uses of propolis, highlighting the role of propolis as an exceptional natural resource with high therapeutic potential.
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Affiliation(s)
| | | | - Elia Ranzato
- Dipartimento di Scienze e Innovazione Tecnologica (DiSIT), University of Piemonte Orientale, 15121 Alessandria, Italy; (S.M.); (G.B.)
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Mukherjee S, Im SS. Decoding Health: Exploring Essential Biomarkers Linked to Metabolic Dysfunction-Associated Steatohepatitis and Type 2 Diabetes Mellitus. Biomedicines 2025; 13:359. [PMID: 40002771 PMCID: PMC11853123 DOI: 10.3390/biomedicines13020359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 01/24/2025] [Accepted: 02/03/2025] [Indexed: 02/27/2025] Open
Abstract
The investigation of biomarkers for metabolic diseases such as type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatohepatitis (MASH) reveals their potential for advancing disease treatment and addressing their notable overlap. The connection between MASH, obesity, and T2DM highlights the need for an integrative management approach addressing mechanisms like insulin resistance and chronic inflammation. Obesity contributes significantly to the development of MASH through lipid dysregulation, insulin resistance, and chronic inflammation. Selective biomarker targeting offers a valuable strategy for detecting these comorbidities. Biomarkers such as CRP, IL-6, and TNF-α serve as indicators of inflammation, while HOMA-IR, fasting insulin, and HbA1c are essential for evaluating insulin resistance. Additionally, triglycerides, LDL, and HDL are crucial for comprehending lipid dysregulation. Despite the growing importance of digital biomarkers, challenges in research methodologies and sample variability persist, necessitating further studies to validate diagnostic tools and improve health interventions. Future opportunities include developing non-invasive biomarker panels, using multiomics, and using machine learning to enhance prognoses for diagnostic accuracy and therapeutic outcomes.
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Affiliation(s)
| | - Seung-Soon Im
- Department of Physiology, Keimyung University School of Medicine, Daegu 42601, Republic of Korea
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Garg V, Ghay R, Goyal G, Saini RV. Exploring the Role of Acute Exercise-Induced Myokine Release in Glucose Metabolism and Insulin Sensitivity in Healthy and Diabetic Individuals. Cureus 2025; 17:e78991. [PMID: 40091956 PMCID: PMC11910891 DOI: 10.7759/cureus.78991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/14/2025] [Indexed: 03/19/2025] Open
Abstract
Background Exercise plays a significant role in influencing muscle metabolism and the secretion of myokines, which may have important therapeutic implications for managing type 2 diabetes mellitus (T2DM). This study explores the effects of a single session of moderate-intensity exercise on the levels of circulating myokines, specifically interleukin-6 (IL-6) and fractalkine, in individuals with T2DM compared to healthy controls. Methodology A total of 70 participants, including 35 individuals (50%) with T2DM and 35 healthy controls (50%) were enrolled in the study after taking their written informed consent. They took part in a 30-minute treadmill exercise session. Blood samples were collected before and after the exercise to measure fasting blood sugar (FBS), insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), IL-6, and fractalkine levels, allowing for an assessment of the exercise's effects on both groups. Results In the post-exercise period, both groups demonstrated significant improvements in FBS, insulin levels, and HOMA-IR. Notably, IL-6 levels increased, while fractalkine levels decreased, indicating exercise's beneficial metabolic and anti-inflammatory effects. However, it is important to note that no significant correlation was observed between myokine levels and the markers of glucose metabolism. Conclusions This study demonstrates that acute exercise positively impacts glucose regulation and myokine modulation in both T2DM and healthy individuals. The findings support the inclusion of exercise as an effective strategy for improving metabolic health in diabetes management, highlighting the role of muscle-derived myokines in regulating glucose metabolism. Further research is needed to explore the long-term effects and mechanistic pathways involved.
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Affiliation(s)
- Vaishali Garg
- Physiology, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, IND
| | - Richa Ghay
- Physiology and Medical Education, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, IND
| | - Gurdev Goyal
- Physiology, Maharishi Markandeshwar (Deemed to be University), Ambala, IND
| | - Reena V Saini
- Biosciences and Technology, Maharishi Markandeshwar (Deemed to be University), Ambala, IND
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Li Q, Zheng Y, Zhao J, Wei X, Shi Z, Fan H, Ge C, Xu M, Tan J. Radish red attenuates chronic kidney disease in obese mice through repressing oxidative stress and ferroptosis via Nrf2 signaling improvement. Int Immunopharmacol 2024; 143:113385. [PMID: 39549542 DOI: 10.1016/j.intimp.2024.113385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 10/03/2024] [Accepted: 10/08/2024] [Indexed: 11/18/2024]
Abstract
Chronic kidney disease (CKD) presents a significant public health concern, with obesity being a prominent contributing factor to kidney disorders by inducing oxidative stress, lipotoxicity, and tubular cell injury. Natural anthocyanins extracted from red radishes (Raphanus sativus L.) exert antioxidant and anti-apoptotic functions. This study aims to employ a novel natural pigment anthocyanin, referred to as radish red (RR) isolated from red radishes, to alleviate obesity-related metabolic disturbances and kidney impairment in a CKD mouse model induced by high-fat and high-fructose diets (HFFD). The in vitro study initially demonstrated that RR treatment significantly mitigated the palmitate acid (PA)-induced injury and cytotoxicity in human tubular epithelial HK2 cells. Subsequently, RR supplementation notably improved obesity and associated metabolic dysfunctions in mice caused by HFFD. Abnormal renal function indices including serum creatinine, blood urea nitrogen (BUN), uric acid (UA), urine protein, albuminuria and urine albumin-to-creatinine ratio (UACR) were detected in HFFD-fed mice, which were effectively alleviated by RR treatment. Histologically, renal tubular cell injury, lipid deposition, tubular dilatation, and renal fibrosis induced by HFFD were markedly improved after RR administration in mice. Furthermore, RR treatment significantly alleviated oxidative stress in HFFD-fed mice, as evidenced by the decreased renal reactive oxygen species (ROS) production, 4-HNE, and NOX4 expression levels. Anti-oxidants such as superoxide dismutase-1 (SOD1), NAD (P) H: quinone oxidoreductase (NQO1), heme oxygenase-1 (HO-1) and glutamate cysteine ligase (GCLC) were highly upregulated in kidney of HFFD-fed mice with RR consumption through improving NFE2-related factor 2 (Nrf2) signaling activation. Furthermore, ferroptosis was identified in the kidneys of HFFD-fed mice, evidenced by the elevated levels of malondialdehyde (MDA), iron content, and lipid peroxidation, along with the decreased expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). These occurrences were significantly mitigated following RR treatment. Mechanistically, we further discovered that the suppressive effects of RR in restricting oxidative stress, ferroptosis, lipid accumulation, and injury of tubular epithelial cells induced by PA were significantly counteracted by Nrf2 knockdown. Collectively, our results demonstrated that dietary supplementation with RR could potentially serve as an efficacious therapeutic modality for the management of obesity-related CKD progression by enhancing Nrf2 activation to impede oxidative stress and ferroptosis.
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Affiliation(s)
- Qiang Li
- Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, PR China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR China
| | - Yanbin Zheng
- Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, PR China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR China
| | - Jianyu Zhao
- Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, PR China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR China
| | - Xinyi Wei
- Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, PR China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR China
| | - Zongxin Shi
- Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, PR China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR China
| | - Haonan Fan
- Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, PR China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR China
| | - Chenxu Ge
- Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, PR China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR China; Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, PR China.
| | - Minxuan Xu
- Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, PR China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR China; Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, PR China.
| | - Jun Tan
- Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, PR China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR China; Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, PR China.
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Alcantara JMA, González-Acedo A, Amaro-Gahete FJ, Plaza-Florido A. Heart Rate and Its Variability Are Associated With Resting Metabolic Rate and Substrate Oxidation in Young Women but Not in Men. Am J Hum Biol 2024; 36:e24157. [PMID: 39300911 DOI: 10.1002/ajhb.24157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 08/20/2024] [Accepted: 09/02/2024] [Indexed: 09/22/2024] Open
Abstract
BACKGROUND This study aims to examine the relationship between resting vagal-related heart rate variability (HRV) parameters and heart rate (HR) with resting metabolic rate (RMR) and respiratory exchange ratio (RER) in young adults. METHODS A total of 74 young adults (22 ± 2 years old, 51 women) were included in this cross-sectional study. HRV was assessed using a HR monitor, whereas RMR and RER were determined by indirect calorimetry. RESULTS Linear regression analyses showed a positive association between HR and RER in women (standardized β = 0.384, p = 0.008), while negative associations were observed between vagal-related HRV parameters and RER in women (β ranged from -0.262 to -0.254, all p ≤ 0.042). No significant association was found between the abovementioned physiological parameters in men. CONCLUSION Here, we show that HR is positively associated with RER in young women but not in men, while vagal-related HRV parameters are inversely related to RMR, therefore suggesting a potential sexual dimorphism between cardiac rhythm and its relationship with markers of cardiometabolic health status. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT02365129.
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Affiliation(s)
- Juan M A Alcantara
- Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS), University of Granada, Granada, Spain
- Department of Health Sciences, Institute for Innovation & Sustainable Food Chain Development, Public University of Navarre, Pamplona, Spain
- Navarra Institute for Health Research, IdiSNA, Pamplona, Spain
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
| | - Anabel González-Acedo
- Department of Nursing, Faculty of Health Sciences, Biomedical Group (BIO277), University of Granada, Granada, Spain
| | - Francisco J Amaro-Gahete
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
- Instituto de Investigación Biosanitaria, Ibs.Granada, Granada, Spain
- Department of Physiology, Faculty of Medicine, University of Granada, Granada, Spain
| | - Abel Plaza-Florido
- Pediatric Exercise and Genomics Research Center, Department of Pediatrics, School of Medicine, University of California Irvine, Irvine, California, USA
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Giangregorio F, Mosconi E, Debellis MG, Provini S, Esposito C, Garolfi M, Oraka S, Kaloudi O, Mustafazade G, Marín-Baselga R, Tung-Chen Y. A Systematic Review of Metabolic Syndrome: Key Correlated Pathologies and Non-Invasive Diagnostic Approaches. J Clin Med 2024; 13:5880. [PMID: 39407941 PMCID: PMC11478146 DOI: 10.3390/jcm13195880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 09/26/2024] [Accepted: 09/27/2024] [Indexed: 10/20/2024] Open
Abstract
Background and Objectives: Metabolic syndrome (MetS) is a condition marked by a complex array of physiological, biochemical, and metabolic abnormalities, including central obesity, insulin resistance, high blood pressure, and dyslipidemia (characterized by elevated triglycerides and reduced levels of high-density lipoproteins). The pathogenesis develops from the accumulation of lipid droplets in the hepatocyte (steatosis). This accumulation, in genetically predisposed subjects and with other external stimuli (intestinal dysbiosis, high caloric diet, physical inactivity, stress), activates the production of pro-inflammatory molecules, alter autophagy, and turn on the activity of hepatic stellate cells (HSCs), provoking the low grade chronic inflammation and the fibrosis. This syndrome is associated with a significantly increased risk of developing type 2 diabetes mellitus (T2D), cardiovascular diseases (CVD), vascular, renal, pneumologic, rheumatological, sexual, cutaneous syndromes and overall mortality, with the risk rising five- to seven-fold for T2DM, three-fold for CVD, and one and a half-fold for all-cause mortality. The purpose of this narrative review is to examine metabolic syndrome as a "systemic disease" and its interaction with major internal medicine conditions such as CVD, diabetes, renal failure, and respiratory failure. It is essential for internal medicine practitioners to approach this widespread condition in a "holistic" rather than a fragmented manner, particularly in Western countries. Additionally, it is important to be aware of the non-invasive tools available for assessing this condition. Materials and Methods: We conducted an exhaustive search on PubMed up to July 2024, focusing on terms related to metabolic syndrome and other pathologies (heart, Lung (COPD, asthma, pulmonary hypertension, OSAS) and kidney failure, vascular, rheumatological (osteoarthritis, rheumatoid arthritis), endocrinological, sexual pathologies and neoplastic risks. The review was managed in accordance with the PRISMA statement. Finally, we selected 300 studies (233 papers for the first search strategy and 67 for the second one). Our review included studies that provided insights into metabolic syndrome and non-invasive techniques for evaluating liver fibrosis and steatosis. Studies that were not conducted on humans, were published in languages other than English, or did not assess changes related to heart failure were excluded. Results: The findings revealed a clear correlation between metabolic syndrome and all the pathologies above described, indicating that non-invasive assessments of hepatic fibrosis and steatosis could potentially serve as markers for the severity and progression of the diseases. Conclusions: Metabolic syndrome is a multisystem disorder that impacts organs beyond the liver and disrupts the functioning of various organs. Notably, it is linked to a higher incidence of cardiovascular diseases, independent of traditional cardiovascular risk factors. Non-invasive assessments of hepatic fibrosis and fibrosis allow clinicians to evaluate cardiovascular risk. Additionally, the ability to assess liver steatosis may open new diagnostic, therapeutic, and prognostic avenues for managing metabolic syndrome and its complications, particularly cardiovascular disease, which is the leading cause of death in these patients.
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Affiliation(s)
- Francesco Giangregorio
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Emilio Mosconi
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Maria Grazia Debellis
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Stella Provini
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Ciro Esposito
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Matteo Garolfi
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Simona Oraka
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Olga Kaloudi
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Gunel Mustafazade
- Department of Internal Medicine, Codogno Hospital, Via Marconi 1, 26900 Codogno, Italy; (F.G.); (E.M.); (M.G.D.); (S.P.); (C.E.); (M.G.); (S.O.); (G.M.)
| | - Raquel Marín-Baselga
- Department of Internal Medicine, Hospital Universitario La Paz, Paseo Castellana 241, 28046 Madrid, Spain;
| | - Yale Tung-Chen
- Department of Internal Medicine, Hospital Universitario La Paz, Paseo Castellana 241, 28046 Madrid, Spain;
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Huang W, Deng S, Liu S, Ma Q, Cao L, Liu L, Wan H, Shen J. Association of metabolic syndrome and sarcopenia with all-cause and cardiovascular mortality: a prospective cohort study based on the NHANES. Front Endocrinol (Lausanne) 2024; 15:1346669. [PMID: 38596221 PMCID: PMC11002088 DOI: 10.3389/fendo.2024.1346669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 03/12/2024] [Indexed: 04/11/2024] Open
Abstract
Background Metabolic syndrome (MetS) and sarcopenia (SP) have emerged as significant public health concerns in contemporary societies, characterized by shared pathophysiological mechanisms and interrelatedness, leading to profound health implications. In this prospective cohort study conducted within a US population, we aimed to examine the influence of MetS and SP on all-cause and cardiovascular mortality. Methods This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) III for the years 1999-2006 and 2011-2018, and death outcomes were ascertained by linkage to National Death Index (NDI) records through December 31, 2019. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause and cardiovascular mortality. In addition, subgroup and sensitivity analyses were conducted to test the robustness of the results. Results Over a median follow-up period of 13.3 years (95% CI: 12.8-13.8), 1714 deaths were observed. The groups characterized by MetS-/SP+, MetS+/SP-, and MetS+/SP+ exhibited higher all-cause mortality rates in comparison to the MetS-/SP- group, with the MetS+/SP+ group (HR 1.76, 95% CI: 1.37-2.25) displaying the highest all-cause mortality. Increased cardiovascular mortality was observed in the MetS+/SP- (HR 1.84, 95% CI: 1.24-2.72), and MetS+/SP+ groups (HR 2.39, 95% CI: 1.32-4.35) compared to the MetS-/SP- group, whereas it was not statistically significant in the MetS-/SP+ group. However, among males and individuals aged < 60, the presence of both MetS and SP (MetS+/SP+ group) was found to be significantly associated with a higher risk of all-cause and cardiovascular mortality. Conclusion The coexistence of MetS and SP increased the risk of all-cause and cardiovascular mortality, particularly in males and in nonelderly populations. Individuals with either MetS or SP may require more careful management to prevent the development of other diseases and thereby reduce mortality.
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Affiliation(s)
- Weihong Huang
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
| | - Siyi Deng
- Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Siyang Liu
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
| | - Qintao Ma
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
| | - Liting Cao
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
| | - Lan Liu
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
| | - Heng Wan
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
| | - Jie Shen
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, China
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Lai YJ, Yen YF, Chen LJ, Hsu LF, Ahmadi MN, Inan-Eroglu E, Biswas RK, Ku PW, Stamatakis E. Modification of incident cancer risk with changes in metabolic syndrome status: A prospective cohort study in Taiwan. Ann Epidemiol 2024; 91:65-73. [PMID: 38008235 DOI: 10.1016/j.annepidem.2023.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 10/27/2023] [Accepted: 11/20/2023] [Indexed: 11/28/2023]
Abstract
PURPOSE We aimed to investigate the effect of altered metabolic syndrome (MetS) status on cancer risk. METHODS From 2002 through 2008 of the Taiwan MJ cohort, there were 111,616 adults who had repeated MetS measurements performed 3.3 years apart and were followed up for cancer incidence over 11.8 years. Cancer was confirmed based on histopathological reports. RESULTS Participants were categorized as MetS-free (n = 80,409; no MetS at the first or last health screening), MetS-developed (n = 9833; MetS absence at the first screening and presence at the last screening), MetS-recovered (n = 8958; MetS presence at the first screening and absence at the last screening), and MetS-persisted (n = 12,416; MetS presence at the first and last screenings). We used the Fine-Gray sub-distribution method, with death as competing risk, to determine the association between MetS changes and incident cancer risk. During 1320,796 person-years of follow-up, 5862 individuals developed cancer. The incidence rate of cancer per 1000 person-years was 3.89 in the MetS-free, 5.26 in MetS-developed, 4.61 in MetS-recovered, and 7.33 in MetS-persisted groups (P < .001). Compared with the MetS-free group, MetS-persisted individuals had a higher risk of incident cancer. CONCLUSIONS Persistent MetS was found to be associated with a high risk of incident cancer.
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Affiliation(s)
- Yun-Ju Lai
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, Puli Branch of Taichung Veterans General Hospital, Nantou, Taiwan; Department of Exercise Health Science, National Taiwan University of Sport, Taichung, Taiwan; Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan
| | - Yung-Feng Yen
- Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan; Section of Infectious Diseases, Taipei City Hospital, Yangming Branch, Taipei, Taiwan; Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Education and Research, Taipei City Hospital, Taiwan.
| | - Li-Jung Chen
- Department of Exercise Health Science, National Taiwan University of Sport, Taichung, Taiwan
| | - Li-Fei Hsu
- College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Matthew N Ahmadi
- Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Australia
| | - Elif Inan-Eroglu
- Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Australia; Department of Molecular Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany
| | - Raaj Kishore Biswas
- Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Australia
| | - Po-Wen Ku
- Graduate Institute of Sports and Health Management, National Chung Hsing University, Taichung, Taiwan; Department of Kinesiology, National Tsing Hua University, Hsinchu, Taiwan
| | - Emmanuel Stamatakis
- Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Australia
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10
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Ju Z, Cui F, Mao Z, Li Z, Yi X, Zhou J, Cao J, Li X, Qian Z. miR-335-3p improves type II diabetes mellitus by IGF-1 regulating macrophage polarization. Open Med (Wars) 2024; 19:20240912. [PMID: 38463527 PMCID: PMC10921448 DOI: 10.1515/med-2024-0912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 12/21/2023] [Accepted: 01/22/2024] [Indexed: 03/12/2024] Open
Abstract
Previous studies have found that miR-335 is highly expressed in type II diabetes mellitus (T2DM) models and is related to insulin secretion, but there are few studies on the regulatory effects of miR-335-3p on insulin resistance and macrophage polarization in T2DM patients. This study aims to explore the effects of miR-335-3p on insulin resistance and macrophage polarization in T2DM patients. Blood glucose (insulin tolerance tests, glucose tolerance tests) and body weight of the T2DM model were measured; macrophages from adipose tissue were isolated and cultured, and the number of macrophages was detected by F4/80 immunofluorescence assay; the Real-time quantitative polymerase chain reaction (qPCR) assay and Western blot assay were used to detect the miR-335-3p expression levels, insulin-like growth factor 1 (IGF-1), M1-polarizing genes (inducible nitric oxide synthase [iNOS] and TNF-α) as well as M2-polarizing genes (IL-10 and ARG-1). The targeting link between miR-335-3p and IGF-1 was confirmed using bioinformatics and dual luciferase assay. The results showed that miR-335-3p expression level in adipose tissue of the T2DM model was significantly decreased, and the mice's body weight and blood glucose levels dropped considerably, miR-335-3p inhibited the number of macrophages, inhibiting the iNOS and TNF-α relative mRNA expression levels, and up-regulated the IL-10 and ARG-1 relative mRNA expression levels, miR-335-3p negatively regulated target gene IGF-1, IGF-1 significantly increased the iNOS and TNF-α mRNA and protein expression levels, decreasing the IL-10 and ARG-1 mRNA and protein expression levels, indicating that miR-335-3p could affect the T2DM process by regulating macrophage polarization via IGF-1.
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Affiliation(s)
- Zhengzheng Ju
- Department of Clinical Laboratory, Wuhu Hospital Affiliated to Anhui University of Science and Technology (The First People’s Hospital of Wuhu), Wuhu, Anhui, China
| | - Fan Cui
- Department of Clinical Laboratory, Wuhu Hospital Affiliated to Anhui University of Science and Technology (The First People’s Hospital of Wuhu), Wuhu, Anhui, China
| | - Zheng Mao
- Department of Clinical Laboratory, Wuhu Hospital Affiliated to Anhui University of Science and Technology (The First People’s Hospital of Wuhu), Wuhu, Anhui, China
| | - Zhen Li
- Department of Clinical Laboratory, Wuhu Hospital Affiliated to Anhui University of Science and Technology (The First People’s Hospital of Wuhu), Wuhu, Anhui, China
| | - Xiayu Yi
- Department of Clinical Laboratory, Wuhu Hospital Affiliated to Anhui University of Science and Technology (The First People’s Hospital of Wuhu), Wuhu, Anhui, China
| | - Jingjing Zhou
- Department of Clinical Laboratory, Wuhu Hospital Affiliated to Anhui University of Science and Technology (The First People’s Hospital of Wuhu), Wuhu, Anhui, China
| | - Jinjin Cao
- Department of Clinical Laboratory, Wuhu Hospital Affiliated to Anhui University of Science and Technology (The First People’s Hospital of Wuhu), Wuhu, Anhui, China
| | - Xiaoqin Li
- Department of Clinical Laboratory, Wuhu Hospital Affiliated to Anhui University of Science and Technology (The First People’s Hospital of Wuhu), Wuhu, Anhui, China
| | - Zengkun Qian
- Department of Clinical Laboratory, Wuhu Hospital Affiliated to Anhui University of Science and Technology (The First People’s Hospital of Wuhu), Wuhu, Anhui, China
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11
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Alemany M. The Metabolic Syndrome, a Human Disease. Int J Mol Sci 2024; 25:2251. [PMID: 38396928 PMCID: PMC10888680 DOI: 10.3390/ijms25042251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 01/29/2024] [Accepted: 01/31/2024] [Indexed: 02/25/2024] Open
Abstract
This review focuses on the question of metabolic syndrome (MS) being a complex, but essentially monophyletic, galaxy of associated diseases/disorders, or just a syndrome of related but rather independent pathologies. The human nature of MS (its exceptionality in Nature and its close interdependence with human action and evolution) is presented and discussed. The text also describes the close interdependence of its components, with special emphasis on the description of their interrelations (including their syndromic development and recruitment), as well as their consequences upon energy handling and partition. The main theories on MS's origin and development are presented in relation to hepatic steatosis, type 2 diabetes, and obesity, but encompass most of the MS components described so far. The differential effects of sex and its biological consequences are considered under the light of human social needs and evolution, which are also directly related to MS epidemiology, severity, and relations with senescence. The triggering and maintenance factors of MS are discussed, with especial emphasis on inflammation, a complex process affecting different levels of organization and which is a critical element for MS development. Inflammation is also related to the operation of connective tissue (including the adipose organ) and the widely studied and acknowledged influence of diet. The role of diet composition, including the transcendence of the anaplerotic maintenance of the Krebs cycle from dietary amino acid supply (and its timing), is developed in the context of testosterone and β-estradiol control of the insulin-glycaemia hepatic core system of carbohydrate-triacylglycerol energy handling. The high probability of MS acting as a unique complex biological control system (essentially monophyletic) is presented, together with additional perspectives/considerations on the treatment of this 'very' human disease.
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Affiliation(s)
- Marià Alemany
- Faculty of Biology, Universitat de Barcelona, 08028 Barcelona, Catalonia, Spain
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12
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Li LY, Liu SF, Zhuang JL, Li MM, Huang ZP, Chen YH, Chen XR, Chen CN, Lin S, Ye LC. Recent research progress on metabolic syndrome and risk of Parkinson's disease. Rev Neurosci 2023; 34:719-735. [PMID: 36450297 DOI: 10.1515/revneuro-2022-0093] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 11/06/2022] [Indexed: 10/05/2023]
Abstract
Parkinson's disease (PD) is one of the most widespread neurodegenerative diseases. PD is associated with progressive loss of substantia nigra dopaminergic neurons, including various motor symptoms (e.g., bradykinesia, rigidity, and resting tremor), as well as non-motor symptoms (e.g., cognitive impairment, constipation, fatigue, sleep disturbance, and depression). PD involves multiple biological processes, including mitochondrial or lysosomal dysfunction, oxidative stress, insulin resistance, and neuroinflammation. Metabolic syndrome (MetS), a collection of numerous connected cerebral cardiovascular conditions, is a common and growing public health problem associated with many chronic diseases worldwide. MetS components include central/abdominal obesity, systemic hypertension, diabetes, and atherogenic dyslipidemia. MetS and PD share multiple pathophysiological processes, including insulin resistance, oxidative stress, and chronic inflammation. In recent years, MetS has been linked to an increased risk of PD, according to studies; however, the specific mechanism remains unclear. Researchers also found that some related metabolic therapies are potential therapeutic strategies to prevent and improve PD. This article reviews the epidemiological relationship between components of MetS and the risk of PD and discusses the potentially relevant mechanisms and recent progress of MetS as a risk factor for PD. Furthermore, we conclude that MetS-related therapies are beneficial for the prevention and treatment of PD.
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Affiliation(s)
- Lin-Yi Li
- Department of Neurology, The Second Affiliated Hospital, Fujian Medical University, No. 34 North Zhongshan Road, Quanzhou 362000, Fujian Province, China
| | - Shu-Fen Liu
- Department of Neurology, The Second Affiliated Hospital, Fujian Medical University, No. 34 North Zhongshan Road, Quanzhou 362000, Fujian Province, China
| | - Jian-Long Zhuang
- Prenatal Diagnosis Center, Quanzhou Women's and Children's Hospital, Quanzhou 362000, China
| | - Mi-Mi Li
- Department of Neurology, The Second Affiliated Hospital, Fujian Medical University, No. 34 North Zhongshan Road, Quanzhou 362000, Fujian Province, China
| | - Zheng-Ping Huang
- Department of Neurology, The Second Affiliated Hospital, Fujian Medical University, No. 34 North Zhongshan Road, Quanzhou 362000, Fujian Province, China
| | - Yan-Hong Chen
- Department of Neurology, Shishi General Hospital, Quanzhou 362000, Fujian Province, China
| | - Xiang-Rong Chen
- Department of Neurosurgery, The Second Affiliated Hospital, Fujian Medical University, Quanzhou 362000, Fujian Province, China
| | - Chun-Nuan Chen
- Department of Neurology, The Second Affiliated Hospital, Fujian Medical University, No. 34 North Zhongshan Road, Quanzhou 362000, Fujian Province, China
| | - Shu Lin
- Centre of Neurological and Metabolic Research, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian Province, China
- Group of Neuroendocrinology, Garvan Institute of Medical Research, 384 Victoria St, Sydney, NSW, Australia
| | - Li-Chao Ye
- Department of Neurology, The Second Affiliated Hospital, Fujian Medical University, No. 34 North Zhongshan Road, Quanzhou 362000, Fujian Province, China
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13
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Ren J, Wang XQ, Nakao T, Libby P, Shi GP. Differential Roles of Interleukin-6 in Severe Acute Respiratory Syndrome-Coronavirus-2 Infection and Cardiometabolic Diseases. CARDIOLOGY DISCOVERY 2023; 3:166-182. [PMID: 38152628 PMCID: PMC10750760 DOI: 10.1097/cd9.0000000000000096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2023]
Abstract
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection can lead to a cytokine storm, unleashed in part by pyroptosis of virus-infected macrophages and monocytes. Interleukin-6 (IL-6) has emerged as a key participant in this ominous complication of COVID-19. IL-6 antagonists have improved outcomes in patients with COVID-19 in some, but not all, studies. IL-6 signaling involves at least 3 distinct pathways, including classic-signaling, trans-signaling, and trans-presentation depending on the localization of IL-6 receptor and its binding partner glycoprotein gp130. IL-6 has become a therapeutic target in COVID-19, cardiovascular diseases, and other inflammatory conditions. However, the efficacy of inhibition of IL-6 signaling in metabolic diseases, such as obesity and diabetes, may depend in part on cell type-dependent actions of IL-6 in controlling lipid metabolism, glucose uptake, and insulin sensitivity owing to complexities that remain to be elucidated. The present review sought to summarize and discuss the current understanding of how and whether targeting IL-6 signaling ameliorates outcomes following SARS-CoV-2 infection and associated clinical complications, focusing predominantly on metabolic and cardiovascular diseases.
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Affiliation(s)
- Jingjing Ren
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115
| | - Xiao-Qi Wang
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115
| | - Tetsushi Nakao
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115
| | - Peter Libby
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115
| | - Guo-Ping Shi
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115
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14
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Okutsu S, Kato Y, Takeoka H, Funakoshi S, Maeda T, Yoshimura C, Kawazoe M, Satoh A, Tada K, Takahashi K, Ito K, Yasuno T, Fujii H, Mukoubara S, Saku K, Kodama S, Kawanami D, Masutani K, Arima H, Nabeshima S. Elevation in white blood cell count and development of hyper LDL cholesterolemia. Sci Rep 2023; 13:8292. [PMID: 37217577 DOI: 10.1038/s41598-023-35436-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 05/18/2023] [Indexed: 05/24/2023] Open
Abstract
To investigate the relationship between white blood cell (WBC) count and incidence of hyper-low-density lipoprotein (LDL) cholesterolemia in a population-based longitudinal study. This is a retrospective study using data of annual health check-ups for residents of Iki City, Japan. A total of 3312 residents (≥ 30 years) without hyper-LDL cholesterolemia at baseline were included in this analysis. Primary outcome was incidence of hyper-LDL cholesterolemia (LDL cholesterol levels ≥ 3.62 mmol/L and/or use of lipid lowering drugs). During follow-up (average 4.6 years), 698 participants development of hyper-LDL cholesterolemia (incidence 46.8 per 1000 person-years). Higher incidence of hyper-LDL cholesterolemia was observed among participants with higher leukocyte count (1st quartile group: 38.5, 2nd quartile group: 47.7, 3rd quartile group: 47.3, and 4th quartile group: 52.4 per 1,000 person-years, P = 0.012 for trend). Statistically significant relation was observed even after adjustment for age, gender, smoking, alcohol intake, leisure-time exercise, obesity, hypertension and diabetes: hazard ratio 1.24 (95% confidence interval 0.99 to 1.54) for 2nd quartile group, 1.29 (1.03-1.62) for 3rd quartile group and 1.39 (1.10-1.75) for 4th quartile group, compared with 1st quartile group (P for trend = 0.006). Increased WBC count was related to incidence of hyper-LDL cholesterolemia in general Japanese population.
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Affiliation(s)
- Shota Okutsu
- Department of General Medicine, Faculty of Medicine, Fukuoka University School of Medicine, Fukuoka, Japan
- Department of Preventive Medicine and Public Health, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Yoshifumi Kato
- Department of General Medicine, Faculty of Medicine, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Hiroaki Takeoka
- Department of General Medicine, Faculty of Medicine, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Shunsuke Funakoshi
- Department of Preventive Medicine and Public Health, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Toshiki Maeda
- Department of Preventive Medicine and Public Health, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Chikara Yoshimura
- Department of Preventive Medicine and Public Health, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Miki Kawazoe
- Department of Preventive Medicine and Public Health, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Atsushi Satoh
- Department of Preventive Medicine and Public Health, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Kazuhiro Tada
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Koji Takahashi
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Kenji Ito
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Tetsuhiko Yasuno
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Hideyuki Fujii
- Department of Endocrinology and Diabetes Mellitus, Fukuoka University School of Medicine, Fukuoka, Japan
| | | | - Keijiro Saku
- Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Shohta Kodama
- Department of Regenerative Medicine and Transplantation, Faculty of Medicine, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Daiji Kawanami
- Department of Endocrinology and Diabetes Mellitus, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Kosuke Masutani
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Hisatomi Arima
- Department of Preventive Medicine and Public Health, Fukuoka University School of Medicine, Fukuoka, Japan.
| | - Shigeki Nabeshima
- Department of General Medicine, Faculty of Medicine, Fukuoka University School of Medicine, Fukuoka, Japan
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15
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Zhang X, Ohayon-Steckel L, Coppin E, Johny E, Dasari A, Florentin J, Vasamsetti S, Dutta P. Epidermal Growth Factor Receptor in Hepatic Endothelial Cells Suppresses MCP-1-Dependent Monocyte Recruitment in Diabetes. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2023; 210:1363-1371. [PMID: 36946774 PMCID: PMC10121888 DOI: 10.4049/jimmunol.2200557] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 02/27/2023] [Indexed: 03/23/2023]
Abstract
Insulin resistance is a compromised response to insulin in target tissues such as liver. Emerging evidence shows that vascular endothelial cells (ECs) are critical in mediating glucose metabolism. However, how liver ECs can regulate inflammation in the setting of insulin resistance is still unknown. Using genome-wide transcriptome analysis of ECs isolated from diabetic mice, we found enrichment of the genes involved in epidermal growth factor receptor (Egfr) signaling. In line with this, hepatic sinusoidal ECs in diabetic mice had elevated levels of Egfr expression. Interestingly, we found an increased number of hepatic myeloid cells, especially macrophages, and systemic glucose intolerance in Cdh5Cre/+Egfrfl/fl mice lacking Egfr in ECs compared with littermate control mice with type II diabetes. Egfr deficiency upregulated the expression of MCP-1 in hepatic sinusoidal ECs. This resulted in augmented monocyte recruitment and macrophage differentiation in Cdh5Cre/+Egfrfl/fl mice compared with littermate control mice as determined by a mouse model of parabiosis. Finally, MCP-1 neutralization and hepatic macrophage depletion in Cdh5Cre/+Egfrfl/fl mice resulted in a reduced number of hepatic macrophages and ameliorated glucose intolerance compared with the control groups. Collectively, these results demonstrate a protective endothelial Egfr signaling in reducing monocyte-mediated hepatic inflammation and glucose intolerance in type II diabetic mice.
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Affiliation(s)
- Xinyi Zhang
- Department of Cardiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Lee Ohayon-Steckel
- Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Emilie Coppin
- Regeneration in Hematopoiesis, Institute for Immunology, TU Dresden, Dresden, Germany
- Immunology of Aging, Leibniz Institute on Aging – Fritz Lipmann Institute, Jena, Germany
| | - Ebin Johny
- Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Ankush Dasari
- Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Jonathan Florentin
- Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Sathish Vasamsetti
- Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Partha Dutta
- Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
- Pittsburgh VA Medical Center-University Drive, University Drive C, Pittsburgh, PA, 15213
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16
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Sajjadi SS, Bagherniya M, Soleimani D, Siavash M, Askari G. Effect of propolis on mood, quality of life, and metabolic profiles in subjects with metabolic syndrome: a randomized clinical trial. Sci Rep 2023; 13:4452. [PMID: 36932147 PMCID: PMC10022550 DOI: 10.1038/s41598-023-31254-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 03/08/2023] [Indexed: 03/19/2023] Open
Abstract
Metabolic syndrome (MeS) is a common multifaceted disorder. Plants contain antioxidant bioactive compounds, which are beneficial to improve the health condition of patients with MeS. Propolis is a hive natural product that is composed of various constituent. We aimed to assess the effects of Iranian propolis as a natural and safe agent on indicators of MeS, quality of life and mood status in individuals with MeS. In total, 66 interested eligible patients recruited to the present study. Participants were randomly assigned to consume a tablet at dose of 250 mg of propolis extract, twice daily for 12 weeks or placebo. Propolis supplementation could lead to a significant reduction in waist circumference (WC), increase in physical functioning, general health and the overall score of SF-36 compared with placebo group (P-value < 0.05). However, no significant differences were observed regarding other anthropometric indices and biochemical parameters between two groups (P-value > 0.05). The current study indicated that propolis can be effective in decreasing WC and improving physical health and quality of life, while had no significant effects on other components of MeS among subjects with this syndrome. Clinical trials registration Iran Registry of Clinical Trials.ir IRCT20121216011763N49, registration date 23/12/2020.
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Affiliation(s)
- Sana Sadat Sajjadi
- Nutrition and Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Bagherniya
- Nutrition and Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
- Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Davood Soleimani
- Research Center of Oils and Fats, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Nutritional Sciences Department, School of Nutrition Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mansour Siavash
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Gholamreza Askari
- Nutrition and Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.
- Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
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17
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The Synergistic Action of Metformin and Glycyrrhiza uralensis Fischer Extract Alleviates Metabolic Disorders in Mice with Diet-Induced Obesity. Int J Mol Sci 2023; 24:ijms24020936. [PMID: 36674447 PMCID: PMC9862386 DOI: 10.3390/ijms24020936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 12/31/2022] [Accepted: 01/02/2023] [Indexed: 01/06/2023] Open
Abstract
Metformin, an antidiabetic drug, and Glycyrrhiza uralensis Fischer (GU), an oriental medicinal herb, have been reported to exert anti-obesity effects. This study investigated the synergistic action of metformin and GU in improving diet-induced obesity. Mice were fed a normal diet, a high-fat diet (HFD), or HFD + 0.015% GU water extract for 8 weeks. The HFD and GU groups were then randomly divided into two groups and fed the following diets for the next 8 weeks: HFD with 50 mg/kg metformin (HFDM) and GU with 50 mg/kg metformin (GUM). GUM prevented hepatic steatosis and adiposity by suppressing expression of mRNAs and enzyme activities related to lipogenesis in the liver and upregulating the expression of adipocyte mRNAs associated with fatty acid oxidation and lipolysis, and as a result, improved dyslipidemia. Moreover, GUM improved glucose homeostasis by inducing glucose uptake in tissues and upregulating mRNA expressions associated with glycolysis in the liver and muscle through AMP-activated protein kinase activation. GUM also improved inflammation by increasing antioxidant activity in the liver and erythrocytes and decreasing inflammatory cytokine productions. Here, we demonstrate that GU and metformin exert synergistic action in the prevention of obesity and its complications.
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18
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Wang H, Wang Y, Li X, Deng X, Kong Y, Wang W, Zhou Y. Machine learning of plasma metabolome identifies biomarker panels for metabolic syndrome: findings from the China Suboptimal Health Cohort. Cardiovasc Diabetol 2022; 21:288. [PMID: 36564831 PMCID: PMC9789589 DOI: 10.1186/s12933-022-01716-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 12/02/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Metabolic syndrome (MetS) has been proposed as a clinically identifiable high-risk state for the prediction and prevention of cardiovascular diseases and type 2 diabetes mellitus. As a promising "omics" technology, metabolomics provides an innovative strategy to gain a deeper understanding of the pathophysiology of MetS. The study aimed to systematically investigate the metabolic alterations in MetS and identify biomarker panels for the identification of MetS using machine learning methods. METHODS Nuclear magnetic resonance-based untargeted metabolomics analysis was performed on 1011 plasma samples (205 MetS patients and 806 healthy controls). Univariate and multivariate analyses were applied to identify metabolic biomarkers for MetS. Metabolic pathway enrichment analysis was performed to reveal the disturbed metabolic pathways related to MetS. Four machine learning algorithms, including support vector machine (SVM), random forest (RF), k-nearest neighbor (KNN), and logistic regression were used to build diagnostic models for MetS. RESULTS Thirteen significantly differential metabolites were identified and pathway enrichment revealed that arginine, proline, and glutathione metabolism are disturbed metabolic pathways related to MetS. The protein-metabolite-disease interaction network identified 38 proteins and 23 diseases are associated with 10 MetS-related metabolites. The areas under the receiver operating characteristic curve of the SVM, RF, KNN, and logistic regression models based on metabolic biomarkers were 0.887, 0.993, 0.914, and 0.755, respectively. CONCLUSIONS The plasma metabolome provides a promising resource of biomarkers for the predictive diagnosis and targeted prevention of MetS. Alterations in amino acid metabolism play significant roles in the pathophysiology of MetS. The biomarker panels and metabolic pathways could be used as preventive targets in dealing with cardiometabolic diseases related to MetS.
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Affiliation(s)
- Hao Wang
- Department of Clinical Epidemiology and Evidence-Based Medicine, Beijing Clinical Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Youxin Wang
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, 100069, China
| | - Xingang Li
- Center for Precision Medicine, School of Medical and Health Sciences, Edith Cowan University, Perth, WA6027, Australia
| | - Xuan Deng
- Clinical Research Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Hongkou District, Shanghai, 200080, China
| | - Yuanyuan Kong
- Department of Clinical Epidemiology and Evidence-Based Medicine, Beijing Clinical Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Wei Wang
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, 100069, China
- Center for Precision Medicine, School of Medical and Health Sciences, Edith Cowan University, Perth, WA6027, Australia
| | - Yong Zhou
- Clinical Research Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Hongkou District, Shanghai, 200080, China.
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19
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Mosquera-Sulbarán J, Ryder E, Pedreáñez A, Vargas R. Angiotensin II and human obesity. A narrative review of the pathogenesis. INVESTIGACIÓN CLÍNICA 2022. [DOI: 10.54817/ic.v63n4a09] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Angiotensin II (Ang II) is a hormone and the main effector of the renin-angiotensin system (RAS). This peptide has crucial pathophysiologi-cal effects on hypertension, cardiac hypertrophy, endothelial proliferation, in-flammation and tissue remodelling through G protein-coupled receptors. The pro-inflammatory role of Ang II has been reported in various inflammatory pro-cesses. Obesity is linked to a chronic inflammatory process which in turn is the cause of some of its morbidities. Ang II is related to the comorbidities related to the comorbidities of obesity, which include alterations in the heart, kid-ney, hypertension and coagulation. In this regard, activation of AT1 receptors by Ang II can induce an inflammatory process mediated by the transcription factor NF-kB, triggering inflammation in various systems that are related to the comorbidities observed in obesity. The aim of this review was to highlight the pro-inflammatory effects of Ang II and the alterations induced by this hor-mone in various organs and systems in obesity. The search was done since 1990 through Medline, EMBASE and PubMed, using the keywords: angiotensin II; an-giotensin II, obesity; angiotensin II, kidney, obesity; angiotensin II, coagulation, obesity; angiotensin II, inflammation, obesity; angiotensin II, adipose tissue, obesity; angiotensin II, hypertension, obesity; angiotensin II, insulin resistance, obesity; angiotensin II, adiponectin, leptin, obesity; angiotensin II, COVID-19, obesity. Angiotensin II through its interaction with its AT1 receptor, can induce alterations in diverse systems that are related to the comorbidities observed in obesity. Therapeutic strategies to decrease the production and action of Ang II could improve the clinical conditions in individuals with obesity.
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Affiliation(s)
- Jesús Mosquera-Sulbarán
- Instituto de Investigaciones Clínicas “Dr. Américo Negrette”, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela
| | - Elena Ryder
- Instituto de Investigaciones Clínicas “Dr. Américo Negrette”, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela
| | - Adriana Pedreáñez
- Cátedra de Inmunología, Escuela de Bioanálisis, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela
| | - Renata Vargas
- Instituto de Investigaciones Clínicas “Dr. Américo Negrette”, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela
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20
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González-Acedo A, Plaza-Florido A, Amaro-Gahete FJ, Sacha J, Alcantara JMA. Associations between heart rate variability and maximal fat oxidation in two different cohorts of healthy sedentary adults. Nutr Metab Cardiovasc Dis 2022; 32:2338-2347. [PMID: 35977864 DOI: 10.1016/j.numecd.2022.06.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 05/12/2022] [Accepted: 06/15/2022] [Indexed: 10/17/2022]
Abstract
BACKGROUND AND AIMS Resting heart rate variability (HRV) and maximal fat oxidation (MFO) during exercise are both considered as a noninvasive biomarkers for early detection of cardiovascular risk factors. Thus, this study aimed to analyze the relationship between resting HRV parameters and MFO during exercise, and the intensity of exercise that elicit MFO (Fatmax) in healthy sedentary adults. METHODS AND RESULTS A total of 103 healthy young adults (22.2 ± 2.3 years old, 67% female; from the ACTIBATE cohort) and 67 healthy middle-aged adults (53.1 ± 5.0 years old, 52% female; from the FIT-AGEING cohort) were included in this cross-sectional study. HRV was assessed using a Polar RS800CX heart rate monitor, while MFO and Fatmax were determined during a graded exercise treadmill test using indirect calorimetry. No significant associations were observed for healthy young adults (standardized β coefficients ranged from -0.063 to 0.094, and all P ≥ 0.347) and for middle-aged adults (standardized β coefficients ranged from -0.234 to 0.090, and all P ≥ 0.056). Nevertheless, only a weak association was observed between one HRV parameter in time-domain (the percentage of R-R intervals that shows a difference higher than 50 ms [pNN50]) and MFO in the cohort of middle-aged adults (β coefficient = -0.279, and P = 0.033). CONCLUSION The results of this study suggest that resting HRV parameters are not associated with MFO and Fatmax during exercise in two independent cohorts of healthy sedentary young and middle-aged adults, respectively.
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Affiliation(s)
- Anabel González-Acedo
- Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences, University of Granada (Spain), Avda. Ilustración, 60, 18016, Spain.
| | - Abel Plaza-Florido
- PROFITH "PROmoting FITness and Health Through Physical Activity" Research Group, Sport and Health University Research Institute (iMUDS), Department of Physical and Sports Education, Faculty of Sport Sciences, University of Granada, Spain.
| | - Francisco José Amaro-Gahete
- PROFITH "PROmoting FITness and Health Through Physical Activity" Research Group, Sport and Health University Research Institute (iMUDS), Department of Physical and Sports Education, Faculty of Sport Sciences, University of Granada, Spain; EFFECTS-262 Research Group, Department of Physiology, School of Medicine, University of Granada, Spain.
| | - Jerzy Sacha
- Faculty of Physical Education and Physiotherapy, Opole University of Technology, Opole, Poland; Department of Cardiology, University Hospital in Opole, University of Opole, Opole, Poland.
| | - Juan M A Alcantara
- PROFITH "PROmoting FITness and Health Through Physical Activity" Research Group, Sport and Health University Research Institute (iMUDS), Department of Physical and Sports Education, Faculty of Sport Sciences, University of Granada, Spain.
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21
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Lucotti S, Kenific CM, Zhang H, Lyden D. Extracellular vesicles and particles impact the systemic landscape of cancer. EMBO J 2022; 41:e109288. [PMID: 36052513 PMCID: PMC9475536 DOI: 10.15252/embj.2021109288] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 02/16/2022] [Accepted: 03/23/2022] [Indexed: 11/09/2022] Open
Abstract
Intercellular cross talk between cancer cells and stromal and immune cells is essential for tumor progression and metastasis. Extracellular vesicles and particles (EVPs) are a heterogeneous class of secreted messengers that carry bioactive molecules and that have been shown to be crucial for this cell-cell communication. Here, we highlight the multifaceted roles of EVPs in cancer. Functionally, transfer of EVP cargo between cells influences tumor cell growth and invasion, alters immune cell composition and function, and contributes to stromal cell activation. These EVP-mediated changes impact local tumor progression, foster cultivation of pre-metastatic niches at distant organ-specific sites, and mediate systemic effects of cancer. Furthermore, we discuss how exploiting the highly selective enrichment of molecules within EVPs has profound implications for advancing diagnostic and prognostic biomarker development and for improving therapy delivery in cancer patients. Altogether, these investigations into the role of EVPs in cancer have led to discoveries that hold great promise for improving cancer patient care and outcome.
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Affiliation(s)
- Serena Lucotti
- Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer CenterWeill Cornell MedicineNew YorkNYUSA
| | - Candia M Kenific
- Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer CenterWeill Cornell MedicineNew YorkNYUSA
| | - Haiying Zhang
- Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer CenterWeill Cornell MedicineNew YorkNYUSA
| | - David Lyden
- Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer CenterWeill Cornell MedicineNew YorkNYUSA
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22
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Nirwan N, Vohora D. Linagliptin in Combination With Metformin Ameliorates Diabetic Osteoporosis Through Modulating BMP-2 and Sclerostin in the High-Fat Diet Fed C57BL/6 Mice. Front Endocrinol (Lausanne) 2022; 13:944323. [PMID: 35928902 PMCID: PMC9343600 DOI: 10.3389/fendo.2022.944323] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Accepted: 06/22/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Diabetic osteoporosis is a poorly managed serious skeletal complication, characterized by high fracture risk, increased bone resorption, reduced bone formation, and disrupted bone architecture. There is a need to investigate drugs that can improve bone health along with managing glycemic control. DPP-4 inhibitors and metformin have proven benefits in improving bone health. Here, we investigated the effects of linagliptin, a DPP inhibitor, and metformin alone and in combination to treat diabetic osteoporosis in high-fat-fed mice. METHODS C57BL/6 mice were kept on the high-fat diet (HFD) for 22 weeks to induce diabetic osteoporosis. Linagliptin (10mg/Kg), metformin (150mg/Kg), and their combination were orally administered to the diabetic mice from the 18th-22nd week. Femur and tibial bone microarchitecture together with bone mineral density (BMD) were evaluated using µCT and histopathological changes were assessed. Further, bone turnover biomarkers namely bone morphogenetic protein-2 (BMP-2), sclerostin, tartrate-resistant acid phosphatase (TRAP), osteocalcin, alkaline phosphatase (ALP), calcium, and pro-inflammatory cytokines were assessed. Additionally, metabolic parameters including body weight, fasting blood glucose (FBG), glucose & insulin tolerance, lipids profile, and leptin were measured. RESULTS HFD feeding resulted in impaired bone microarchitecture, reduced BMD, distorted bone histology, and altered bone turnover biomarkers as indicated by the significant reduction in bone ALP, BMP-2, osteocalcin, and an increase in sclerostin, TRAP, and serum calcium. Interestingly, treatment with linagliptin and its combination with metformin significantly reverted the impaired bone architecture, BMD, and positively modulated bone turnover biomarkers, while metformin alone did not exhibit any significant improvement. Further, HFD induced diabetes and metabolic abnormalities (including an increase in body weight, FBG, impaired glucose and insulin tolerance, leptin, triglycerides, cholesterol), and pro-inflammatory cytokines (TNF-alpha and IL-1β) were successfully reversed by treatment with linagliptin, metformin, and their combination. CONCLUSION Linagliptin and its combination with metformin successfully ameliorated diabetic osteoporosis in HFD-fed mice possibly through modulation of BMP-2 and sclerostin. The study provides the first evidence for the possible use of linagliptin and metformin combination for managing diabetic osteoporosis.
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Affiliation(s)
| | - Divya Vohora
- Neurobehavioral Pharmacology Laboratory, Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
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23
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Sebők J, Édel Z, Dembrovszky F, Farkas N, Török Z, Balogh G, Péter M, Papp I, Balogi Z, Nusser N, Péter I, Hooper P, Geiger P, Erőss B, Wittmann I, Váncsa S, Vigh L, Hegyi P. Effect of HEAT therapy in patiEnts with type 2 Diabetes mellitus (HEATED): protocol for a randomised controlled trial. BMJ Open 2022; 12:e062122. [PMID: 35820741 PMCID: PMC9277369 DOI: 10.1136/bmjopen-2022-062122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 07/01/2022] [Indexed: 11/14/2022] Open
Abstract
INTRODUCTION The burden of type 2 diabetes mellitus (T2DM) is increasing worldwide. Heat therapy has been found effective in improving glycaemic control. However, to date, there is a lack of randomised controlled studies investigating the efficacy of heat therapy in T2DM. Therefore, we aim to investigate whether heat therapy with natural thermal mineral water can improve glycaemic control in patients with T2DM. METHODS AND ANALYSIS The HEAT therapy in patiEnts with type 2 Diabetes mellitus (HEATED) Study is a single-centre, two-arm randomised controlled trial being conducted at Harkány Thermal Rehabilitation Centre in Hungary. Patients with T2DM will be randomly assigned to group A (bath sessions in 38°C natural thermal mineral water) and group B (baths in thermoneutral water (30°C-32°C)). Both groups will complete a maximum of 5 weekly visits, averaging 50-60 visits over the 12-week study. Each session will last 30 min, with a physical check-up before the bath. At baseline, patients' T2DM status will be investigated thoroughly. Possible microvascular and macrovascular complications of T2DM will be assessed with physical and laboratory examinations. The short form-36 questionnaire will assess the quality of life. Patients will also be evaluated at weeks 4, 8 and 12. The primary endpoint will be the change of glycated haemoglobin from baseline to week 12. An estimated 65 patients will be enrolled per group, with a sample size re-estimation at the enrolment of 50% of the calculated sample size. ETHICS AND DISSEMINATION The study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (818-2/2022/EÜIG). Written informed consent is required from all participants. We will disseminate our results to the medical community and will publish our results in peer-reviewed journals. TRIAL REGISTRATION NUMBER ClinicalTrials.gov, NCT05237219.
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Affiliation(s)
- Judit Sebők
- 2nd Department of Internal Medicine, University of Pecs Medical School, Pécs, Hungary
| | - Zsófia Édel
- 2nd Department of Internal Medicine, University of Pecs Medical School, Pécs, Hungary
| | - Fanni Dembrovszky
- Institute for Translational Medicine, Szentágothai Research Centre, University of Pecs Medical School, Pécs, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Nelli Farkas
- Institute for Translational Medicine, Szentágothai Research Centre, University of Pecs Medical School, Pécs, Hungary
- Institute of Bioanalysis, University of Pecs Medical School, Pécs, Hungary
| | | | | | | | | | - Zsolt Balogi
- Institute of Biochemistry and Medical Chemistry, University of Pecs Medical School, Pécs, Hungary
| | - Nóra Nusser
- Harkány Thermal Rehabilitation Centre, Harkány, Hungary
| | - Iván Péter
- Harkány Thermal Rehabilitation Centre, Harkány, Hungary
| | - Philip Hooper
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Paige Geiger
- Department of Molecular and Integrative Physiology, University of Kansas School of Medicine, Kansas City, Kansas, USA
| | - Bálint Erőss
- Institute for Translational Medicine, Szentágothai Research Centre, University of Pecs Medical School, Pécs, Hungary
- Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - István Wittmann
- 2nd Department of Internal Medicine, University of Pecs Medical School, Pécs, Hungary
| | - Szilárd Váncsa
- Institute for Translational Medicine, Szentágothai Research Centre, University of Pecs Medical School, Pécs, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | | | - Péter Hegyi
- Institute for Translational Medicine, Szentágothai Research Centre, University of Pecs Medical School, Pécs, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
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24
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Sugimoto S, Mena HA, Sansbury BE, Kobayashi S, Tsuji T, Wang CH, Yin X, Huang TL, Kusuyama J, Kodani SD, Darcy J, Profeta G, Pereira N, Tanzi RE, Zhang C, Serwold T, Kokkotou E, Goodyear LJ, Cypess AM, Leiria LO, Spite M, Tseng YH. Brown adipose tissue-derived MaR2 contributes to cold-induced resolution of inflammation. Nat Metab 2022; 4:775-790. [PMID: 35760872 PMCID: PMC9792164 DOI: 10.1038/s42255-022-00590-0] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 05/18/2022] [Indexed: 12/30/2022]
Abstract
Obesity induces chronic inflammation resulting in insulin resistance and metabolic disorders. Cold exposure can improve insulin sensitivity in humans and rodents, but the mechanisms have not been fully elucidated. Here, we find that cold resolves obesity-induced inflammation and insulin resistance and improves glucose tolerance in diet-induced obese mice. The beneficial effects of cold exposure on improving obesity-induced inflammation and insulin resistance depend on brown adipose tissue (BAT) and liver. Using targeted liquid chromatography with tandem mass spectrometry, we discovered that cold and β3-adrenergic stimulation promote BAT to produce maresin 2 (MaR2), a member of the specialized pro-resolving mediators of bioactive lipids that play a role in the resolution of inflammation. Notably, MaR2 reduces inflammation in obesity in part by targeting macrophages in the liver. Thus, BAT-derived MaR2 could contribute to the beneficial effects of BAT activation in resolving obesity-induced inflammation and may inform therapeutic approaches to combat obesity and its complications.
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Affiliation(s)
- Satoru Sugimoto
- Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Hebe Agustina Mena
- Department of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Brian E Sansbury
- Department of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Shio Kobayashi
- Section of Immunobiology, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Tadataka Tsuji
- Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Chih-Hao Wang
- Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Xuanzhi Yin
- Department of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Tian Lian Huang
- Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Joji Kusuyama
- Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Sean D Kodani
- Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Justin Darcy
- Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Gerson Profeta
- Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Nayara Pereira
- Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Rudolph E Tanzi
- Genetics and Aging Research Unit, McCance Center for Brain Health, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Can Zhang
- Genetics and Aging Research Unit, McCance Center for Brain Health, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Thomas Serwold
- Section of Immunobiology, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Efi Kokkotou
- Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Laurie J Goodyear
- Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Aaron M Cypess
- Diabetes, Endocrinology, and Obesity Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD, USA
| | - Luiz Osório Leiria
- Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
- Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Matthew Spite
- Department of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
| | - Yu-Hua Tseng
- Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
- Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
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25
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Alyahya AM. The role of progranulin in ischemic heart disease and its related risk factors. Eur J Pharm Sci 2022; 175:106215. [DOI: 10.1016/j.ejps.2022.106215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 04/23/2022] [Accepted: 05/20/2022] [Indexed: 11/15/2022]
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VerHague M, Albright J, Barron K, Kim M, Bennett BJ. Obesogenic and diabetic effects of CD44 in mice are sexually dimorphic and dependent on genetic background. Biol Sex Differ 2022; 13:14. [PMID: 35410390 PMCID: PMC8996418 DOI: 10.1186/s13293-022-00426-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 03/29/2022] [Indexed: 11/30/2022] Open
Abstract
Introduction CD44 is a candidate gene for obesity and diabetes development and may be a critical mediator of a systemic inflammation associated with obesity and diabetes. Methods We investigated the relationship of CD44 with obesity in CD44-deficient mice challenged with a high-fat diet. Results In mice fed a diet high in fat, cholesterol, and sucrose for 12 weeks fat mass accumulation was reduced in CD44-deficient mice bred onto both a C57BL/6J and the naturally TLR deficient C3H/HeJ background. Reduced fat mass could not be attributed to lower food intake or an increase in energy expenditure as measured by indirect calorimetry. However, we observed a 40–60% lower mRNA expression of the inflammation markers, F4/80, CD11b, TNF-α, and CD14, in adipose tissue of CD44-deficient mice on the C57BL/6J background but not the C3H/HeJ background, perhaps indicating that alternative factors may be affecting adiposity in this model. Measures of hepatic steatosis and insulin sensitivity were improved in CD44-deficient mice on a C57BL/6J but not in the C3H/HeJ mice. These results were highly sexually dimorphic as there were no detectable effects of CD44 inactivation in female mice on a C57BL/6 J or C3H/HeJ background. Conclusion CD44 was associated with adiposity, liver fat, and glucose in male mice. However, the effects of CD44 on obesity may be independent of TLR4 signaling. Supplementary Information The online version contains supplementary material available at 10.1186/s13293-022-00426-2.
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Affiliation(s)
- Melissa VerHague
- Nutrition Research Institute, University of North Carolina Kannapolis, Kannapolis, NC, 28081, USA
| | - Jody Albright
- Nutrition Research Institute, University of North Carolina Kannapolis, Kannapolis, NC, 28081, USA
| | - Keri Barron
- Nutrition Research Institute, University of North Carolina Kannapolis, Kannapolis, NC, 28081, USA
| | - Myungsuk Kim
- Department of Nutrition, University of California, Davis, 95616, USA.,Korea Institute of Science and Technology (KIST), Gangneung, Gangwon-do, Republic of Korea
| | - Brian J Bennett
- Obesity and Metabolism Research Unit USDA, ARS Western Human Nutrition Research Center, 430 W Health Sciences Drive, Davis, CA, 95616, USA. .,Department of Nutrition, University of California, Davis, 95616, USA.
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Ondaro J, Hernandez-Eguiazu H, Garciandia-Arcelus M, Loera-Valencia R, Rodriguez-Gómez L, Jiménez-Zúñiga A, Goikolea J, Rodriguez-Rodriguez P, Ruiz-Martinez J, Moreno F, Lopez de Munain A, Holt IJ, Gil-Bea FJ, Gereñu G. Defects of Nutrient Signaling and Autophagy in Neurodegeneration. Front Cell Dev Biol 2022; 10:836196. [PMID: 35419363 PMCID: PMC8996160 DOI: 10.3389/fcell.2022.836196] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 02/21/2022] [Indexed: 12/27/2022] Open
Abstract
Neurons are post-mitotic cells that allocate huge amounts of energy to the synthesis of new organelles and molecules, neurotransmission and to the maintenance of redox homeostasis. In neurons, autophagy is not only crucial to ensure organelle renewal but it is also essential to balance nutritional needs through the mobilization of internal energy stores. A delicate crosstalk between the pathways that sense nutritional status of the cell and the autophagic processes to recycle organelles and macronutrients is fundamental to guarantee the proper functioning of the neuron in times of energy scarcity. This review provides a detailed overview of the pathways and processes involved in the balance of cellular energy mediated by autophagy, which when defective, precipitate the neurodegenerative cascade of Parkinson's disease, frontotemporal dementia, amyotrophic lateral sclerosis or Alzheimer's disease.
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Affiliation(s)
- Jon Ondaro
- Department of Neuroscience, Biodonostia Health Research Institute (IIS Biodonostia), San Sebastian, Spain
- Center for Biomedical Research of Neurodegenerative Diseases (CIBERNED), Madrid, Spain
| | - Haizea Hernandez-Eguiazu
- Department of Neuroscience, Biodonostia Health Research Institute (IIS Biodonostia), San Sebastian, Spain
- Center for Biomedical Research of Neurodegenerative Diseases (CIBERNED), Madrid, Spain
| | - Maddi Garciandia-Arcelus
- Department of Neuroscience, Biodonostia Health Research Institute (IIS Biodonostia), San Sebastian, Spain
- Center for Biomedical Research of Neurodegenerative Diseases (CIBERNED), Madrid, Spain
| | - Raúl Loera-Valencia
- Department of Neurology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet (KI), Stockholm, Sweden
| | - Laura Rodriguez-Gómez
- Department of Neuroscience, Biodonostia Health Research Institute (IIS Biodonostia), San Sebastian, Spain
- Center for Biomedical Research of Neurodegenerative Diseases (CIBERNED), Madrid, Spain
| | - Andrés Jiménez-Zúñiga
- Department of Neuroscience, Biodonostia Health Research Institute (IIS Biodonostia), San Sebastian, Spain
- Center for Biomedical Research of Neurodegenerative Diseases (CIBERNED), Madrid, Spain
| | - Julen Goikolea
- Department of Neurology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet (KI), Stockholm, Sweden
| | - Patricia Rodriguez-Rodriguez
- Department of Neurology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet (KI), Stockholm, Sweden
| | - Javier Ruiz-Martinez
- Department of Neuroscience, Biodonostia Health Research Institute (IIS Biodonostia), San Sebastian, Spain
- Center for Biomedical Research of Neurodegenerative Diseases (CIBERNED), Madrid, Spain
- Donostia University Hospital, San Sebastian, Spain
| | - Fermín Moreno
- Department of Neuroscience, Biodonostia Health Research Institute (IIS Biodonostia), San Sebastian, Spain
- Center for Biomedical Research of Neurodegenerative Diseases (CIBERNED), Madrid, Spain
- Donostia University Hospital, San Sebastian, Spain
| | - Adolfo Lopez de Munain
- Department of Neuroscience, Biodonostia Health Research Institute (IIS Biodonostia), San Sebastian, Spain
- Center for Biomedical Research of Neurodegenerative Diseases (CIBERNED), Madrid, Spain
- Donostia University Hospital, San Sebastian, Spain
| | - Ian James Holt
- Department of Neuroscience, Biodonostia Health Research Institute (IIS Biodonostia), San Sebastian, Spain
- Center for Biomedical Research of Neurodegenerative Diseases (CIBERNED), Madrid, Spain
- Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, United Kingdom
- IKERBASQUE Basque Foundation for Science, Bilbao, Spain
| | - Francisco Javier Gil-Bea
- Department of Neuroscience, Biodonostia Health Research Institute (IIS Biodonostia), San Sebastian, Spain
- Center for Biomedical Research of Neurodegenerative Diseases (CIBERNED), Madrid, Spain
| | - Gorka Gereñu
- Department of Neuroscience, Biodonostia Health Research Institute (IIS Biodonostia), San Sebastian, Spain
- Center for Biomedical Research of Neurodegenerative Diseases (CIBERNED), Madrid, Spain
- Department of Physiology, Faculty of Medicine and Nursing, University of Basque Country (UPV-EHU), Leioa, Spain
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Kreiner FF, Kraaijenhof JM, von Herrath M, Hovingh GKK, von Scholten BJ. Interleukin 6 in diabetes, chronic kidney disease and cardiovascular disease: mechanisms and therapeutic perspectives. Expert Rev Clin Immunol 2022; 18:377-389. [PMID: 35212585 DOI: 10.1080/1744666x.2022.2045952] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Diabetes, chronic kidney disease (CKD) and cardiovascular disease (CVD) are cardiometabolic diseases that remain amongst the leading causes of morbidity and premature mortality. Here, we review the current understanding of how anti-inflammatory intervention via inhibition of the pro-inflammatory but pleiotropic cytokine interleukin (IL) 6 may benefit patients with these or related diseases or complications. AREAS COVERED Based on a PubMed literature search, this review integrates and contextualizes evidence regarding the clinical utility of anti-IL-6 intervention in the treatment of cardiometabolic diseases, as well as of the associated condition non-alcoholic hepatosteatosis. EXPERT OPINION Evidence implicates the pro-inflammatory effects of IL-6 in the pathophysiology of diabetes, CKD and CVD. Thus, targeting the IL-6 pathway holds a therapeutic potential in these cardiometabolic disorders. However, because IL-6 has multiple homeostatic roles, antagonizing this cytokine may be associated with side effects such as increased risk of infection as seen with other anti-inflammatory drugs. Additional studies are required to establish the benefit-risk profile of anti-IL-6 intervention in the cardiometabolic diseases, whilst also considering alternative interventions such as lifestyle changes. IL-6 is also elevated in NASH, but the clinical usefulness of targeting IL-6 in this hepatic disorder remains largely unexplored.
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Affiliation(s)
| | - Jordan M Kraaijenhof
- Global Chief Medical Office, Novo Nordisk A/S, Søborg, Denmark.,Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Matthias von Herrath
- Global Chief Medical Office, Novo Nordisk A/S, Søborg, Denmark.,La Jolla Institute for Immunology, La Jolla, California, United States
| | - G Kees Kornelis Hovingh
- Global Chief Medical Office, Novo Nordisk A/S, Søborg, Denmark.,Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands
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29
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Sarcopenia Is Associated with Metabolic Syndrome in Korean Adults Aged over 50 Years: A Cross-Sectional Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19031330. [PMID: 35162353 PMCID: PMC8835141 DOI: 10.3390/ijerph19031330] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 01/20/2022] [Accepted: 01/24/2022] [Indexed: 11/16/2022]
Abstract
This study assessed the association between sarcopenia and metabolic syndrome in Korean adults aged over 50 years. The study obtained data from the Korea National Health and Nutrition Examination Survey (KNHANES, 2008–2011), a cross-sectional and nationally representative survey conducted by the Korean Centers for Disease Control and Prevention. Among the 8363 participants included in this study, the prevalence rate of sarcopenia according to metabolic syndrome was stratified by sex. Crude odds ratios not adjusted for any variables were 1.827 (1.496–2.231) in males, 2.189 (1.818–2.635) in females, and 2.209 (1.766–2.331) in total participants compared with non-sarcopenia. Model 3, which was adjusted for all variables that could affect sarcopenia and metabolic syndrome, showed significant increases in the odds ratios, to 1.957 (1.587–2.413) in males, 1.779 (1.478–2.141) in females, and 1.822 (1.586–2.095) for total participants. The results suggest that the association between sarcopenia and metabolic syndrome is significant in Korean adults.
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30
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Azevedo RB, Wandermurem DC, Libório FC, Machado MK, Ushijima NM, Narde RS, Pecly IMD, Muxfeldt ES. Impact of Metabolic Risk Factors on COVID-19 Clinical Outcomes: An Extensive Review. Curr Cardiol Rev 2022; 18:e090522204452. [PMID: 35579126 PMCID: PMC9893150 DOI: 10.2174/1573403x18666220509154236] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 02/11/2022] [Accepted: 02/24/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Cardiovascular (CV) risk factors, particularly cardiometabolic, seem to be associated with heightened severity and increased morbimortality in patients infected with the novel Coronavirus disease-2019 (COVID-19). METHODS A thorough scoping review was conducted to elucidate and summarize the latest evidence for the effects of adverse cardiac metabolic profiles on the severity, morbidity, and prognosis of COVID-19 infection. RESULTS The pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is complex, being characterized by viral-induced immune dysregulation and hypercytokinemia, particularly in patients with critical disease, evolving with profound endothelial dysfunction, systemic inflammation, and prothrombotic state. Moreover, cardiovascular comorbidities such as diabetes are the most prevalent amongst individuals requiring hospitalization, raising concerns towards the clinical evolution and prognosis of these patients. The chronic proinflammatory state observed in patients with cardiovascular risk factors may contribute to the immune dysregulation mediated by SARS-CoV-2, favoring more adverse clinical outcomes and increased severity. Cardiometabolism is defined as a combination of interrelated risk factors and metabolic dysfunctions such as dyslipidemia, insulin resistance, impaired glucose tolerance, and central adiposity, which increase the likelihood of vascular events, being imperative to specifically analyze its clinical association with COVID-19 outcomes. CONCLUSION DM and obesity appears to be important risk factors for severe COVID-19. The chronic proinflammatory state observed in patients with excess visceral adipose tissue (VAT) possibly augments COVID-19 immune hyperactivity leading to more adverse clinical outcomes in these patients.
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Affiliation(s)
- Rafael B. Azevedo
- Medicine Course, IDOMED - Universidade Estácio de Sá - Campus Presidente Vargas, Rio de Janeiro, Brazil
| | - Débora C.R. Wandermurem
- Medicine Course, IDOMED - Universidade Estácio de Sá - Campus Presidente Vargas, Rio de Janeiro, Brazil
| | - Flávia C.F. Libório
- Medicine Course, IDOMED - Universidade Estácio de Sá - Campus Presidente Vargas, Rio de Janeiro, Brazil
| | - Maíra K. Machado
- Medicine Course, IDOMED - Universidade Estácio de Sá - Campus Presidente Vargas, Rio de Janeiro, Brazil
| | - Natália M. Ushijima
- Medicine Course, IDOMED - Universidade Estácio de Sá - Campus Presidente Vargas, Rio de Janeiro, Brazil
| | - Ramon S. Narde
- Medicine Course, IDOMED - Universidade Estácio de Sá - Campus Presidente Vargas, Rio de Janeiro, Brazil
| | - Inah Maria D. Pecly
- Medicine Course, IDOMED - Universidade Estácio de Sá - Campus Presidente Vargas, Rio de Janeiro, Brazil
| | - Elizabeth S. Muxfeldt
- Medicine Course, IDOMED - Universidade Estácio de Sá - Campus Presidente Vargas, Rio de Janeiro, Brazil
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31
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Chen HH, Petty LE, North KE, McCormick JB, Fisher-Hoch SP, Gamazon ER, Below JE. OUP accepted manuscript. Hum Mol Genet 2022; 31:3191-3205. [PMID: 35157052 PMCID: PMC9476627 DOI: 10.1093/hmg/ddac039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 01/17/2022] [Accepted: 01/18/2022] [Indexed: 11/17/2022] Open
Abstract
Type 2 diabetes is a complex, systemic disease affected by both genetic and environmental factors. Previous research has identified genetic variants associated with type 2 diabetes risk; however, gene regulatory changes underlying progression to metabolic dysfunction are still largely unknown. We investigated RNA expression changes that occur during diabetes progression using a two-stage approach. In our discovery stage, we compared changes in gene expression using two longitudinally collected blood samples from subjects whose fasting blood glucose transitioned to a level consistent with type 2 diabetes diagnosis between the time points against those who did not with a novel analytical network approach. Our network methodology identified 17 networks, one of which was significantly associated with transition status. This 822-gene network harbors many genes novel to the type 2 diabetes literature but is also significantly enriched for genes previously associated with type 2 diabetes. In the validation stage, we queried associations of genetically determined expression with diabetes-related traits in a large biobank with linked electronic health records. We observed a significant enrichment of genes in our identified network whose genetically determined expression is associated with type 2 diabetes and other metabolic traits and validated 31 genes that are not near previously reported type 2 diabetes loci. Finally, we provide additional functional support, which suggests that the genes in this network are regulated by enhancers that operate in human pancreatic islet cells. We present an innovative and systematic approach that identified and validated key gene expression changes associated with type 2 diabetes transition status and demonstrated their translational relevance in a large clinical resource.
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Affiliation(s)
- Hung-Hsin Chen
- Vanderbilt Genetics Institute and Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Lauren E Petty
- Vanderbilt Genetics Institute and Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Kari E North
- Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Joseph B McCormick
- The University of Texas Health Science Center at Houston (UTHealth) School of Public Health, Brownsville, TX 78520, USA
| | - Susan P Fisher-Hoch
- The University of Texas Health Science Center at Houston (UTHealth) School of Public Health, Brownsville, TX 78520, USA
| | - Eric R Gamazon
- Vanderbilt Genetics Institute and Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Clare Hall, University of Cambridge, Cambridgeshire, UK
| | - Jennifer E Below
- To whom correspondence should be addressed. Tel: +1-615-343-1655;
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32
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Abstract
Two decades of research have established that Nuclear Factor-κB (NF-κB) signaling plays a critical role in reprogramming the fat cell transcriptome towards inflammation in response to overnutrition and metabolic stress. Several groups have suggested that inhibition of NF-κB signaling could have metabolic benefits for obesity-associated adipose tissue inflammation. However, two significant problems arise with this approach. The first is how to deliver general NF-κB inhibitors into adipocytes without allowing these compounds to disrupt normal functioning in cells of the immune system. The second issue is that general inhibition of canonical NF-κB signaling in adipocytes will likely lead to a massive increase in adipocyte apoptosis under conditions of metabolic stress, leading full circle into a secondary inflammation (However, this problem may not be true for non-canonical NF-κB signaling.). This review will focus on the research that has examined canonical and non-canonical NF-κB signaling in adipocytes, focusing on genetic studies that examine loss-of-function of NF-κB specifically in fat cells. Although the development of general inhibitors of canonical NF-κB signaling seems unlikely to succeed in alleviating adipose tissue inflammation in humans, the door remains open for more targeted therapeutics. In principle, these would include compounds that interrogate NF-κB DNA binding, protein-protein interactions, or post-translational modifications that partition NF-κB activity towards some genes and away from others in adipocytes. I also discuss the possibility for inhibitors of non-canonical NF-κB signaling to realize success in mitigating fat cell dysfunction in obesity. To plant the seeds for such approaches, much biochemical “digging” in adipocytes remains; this includes identifying—in an unbiased manner–NF-κB direct and indirect targets, genomic DNA binding sites for all five NF-κB subunits, NF-κB protein-protein interactions, and post-translational modifications of NF-κB in fat cells.
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33
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Li J, Chen Q, Zhai X, Wang D, Hou Y, Tang M. Green tea aqueous extract (GTAE) prevents high-fat diet-induced obesity by activating fat browning. Food Sci Nutr 2021; 9:6548-6558. [PMID: 34925784 PMCID: PMC8645728 DOI: 10.1002/fsn3.2580] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 08/19/2021] [Accepted: 08/22/2021] [Indexed: 11/08/2022] Open
Abstract
Adipose browning leads to increased energy expenditure and reduced adiposity and has, therefore, become an attractive therapeutic strategy for obesity. In this study, we elucidated the effect of green tea aqueous extract (GTAE) on the browning of inguinal white adipose tissue (Ing-WAT) and brown adipose tissue (BAT) in high-fat diet (HFD)-fed mice. The main phytochemical components identified in GTAE through high-performance liquid chromatography (HPLC) included (-)-gallocatechin, (-)-epigallocatechin, (-)-catechin, (-)-epigallocatechin-3-gallate, caffeine, (-)-epicatechin, (-)-gallocatechin gallate, and (-)-epicatechin-3-gallate. Daily supplementation with 1% GTAE for 12 weeks markedly reduced bodyweight gain, systemic inflammation, oxidative stress, and improved insulin resistance. Additionally, histological analysis revealed that dietary supplementation with 1% GTAE reversed HFD-induced adipocyte size and hepatic steatosis. These effects were associated with activation of browning in the Ing-WAT and BAT, which mediate systemic metabolic dysfunction in HFD-fed mice. Taken together, our data support the use of GTAE, a natural product, for the attenuation of obesity through the activation of fat browning.
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Affiliation(s)
- Jie Li
- Research Institute of TeaChongqing Academy of Agricultural SciencesChongqingChina
| | - Qiyang Chen
- College of Horticulture and Landscape ArchitectureSouthwest UniversityChongqingChina
| | - Xiuming Zhai
- Research Institute of TeaChongqing Academy of Agricultural SciencesChongqingChina
| | - Dan Wang
- College of Horticulture and Landscape ArchitectureSouthwest UniversityChongqingChina
| | - Yujia Hou
- Research Institute of TeaChongqing Academy of Agricultural SciencesChongqingChina
| | - Min Tang
- Research Institute of TeaChongqing Academy of Agricultural SciencesChongqingChina
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34
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Gemperle C, Tran S, Schmid M, Rimann N, Marti-Jaun J, Hartling I, Wawrzyniak P, Hersberger M. Resolvin D1 reduces inflammation in co-cultures of primary human macrophages and adipocytes by triggering macrophages. Prostaglandins Leukot Essent Fatty Acids 2021; 174:102363. [PMID: 34740032 DOI: 10.1016/j.plefa.2021.102363] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 10/04/2021] [Accepted: 10/27/2021] [Indexed: 12/21/2022]
Abstract
Obesity leads to chronic inflammation of the adipose tissue which is tightly associated with the metabolic syndrome, type 2 diabetes and cardiovascular disease. Inflammation of the adipose tissue is mainly characterized by the presence of crown-like structures composed of inflammatory macrophages in the neighborhood of adipocytes. Resolvin D1 (RvD1), a potent anti-inflammatory and pro-resolving lipid mediator derived from the omega-3 fatty acid docosahexaenoic acid, has been shown to reduce the inflammatory tone of adipose tissue in animal models but the underlying mechanism is not clear. We investigated the effect of RvD1 on the inflammatory state of a human co-culture system of adipocytes and macrophages. For this, human mesenchymal stem cells were differentiated into mature adipocytes and overlaid with human primary macrophages. In this co-culture, 10-500 nM RvD1 dose-dependently reduced the secretion of the pro-inflammatory cytokine IL-6 (-21%) and its soluble receptor IL-6Rα (-22%), of the chemokine MCP-1 (-13%), and of the adipokine leptin (-22%). Similarly, we observed a reduction in secretion of the soluble receptor IL-6Rα (-20%), and TNF-α (-11%) when macrophages alone were treated with RvD1, while no change of cytokine secretion was observed when adipocytes were treated with RvD1. We conclude that RvD1 polarizes macrophages to an anti-inflammatory phenotype, which in turn modulates inflammation in adipocytes.
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Affiliation(s)
- Claudio Gemperle
- Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland
| | - Syndi Tran
- Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland
| | - Mattia Schmid
- Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland
| | - Nicole Rimann
- Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland
| | - Jacqueline Marti-Jaun
- Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland
| | - Ivan Hartling
- Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland; Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
| | - Paulina Wawrzyniak
- Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland
| | - Martin Hersberger
- Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland; Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
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35
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Hsu CH, Chen YL, Hsieh CH, Liang YJ, Liu SH, Pei D. Hemogram-based decision tree for predicting the metabolic syndrome and cardiovascular diseases in the elderly. QJM 2021; 114:363-373. [PMID: 32573729 DOI: 10.1093/qjmed/hcaa205] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 05/17/2020] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND This study aimed to build a hemogram-based decision tree to evaluate the association between current probability of metabolic syndrome (MetS) and prediction of future hypertension, type 2 diabetes and cardiovascular diseases (CVD) risk. METHODS A total of 40 395 elder participants (≥60 years) were enrolled in a standard health examination program in Taiwan from January 1999 to December 2014. A decision tree classification of the presence or absence of MetS at baseline, using age, sex and hemogram (white blood cell, hemoglobin and platelet) as independent variables, was conducted for the randomly assigned training (70%) and validation (30%) groups. Participants without MetS at baseline (n = 25 643) were followed up to observe whether they developed MetS, hypertension, type 2 diabetes or CVD in the future. RESULTS Modest accuracy of the decision tree in the training and validation groups with area under the curves of 0.653 and 0.652, respectively, indicated an acceptable generalizability of results. The predicted probability of baseline MetS was obtained from decision tree analysis. Participants without MetS at baseline were categorized into three equally sized groups according to the predicted probability. Participants in the third tertile had significantly higher risks of future MetS (hazard ratio 1.40, 95% confidence interval 1.25-1.58); type 2 diabetes (1.46, 1.17-1.83); hypertension (1.14, 1.01-1.28); and CVD (1.21, 1.01-1.44), compared with those in the first tertile. CONCLUSIONS Execution of hemogram-based decision tree analysis can assist in early identification and prompt management of elderly patients at a high risk of future hypertension, type 2 diabetes and CVD.
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Affiliation(s)
- C-H Hsu
- From the Department of Family Medicine
- Department of Geriatric Medicine, Center for Geriatrics and Gerontology, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wenchang Rd., Shilin Dist., Taipei City 111, Taiwan
- Department of Family Medicine, Cardinal Tien Hospital, No.362, Zhongzheng Rd., Xindian Dist., New Taipei City 231, Taiwan
- School of Medicine, College of Medicine, Fu Jen Catholic University, 510 Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242, Taiwan
| | - Y-L Chen
- School of Medicine, College of Medicine, Fu Jen Catholic University, 510 Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242, Taiwan
- Department of Pathology, Cardinal Tien Hospital, No.362, Zhongzheng Rd., Xindian Dist., New Taipei City 231, Taiwan
| | - C-H Hsieh
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chenggong Rd., Neihu Dist., Taipei City 114, Taiwan
| | - Y-J Liang
- Department of Life Science, Graduate Institute of Applied Science and Engineering, College of Science and Engineering, Fu Jen Catholic University, 510 Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242, Taiwan
| | - S-H Liu
- School of Nursing, College of Nursing, National Taipei University of Nursing and Health Science, No. 365, Mingde Rd., Beitou Dist., Taipei City 112, Taiwan
| | - D Pei
- School of Medicine, College of Medicine, Fu Jen Catholic University, 510 Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242, Taiwan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Fu Jen Catholic University Hospital, No. 69, Guizi Rd., Taishan Dist., New Taipei City 243, Taiwan
- Department of Internal Medicine, Cardinal Tien Hospital, No.362, Zhongzheng Rd., Xindian Dist., New Taipei City 231, Taiwan
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Gissler MC, Anto-Michel N, Pennig J, Scherrer P, Li X, Marchini T, Pfeiffer K, Härdtner C, Abogunloko T, Mwinyella T, Sol Mitre L, Spiga L, Koentges C, Smolka C, von Elverfeldt D, Hoppe N, Stachon P, Dufner B, Heidt T, Piepenburg S, Hilgendorf I, Bjune JI, Dankel SN, Mellgren G, Seifert G, Eisenhardt SU, Bugger H, von Zur Muhlen C, Bode C, Zirlik A, Wolf D, Willecke F. Genetic Deficiency of TRAF5 Promotes Adipose Tissue Inflammation and Aggravates Diet-Induced Obesity in Mice. Arterioscler Thromb Vasc Biol 2021; 41:2563-2574. [PMID: 34348490 DOI: 10.1161/atvbaha.121.316677] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Objective: The accumulation of inflammatory leukocytes is a prerequisite of adipose tissue inflammation during cardiometabolic disease. We previously reported that a genetic deficiency of the intracellular signaling adaptor TRAF5 (TNF [tumor necrosis factor] receptor-associated factor 5) accelerates atherosclerosis in mice by increasing inflammatory cell recruitment. Here, we tested the hypothesis that an impairment of TRAF5 signaling modulates adipose tissue inflammation and its metabolic complications in a model of diet-induced obesity in mice. Approach and Results: To induce diet-induced obesity and adipose tissue inflammation, wild-type or Traf5-/- mice consumed a high-fat diet for 18 weeks. Traf5-/- mice showed an increased weight gain, impaired insulin tolerance, and increased fasting blood glucose. Weight of livers and peripheral fat pads was increased in Traf5-/- mice, whereas lean tissue weight and growth were not affected. Flow cytometry of the stromal vascular fraction of visceral adipose tissue from Traf5-/- mice revealed an increase in cytotoxic T cells, CD11c+ macrophages, and increased gene expression of proinflammatory cytokines and chemokines. At the level of cell types, expression of TNF[alpha], MIP (macrophage inflammatory protein)-1[alpha], MCP (monocyte chemoattractant protein)-1, and RANTES (regulated on activation, normal T-cell expressed and secreted) was significantly upregulated in Traf5-deficient adipocytes but not in Traf5-deficient leukocytes from visceral adipose tissue. Finally, Traf5 expression was lower in adipocytes from obese patients and mice and recovered in adipose tissue of obese patients one year after bariatric surgery. Conclusions: We show that a genetic deficiency of TRAF5 in mice aggravates diet-induced obesity and its metabolic derangements by a proinflammatory response in adipocytes. Our data indicate that TRAF5 may promote anti-inflammatory and obesity-preventing signaling events in adipose tissue.
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Affiliation(s)
- Mark Colin Gissler
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Nathaly Anto-Michel
- Department of Cardiology, Medical University of Graz, Austria (N.A.M., H.B., A.Z.)
| | - Jan Pennig
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Philipp Scherrer
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Xiaowei Li
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Timoteo Marchini
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Katharina Pfeiffer
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Carmen Härdtner
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Tijani Abogunloko
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Timothy Mwinyella
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Lucia Sol Mitre
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Lisa Spiga
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Christoph Koentges
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
- Institute of Neuropathology (C.K.), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
| | - Christian Smolka
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Dominik von Elverfeldt
- Department of Radiology, Medical Physics (D.v.E.), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
| | - Natalie Hoppe
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Peter Stachon
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Bianca Dufner
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Timo Heidt
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Sven Piepenburg
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Ingo Hilgendorf
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Jan-Inge Bjune
- Center for Diabetes Research (J.-I.B., S.N.D., G.M.), University of Bergen, Norway
- Mohn Nutrition Research Laboratory, Department of Clinical Science (J.-I.B., S.N.D., G.M.), University of Bergen, Norway
- Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway (J.-I.B., S.N.D., G.M.)
| | - Simon N Dankel
- Center for Diabetes Research (J.-I.B., S.N.D., G.M.), University of Bergen, Norway
- Mohn Nutrition Research Laboratory, Department of Clinical Science (J.-I.B., S.N.D., G.M.), University of Bergen, Norway
- Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway (J.-I.B., S.N.D., G.M.)
| | - Gunnar Mellgren
- Center for Diabetes Research (J.-I.B., S.N.D., G.M.), University of Bergen, Norway
- Mohn Nutrition Research Laboratory, Department of Clinical Science (J.-I.B., S.N.D., G.M.), University of Bergen, Norway
- Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway (J.-I.B., S.N.D., G.M.)
| | - Gabriel Seifert
- Department of General and Visceral Surgery (G.S.), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
| | - Steffen U Eisenhardt
- Department of Plastic and Hand Surgery, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany (S.U.E.)
| | - Heiko Bugger
- Department of Cardiology, Medical University of Graz, Austria (N.A.M., H.B., A.Z.)
| | - Constantin von Zur Muhlen
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Christoph Bode
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Andreas Zirlik
- Department of Cardiology, Medical University of Graz, Austria (N.A.M., H.B., A.Z.)
| | - Dennis Wolf
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
| | - Florian Willecke
- Cardiology and Angiology I, University Heart Center, Faculty of Medicine, University of Freiburg, Germany (M.C.G., J.P., P.S., X.L., T. Marchini, K.P., C.H., T.A., T. Mwinyella, L.S.M., L.S., C.K., C.S., N.H., P.S., B.D., T.H., S.P., I.H., C.v.z.M., C.B., D.W., F.W.)
- Clinic for General and Interventional Cardiology/Angiology, Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany (F.W.)
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Adipose Tissue Macrophages Modulate Obesity-Associated β Cell Adaptations through Secreted miRNA-Containing Extracellular Vesicles. Cells 2021; 10:cells10092451. [PMID: 34572101 PMCID: PMC8472266 DOI: 10.3390/cells10092451] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 09/07/2021] [Accepted: 09/14/2021] [Indexed: 12/19/2022] Open
Abstract
Obesity induces an adaptive expansion of β cell mass and insulin secretion abnormality. Expansion of adipose tissue macrophages (ATMs) is a hallmark of obesity. Here, we assessed a novel role of ATMs in mediating obesity-induced β cell adaptation through the release of miRNA-containing extracellular vesicles (EVs). In both in vivo and in vitro experiments, we show that ATM EVs derived from obese mice notably suppress insulin secretion and enhance β cell proliferation. We also observed similar phenotypes from human islets after obese ATM EV treatment. Importantly, depletion of miRNAs blunts the effects of obese ATM EVs, as evidenced by minimal effects of obese DicerKO ATM EVs on β cell responses. miR-155 is a highly enriched miRNA within obese ATM EVs and miR-155 overexpressed in β cells impairs insulin secretion and enhances β cell proliferation. In contrast, knockout of miR-155 attenuates the regulation of obese ATM EVs on β cell responses. We further demonstrate that the miR-155-Mafb axis plays a critical role in controlling β cell responses. These studies show a novel mechanism by which ATM-derived EVs act as endocrine vehicles delivering miRNAs and subsequently mediating obesity-associated β cell adaptation and dysfunction.
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Ji Y, Luo Z, Gao H, Dos Reis FCG, Bandyopadhyay G, Jin Z, Manda KA, Isaac R, Yang M, Fu W, Ying W, Olefsky JM. Hepatocyte-derived exosomes from early onset obese mice promote insulin sensitivity through miR-3075. Nat Metab 2021; 3:1163-1174. [PMID: 34489604 PMCID: PMC8460610 DOI: 10.1038/s42255-021-00444-1] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023]
Abstract
In chronic obesity, hepatocytes become insulin resistant and exert important effects on systemic metabolism. Here we show that in early onset obesity (4 weeks high-fat diet), hepatocytes secrete exosomes that enhance insulin sensitivity both in vitro and in vivo. These beneficial effects were due to exosomal microRNA miR-3075, which is enriched in these hepatocyte exosomes. FA2H is a direct target of miR-3075 and small interfering RNA depletion of FA2H in adipocytes, myocytes and primary hepatocytes leads to increased insulin sensitivity. In chronic obesity (16-18 weeks of a high-fat diet), hepatocyte exosomes promote a state of insulin resistance. These chronic obese hepatocyte exosomes do not directly cause impaired insulin signalling in vitro but do promote proinflammatory activation of macrophages. Taken together, these studies show that in early onset obesity, hepatocytes produce exosomes that express high levels of the insulin-sensitizing miR-3075. In chronic obesity, this compensatory effect is lost and hepatocyte-derived exosomes from chronic obese mice promote insulin resistance.
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Affiliation(s)
- Yudong Ji
- Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, CA, USA
- Department of Anesthesiology, Institute of Anesthesiology and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhenlong Luo
- Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, CA, USA
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hong Gao
- Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, CA, USA
| | | | - Gautam Bandyopadhyay
- Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, CA, USA
| | - Zhongmou Jin
- Division of Biological Sciences, University of California, San Diego, CA, USA
| | | | - Roi Isaac
- Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, CA, USA
| | - Meixiang Yang
- Pediatric Diabetes Research Center, Department of Pediatrics, University of California, San Diego, CA, USA
- Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, the Biomedical Translational Research Institute, Jinan University, Guangzhou, China
| | - Wenxian Fu
- Pediatric Diabetes Research Center, Department of Pediatrics, University of California, San Diego, CA, USA
- Department of Cancer Immunology, Genentech, San Francisco, CA, USA
| | - Wei Ying
- Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, CA, USA.
| | - Jerrold M Olefsky
- Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, CA, USA.
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Guerra JVS, Dias MMG, Brilhante AJVC, Terra MF, García-Arévalo M, Figueira ACM. Multifactorial Basis and Therapeutic Strategies in Metabolism-Related Diseases. Nutrients 2021; 13:nu13082830. [PMID: 34444990 PMCID: PMC8398524 DOI: 10.3390/nu13082830] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 08/09/2021] [Accepted: 08/11/2021] [Indexed: 12/11/2022] Open
Abstract
Throughout the 20th and 21st centuries, the incidence of non-communicable diseases (NCDs), also known as chronic diseases, has been increasing worldwide. Changes in dietary and physical activity patterns, along with genetic conditions, are the main factors that modulate the metabolism of individuals, leading to the development of NCDs. Obesity, diabetes, metabolic associated fatty liver disease (MAFLD), and cardiovascular diseases (CVDs) are classified in this group of chronic diseases. Therefore, understanding the underlying molecular mechanisms of these diseases leads us to develop more accurate and effective treatments to reduce or mitigate their prevalence in the population. Given the global relevance of NCDs and ongoing research progress, this article reviews the current understanding about NCDs and their related risk factors, with a focus on obesity, diabetes, MAFLD, and CVDs, summarizing the knowledge about their pathophysiology and highlighting the currently available and emerging therapeutic strategies, especially pharmacological interventions. All of these diseases play an important role in the contamination by the SARS-CoV-2 virus, as well as in the progression and severity of the symptoms of the coronavirus disease 2019 (COVID-19). Therefore, we briefly explore the relationship between NCDs and COVID-19.
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Affiliation(s)
- João V. S. Guerra
- Brazilian Center for Research in Energy and Materials (CNPEM), Brazilian Biosciences National Laboratory (LNBio), Polo II de Alta Tecnologia—R. Giuseppe Máximo Scolfaro, Campinas 13083-100, Brazil; (J.V.S.G.); (M.M.G.D.); (M.F.T.)
- Graduate Program in Pharmaceutical Sciences, Faculty Pharmaceutical Sciences, University of Campinas, Campinas 13083-970, Brazil
| | - Marieli M. G. Dias
- Brazilian Center for Research in Energy and Materials (CNPEM), Brazilian Biosciences National Laboratory (LNBio), Polo II de Alta Tecnologia—R. Giuseppe Máximo Scolfaro, Campinas 13083-100, Brazil; (J.V.S.G.); (M.M.G.D.); (M.F.T.)
- Graduate Program in Functional and Molecular Biology, Institute of Biology, State University of Campinas (Unicamp), Campinas 13083-970, Brazil;
| | - Anna J. V. C. Brilhante
- Graduate Program in Functional and Molecular Biology, Institute of Biology, State University of Campinas (Unicamp), Campinas 13083-970, Brazil;
- Brazilian Center for Research in Energy and Materials (CNPEM), Brazilian Biorenewables National Laboratory (LNBR), Polo II de Alta Tecnologia—R. Giuseppe Máximo Scolfaro, Campinas 13083-100, Brazil
| | - Maiara F. Terra
- Brazilian Center for Research in Energy and Materials (CNPEM), Brazilian Biosciences National Laboratory (LNBio), Polo II de Alta Tecnologia—R. Giuseppe Máximo Scolfaro, Campinas 13083-100, Brazil; (J.V.S.G.); (M.M.G.D.); (M.F.T.)
- Graduate Program in Functional and Molecular Biology, Institute of Biology, State University of Campinas (Unicamp), Campinas 13083-970, Brazil;
| | - Marta García-Arévalo
- Brazilian Center for Research in Energy and Materials (CNPEM), Brazilian Biosciences National Laboratory (LNBio), Polo II de Alta Tecnologia—R. Giuseppe Máximo Scolfaro, Campinas 13083-100, Brazil; (J.V.S.G.); (M.M.G.D.); (M.F.T.)
- Correspondence: or (M.G.-A.); (A.C.M.F.)
| | - Ana Carolina M. Figueira
- Brazilian Center for Research in Energy and Materials (CNPEM), Brazilian Biosciences National Laboratory (LNBio), Polo II de Alta Tecnologia—R. Giuseppe Máximo Scolfaro, Campinas 13083-100, Brazil; (J.V.S.G.); (M.M.G.D.); (M.F.T.)
- Correspondence: or (M.G.-A.); (A.C.M.F.)
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Nana Nana AR, Tsobgny Tsague NF, Lontchi-Yimagou E, Bengondo Messanga C, Tankeu A, Katte JC, Balti Vounsia E, Dehayem M, Sobngwi E. Effects of non-surgical treatment of chronic periodontitis on insulin resistance and glucose tolerance in subjects without diabetes (PARODIA 2 study). J Investig Med 2021; 69:1377-1381. [PMID: 34261767 PMCID: PMC8485124 DOI: 10.1136/jim-2021-001831] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/15/2021] [Indexed: 11/03/2022]
Abstract
This study aimed to assess the effects of non-surgical periodontal treatment (NSPT) of chronic periodontitis on insulin sensitivity, glucose tolerance, and serum C reactive protein (CRP) level in individuals without diabetes. Twenty individuals without diabetes with chronic periodontitis underwent NSPT, which consisted of complete scaling, polishing, root planing, and irrigation of the periodontal pockets with a 10% povidone-iodine solution. Periodontal indices (plaque index, gingival bleeding index, pocket depth, and clinical attachment loss), insulin sensitivity using the Short Insulin Tolerance Test index (KITT), glucose tolerance derived from oral glucose tolerance test, and serum CRP level were measured before and 3 months after the intervention. This study was carried out at the National Obesity Center of Yaoundé Central Hospital, Cameroon. After 3 months, we observed significant improvement in periodontal parameters (all p<0.001) and insulin sensitivity (3.72 (2.99-4.17) %/min before treatment vs 4.04 (3.67-4.78) %/min after treatment, p=0.001) and significant decrease in serum CRP level (2.35 (1.46-4.18) mg/L before vs 1.53 (1.03-2.12) mg/L after, p=0.033). There was a trend toward improvement in glucose tolerance, although not statistically significant after the intervention. This study suggests that NSPT of chronic periodontitis in individuals without diabetes is associated with increased insulin sensitivity and decreased serum CRP levels.Trial registration number NCT02830113.
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Affiliation(s)
- Arnel Redon Nana Nana
- Department of Periodontology, Oral and Maxillo-Facial Surgery, University of Yaounde I Faculty of Medicine and Biomedical Sciences, Yaounde, Cameroon
| | - Nadia-Flore Tsobgny Tsague
- Department of Periodontology, Oral and Maxillo-Facial Surgery, University of Yaounde I Faculty of Medicine and Biomedical Sciences, Yaounde, Cameroon
| | - Eric Lontchi-Yimagou
- Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA.,Laboratory of Molecular Medicine and Metabolism, Biotechnology Center, Université de Yaoundé I, Yaounde, Cameroon
| | - Charles Bengondo Messanga
- Department of Periodontology, Oral and Maxillo-Facial Surgery, University of Yaounde I Faculty of Medicine and Biomedical Sciences, Yaounde, Cameroon
| | - Aurel Tankeu
- Department of Internal Medicine and Specialties, University of Yaounde I Faculty of Medicine and Biomedical Sciences, Yaounde, Cameroon
| | - Jean-Claude Katte
- Department of Public Health, Faculty of Medicine and Biomedical Sciences, University of Yaounde, Yaounde, Cameroon
| | - Eric Balti Vounsia
- Department of Internal Medicine and Specialties, University of Yaounde I Faculty of Medicine and Biomedical Sciences, Yaounde, Cameroon
| | - Mesmin Dehayem
- Department of Internal Medicine and Specialties, University of Yaounde I Faculty of Medicine and Biomedical Sciences, Yaounde, Cameroon
| | - Eugene Sobngwi
- Department of Internal Medicine and Specialties, University of Yaounde I Faculty of Medicine and Biomedical Sciences, Yaounde, Cameroon .,National Obesity Center, Yaoundé Central Hospital, Yaoundé, Cameroon
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Metabolic Syndrome: the Influence of Adipokines on the L-Arginine-NO Synthase-Nitric Oxide Signaling Pathway. ACTA BIOMEDICA SCIENTIFICA 2021. [DOI: 10.29413/abs.2021-6.2.3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Metabolic syndrome includes the following symptoms: obesity, hyperlipidemia, hypertension, insulin resistance, and cardiovascular disease. The purpose of this review is to elucidate the role of adipokines in the regulation of the L-arginine-NO-synthas-NO signaling pathway in the pathogenesis of metabolic syndrome. The main questions raised in the review are: how adipokine secretion changes, how the level of their receptors is regulated, and which signaling pathways are involved in the transmission of adipokine signals when coupled to the L-arginine-NO-synthase-NO signaling cascade. Adipokines are peptide hormones that transmit a signal from adipose tissue to targets in the brain, blood vessels, liver, pancreas, muscles, and other tissues. Some adipokines have anti-inflammatory and insulin-sensitive effects: adiponectin, omentin, adipolin, chemerin, progranulin. Others have the negative inflammatory effect in the development ofmetabolic syndrome: visfatin, vaspin, apelin. Adipokines primarily regulate the expression and activity of endothelial NO-synthase. They either activate an enzyme involving 5-AMP protein kinase or Akt kinase, increasing its activity and synthesis of NO in the tissues of healthy patients: adiponectin, adipolin, omentin, or inhibit the activity of eNOS, which leads to a decrease in NO-synthase and suppression of mRNA bioavailability: vaspin, visfatin, apelin in metabolic syndrome, and a decrease in its activity leads to dissociation and endothelial dysfunction. It should be noted that the bioavailability of NO formed by NO-synthase is affected at many levels, including: the expression ofNO-synthase mRNA and its protein; the concentration of L-arginine; the level of cofactors of the reaction; and to detect the maximum activity of endothelial NO-synthase, dimerization of the enzyme is required, posttranslational modifications are important, in particular, phosphorylation of endothelial NO-synthase by serine 1177 with the participation of 5-AMP protein kinase, Akt kinase and other kinases. It should be noted that the participation of adiponectin, omentin, and kemerin in the regulation of the L-arginine-NO-synthase-NO cascade in metabolic syndrom opens up certain opportunities for the development of new approaches for the correction of disorders observed in this disease. The review analyzes the results of research searching in PubMed databases, starting from 2001 and up to 2020 using keywords and adipokine names, more than half of the references of the last 5 years.
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Kalejahi P, Kheirouri S, Noorazar SG, Sanayei M. The relationship between brain-derived neurotrophic factor and metabolic syndrome in patients with chronic schizophrenia: A systematic review. Neuropeptides 2021; 87:102135. [PMID: 33812160 DOI: 10.1016/j.npep.2021.102135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Revised: 02/18/2021] [Accepted: 02/28/2021] [Indexed: 10/22/2022]
Abstract
BACKGROUND & AIMS Schizophrenia is a serious long-term disorder in which the metabolic complications and abnormalities of the brain-derived neurotrophic factor (BDNF) can be found. In this study, we conducted a systematic review of the relationship between BDNF, metabolic syndrome (MetS) and its components in schizophrenic patients. METHODS Data were collected mainly from PubMed, Google Scholar, Scopus, and ProQuest databases. The keywords related to the BDNF, MetS, schizophrenia were searched. Two reviewers independently screened 1061 abstracts. And eventually, a total of 7 studies (6 observational and 1 interventional) was included in the systematic reviews. RESULTS Four of the 7 study ascertained statistically significant inverse relationship between serum BDNF levels and MetS in schizophrenic patients. While in the other two studies, there was no inverse relationship. In the last selected study, the researchers found a weak association between the Val66Met polymorphism in BDNF Gene and clozapine-induced MetS. CONCLUSION Although this relationship could not be determined but BDNF levels appear to be reduced in schizophrenic patients with MetS and factors such as sex and antipsychotic class differentiation, sampling and methodology and episodes of illness could play a role in the results and outcomes.
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Affiliation(s)
- Parinaz Kalejahi
- Department of Community Nutrition, Faculty of Nutrition and Food sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sorayya Kheirouri
- Department of Community Nutrition, Faculty of Nutrition and Food sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Seyyed Gholamreza Noorazar
- Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mahzad Sanayei
- Department of Community Nutrition, Faculty of Nutrition and Food sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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Jing G, Wang H, Nan F, Liu Y, Zhang M. Naofucong Ameliorates High Glucose Induced Hippocampal Neuron Injury Through Suppressing P2X7/NLRP1/Caspase-1 Pathway. Front Pharmacol 2021; 12:647116. [PMID: 34093185 PMCID: PMC8173084 DOI: 10.3389/fphar.2021.647116] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 04/28/2021] [Indexed: 12/26/2022] Open
Abstract
P2X7/NLRP1/caspase-1 mediated neuronal injury plays an important role in diabetic cognitive impairment and eventually inflammatory cascade reaction. Chinese herbal compound Naofucong has been mainly used to treat cognitive disorders in Traditional Chinese Medicine The present study aimed to investigate whether its neuroprotective effects might be related to the inhibition of P2X7R/NLRP1/caspase-1 mediated neuronal injury or not. In this study, high glucose-induced HT22 hippocampal neurons were used to determine Naofucong-containing serum neuronal protective effects. Lentiviruses knock out of TXNIP and P2X7R was used to determine that protective effects of Naofucong was related to inflammatory response and P2X7/NLRP1/caspase-1 mediated neuronal injury. NAC was also used to inhibit oxidative stress, so as to determine that oxidative stress is an important starting factor for neuronal injury of HT22 cells cultured with high glucose. Naofucong decreased apoptosis, IL-1β and IL-18 levels in high glucose-induced HT22 hippocampal neuron cells. Naofucong suppressed NLRP1/caspase-1 mediated neuronal injury, and P2X7 was involved in process. HT22 cells cultured in high glucose had an internal environment with elevated oxidative stress, which could promote neuronal injury. The current study demonstrated that Naofucong could significantly improve high glucose-induced HT22 hippocampal neuron injury, which might be related to suppress P2X7R/NLRP1/caspase-1 pathway, which provides novel evidence to support the future clinical use of Naofucong.
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Affiliation(s)
- Guangchan Jing
- Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Huanyuan Wang
- Acupuncture and Tuina Department, Qilu Hospital of Shandong University, Jinan, China
| | - Fengwei Nan
- Department of Endocrinology, Kaifeng Hospital of Traditional Chinese Medicine, Kaifeng, China
| | - Yuqin Liu
- Department of Cell Resource Center, Institute of Basic Medical Science, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Mengren Zhang
- Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Ying W, Gao H, Dos Reis FCG, Bandyopadhyay G, Ofrecio JM, Luo Z, Ji Y, Jin Z, Ly C, Olefsky JM. MiR-690, an exosomal-derived miRNA from M2-polarized macrophages, improves insulin sensitivity in obese mice. Cell Metab 2021; 33:781-790.e5. [PMID: 33450179 PMCID: PMC8035248 DOI: 10.1016/j.cmet.2020.12.019] [Citation(s) in RCA: 187] [Impact Index Per Article: 46.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 10/20/2020] [Accepted: 12/28/2020] [Indexed: 02/07/2023]
Abstract
Insulin resistance is a major pathophysiologic defect in type 2 diabetes and obesity, while anti-inflammatory M2-like macrophages are important in maintaining normal metabolic homeostasis. Here, we show that M2 polarized bone marrow-derived macrophages (BMDMs) secrete miRNA-containing exosomes (Exos), which improve glucose tolerance and insulin sensitivity when given to obese mice. Depletion of their miRNA cargo blocks the ability of M2 BMDM Exos to enhance insulin sensitivity. We found that miR-690 is highly expressed in M2 BMDM Exos and functions as an insulin sensitizer both in vivo and in vitro. Expressing an miR-690 mimic in miRNA-depleted BMDMs generates Exos that recapitulate the effects of M2 BMDM Exos on metabolic phenotypes. Nadk is a bona fide target mRNA of miR-690, and Nadk plays a role in modulating macrophage inflammation and insulin signaling. Taken together, these data suggest miR-690 could be a new therapeutic insulin-sensitizing agent for metabolic disease.
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Affiliation(s)
- Wei Ying
- Division of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, San Diego, CA, USA.
| | - Hong Gao
- Division of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, San Diego, CA, USA
| | | | - Gautam Bandyopadhyay
- Division of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, San Diego, CA, USA
| | - Jachelle M Ofrecio
- Division of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, San Diego, CA, USA
| | - Zhenlong Luo
- Division of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, San Diego, CA, USA
| | - Yudong Ji
- Division of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, San Diego, CA, USA
| | - Zhongmou Jin
- Division of Biological Sciences, University of California, San Diego, San Diego, CA, USA
| | - Crystal Ly
- Division of Biological Sciences, University of California, San Diego, San Diego, CA, USA
| | - Jerrold M Olefsky
- Division of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, San Diego, CA, USA.
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Wittwer J, Bradley D. Clusterin and Its Role in Insulin Resistance and the Cardiometabolic Syndrome. Front Immunol 2021; 12:612496. [PMID: 33717095 PMCID: PMC7946829 DOI: 10.3389/fimmu.2021.612496] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 02/04/2021] [Indexed: 12/12/2022] Open
Abstract
The cardiometabolic syndrome involves a clustering of metabolic and cardiovascular factors which increase the risk of patients developing both Type 2 Diabetes Mellitus and cardio/cerebrovascular disease. Although the mechanistic underpinnings of this link remain uncertain, key factors include insulin resistance, excess visceral adiposity, atherogenic dyslipidemia, and endothelial dysfunction. Of these, a state of resistance to insulin action in overweight/obese patients appears to be central to the pathophysiologic process. Given the increasing prevalence of obesity-related Type 2 Diabetes, coupled with the fact that cardiovascular disease is the number one cause of mortality in this patient population, a more thorough understanding of the cardiometabolic syndrome and potential options to mitigate its risk is imperative. Inherent in the pathogenesis of insulin resistance is an underlying state of chronic inflammation, at least partly in response to excess adiposity. Within obese adipose tissue, an immunomodulatory shift occurs, involving a preponderance of pro-inflammatory immune cells and cytokines/adipokines, along with antigen presentation by adipocytes. Therefore, various adipokines differentially expressed by obese adipocytes may have a significant effect on cardiometabolism. Clusterin is a molecular chaperone that is widely produced by many tissues throughout the body, but is also preferentially overexpressed by obese compared lean adipocytes and relates strongly to multiple components of the cardiometabolic syndrome. Herein, we summarize the known and potential roles of circulating and adipocyte-specific clusterin in cardiometabolism and discuss potential further investigations to determine if clusterin is a viable target to attenuate both metabolic and cardiovascular disease.
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Affiliation(s)
- Jennifer Wittwer
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Diabetes and Metabolism Research Center, The Ohio State University, Columbus, OH, United States
| | - David Bradley
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Diabetes and Metabolism Research Center, The Ohio State University, Columbus, OH, United States
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Rice Bran Oil Attenuates Chronic Inflammation by Inducing M2 Macrophage Switching in High-Fat Diet-Fed Obese Mice. Foods 2021; 10:foods10020359. [PMID: 33562395 PMCID: PMC7914799 DOI: 10.3390/foods10020359] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 02/03/2021] [Accepted: 02/04/2021] [Indexed: 01/05/2023] Open
Abstract
Macrophages are involved in all inflammatory processes from killing pathogens to repairing damaged tissue. In the obese state, macrophages infiltrate into enlarged adipose tissue and polarize into pro-inflammatory M1 macrophages, resulting in chronic low-grade inflammation due to the secretion of inflammatory mediators. Rice bran oil (RBO) is an edible oil containing tocopherols, tocotrienols, and γ-oryzanol. Previous research in normal diet-fed mice suggested that RBO mitigates inflammatory responses by modulating mitochondrial respiration of macrophages. Therefore, we investigated if RBO had an anti-inflammatory effect in diet-induced obese mice by assessing the expression of inflammatory markers in epididymal white adipose tissue (eWAT) and polarization of bone marrow-derived macrophages (BMDMs). Rice bran oil exerted a local anti-inflammatory effect in white adipose tissue by suppressing the production of inflammatory mediators and upregulating transcription of anti-inflammatory genes. Rice bran oil also promoted anti-inflammatory M2 macrophage polarization in BMDMs thereby affecting systemic inflammation. Overall, our in vivo and ex vivo results highlight the potential of RBO as a dietary mediator that can ameliorate obesity-induced chronic low-grade inflammation by mediating the expression of inflammation-related factors and macrophage polarization.
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Alves da Silva R, Bersch-Ferreira ÂC, Gehringer MO, Ross-Fernandes MB, Kovacs do Amaral C, Lin Wang HT, Lima PH, de Lima PA, França JÍ, Weber B, Magnoni CD, Rogero MM. Effect of qualitative and quantitative nutritional plan on gene expression in obese patients in secondary prevention for cardiovascular disease. Clin Nutr ESPEN 2021; 41:351-359. [PMID: 33487289 DOI: 10.1016/j.clnesp.2020.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 10/29/2020] [Accepted: 11/01/2020] [Indexed: 11/25/2022]
Abstract
BACKGROUND & AIMS Diet is a modifiable risk factor, which may influence the gene expression and the concentration of inflammatory biomarkers related to obesity and atherosclerosis. In this substudy from Brazilian Cardioprotective Nutritional (BALANCE) Program, we hypothesized that a nutritional intervention based on the usual Brazilian diet modulates the expression of genes involved with atherosclerosis and inflammatory biomarkers in male patients, in the secondary prevention for cardiovascular disease. METHODS Six male patients, aged 45 years or older, obese, were selected to follow a qualitative-quantitative food plan for 6 months. Glycemia, insulinemia, lipid profile, plasma concentration of inflammatory biomarkers (interleukin (IL) -1β), IL-6, IL-8, IL-10, IL-12, tumor necrosis factor alpha, C-reactive protein and adiponectin, and expression of 84 atherosclerosis-related genes in total peripheral blood cells, were measured. RESULTS After nutritional intervention, the participants reduced weight (p < 0.04), waist circumference (p < 0.04), Homeostasis Model Assessment index for insulin resistance (p = 0.046) and overall leukocyte count (p = 0.046) and neutrophils (p = 0.028). There was no significant modification in the plasma concentration of the inflammatory biomarkers, however, there was a significant increase in the expression of Apo A1 (p = 0.011), ELN (p = 0.017) and IL4 (p = 0.037) genes. CONCLUSIONS The BALANCE Program, the qualitative-quantitative food plan composed of Brazilian usual foods, did not reduce the concentration of inflammatory biomarkers, but increased in total peripheral blood cells the expression of genes involved in reducing the risk of cardiometabolic in obese patients, in secondary prevention for cardiovascular disease. The clinical trial is registered at https://clinicaltrials.gov/ and the unique identifier is NCT01620398.
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Affiliation(s)
- Renata Alves da Silva
- Department of Clinical Nutrition, Instituto Dante Pazzanese de Cardiologia, 04012-090, São Paulo, SP, Brazil.
| | | | - Marcella Omena Gehringer
- Nutritional Genomics and Inflammation Laboratory, Department of Nutrition, School of Public Health, University of São Paulo, 01246-904, São Paulo, Brazil.
| | - Maria Beatriz Ross-Fernandes
- Nutritional Genomics and Inflammation Laboratory, Department of Nutrition, School of Public Health, University of São Paulo, 01246-904, São Paulo, Brazil.
| | - Cristiane Kovacs do Amaral
- Department of Clinical Nutrition, Instituto Dante Pazzanese de Cardiologia, 04012-090, São Paulo, SP, Brazil.
| | - Hui-Tzu Lin Wang
- Department of Clinical Nutrition, Instituto Dante Pazzanese de Cardiologia, 04012-090, São Paulo, SP, Brazil.
| | - Paula Helena Lima
- Department of Clinical Nutrition, Instituto Dante Pazzanese de Cardiologia, 04012-090, São Paulo, SP, Brazil.
| | - Patrícia Azevedo de Lima
- Nutritional Genomics and Inflammation Laboratory, Department of Nutrition, School of Public Health, University of São Paulo, 01246-904, São Paulo, Brazil.
| | - João Ítalo França
- Department of Clinical Nutrition, Instituto Dante Pazzanese de Cardiologia, 04012-090, São Paulo, SP, Brazil.
| | - Bernardete Weber
- Research Institute - Hospital do Coração, 04005-000, São Paulo, SP, Brazil.
| | - Carlos Daniel Magnoni
- Department of Clinical Nutrition, Instituto Dante Pazzanese de Cardiologia, 04012-090, São Paulo, SP, Brazil.
| | - Marcelo Macedo Rogero
- Nutritional Genomics and Inflammation Laboratory, Department of Nutrition, School of Public Health, University of São Paulo, 01246-904, São Paulo, Brazil.
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Medhat D, El-Bana MA, El-Daly SM, Ashour MN, Elias TR, Mohamed RA, Yassen NN, Abdel-Monem MA, Hussein J. Influence of irisin on diet-induced metabolic syndrome in experimental rat model. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2021; 18:347-354. [PMID: 34187125 DOI: 10.1515/jcim-2020-0030] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Accepted: 06/29/2020] [Indexed: 11/15/2022]
Abstract
OBJECTIVE To evaluate the influence of irisin on the experimental paradigm of non-alcoholic fatty liver (NAFL) as a part of MetS cluster. METHODS Forty male albino rats were divided into four groups; normal control, standard diet + irisin, high carbohydrate and fat diet (HCHF), and HCHF + irisin. After the experimental period, levels of fasting blood sugar (FBS), insulin, lipid profile, kidney functions, salusin-alpha (Sal-α), adropin, and retinol-binding protein-4 (RBP-4) were evaluated. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α) expression in skeletal muscle was evaluated by quantitative real-time PCR. Aorta, liver, pancreas, and skeletal muscle tissue samples were prepared for histopathological examination. RESULTS Rats administrated HCHF showed elevated levels of FBS, lipid profile, kidney functions, RBP-4, and downregulation of PGC-1α expression along with a decline in levels of insulin, Sal-α, and adropin while administration of irisin significantly attenuated these levels. CONCLUSIONS Irisin as based therapy could emerge as a new line of treatment against MetS and its related diseases.
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Affiliation(s)
- Dalia Medhat
- Medical Biochemistry Department, National Research Centre, Doki, Giza, Egypt
| | - Mona A El-Bana
- Medical Biochemistry Department, National Research Centre, Doki, Giza, Egypt
| | - Sherien M El-Daly
- Medical Biochemistry Department, National Research Centre, Doki, Giza, Egypt
| | - Magdi N Ashour
- Medical Biochemistry Department, National Research Centre, Doki, Giza, Egypt
| | - Tahany R Elias
- Medical Biochemistry Department, National Research Centre, Doki, Giza, Egypt
| | - Rehab A Mohamed
- Medical Biochemistry Department, National Research Centre, Doki, Giza, Egypt
| | - Noha N Yassen
- Pathology Department, Medical Division, National Research Centre, Doki, Giza, Egypt
| | | | - Jihan Hussein
- Medical Biochemistry Department, National Research Centre, Doki, Giza, Egypt
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Wang Y, Tang B, Long L, Luo P, Xiang W, Li X, Wang H, Jiang Q, Tan X, Luo S, Li H, Wang Z, Chen Z, Leng Y, Jiang Z, Wang Y, Ma L, Wang R, Zeng C, Liu Z, Wang Y, Miao H, Shi C. Improvement of obesity-associated disorders by a small-molecule drug targeting mitochondria of adipose tissue macrophages. Nat Commun 2021; 12:102. [PMID: 33397994 PMCID: PMC7782823 DOI: 10.1038/s41467-020-20315-9] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2019] [Accepted: 11/25/2020] [Indexed: 12/20/2022] Open
Abstract
Pro-inflammatory activation of adipose tissue macrophages (ATMs) is causally linked to obesity and obesity-associated disorders. A number of studies have demonstrated the crucial role of mitochondrial metabolism in macrophage activation. However, there is a lack of pharmaceutical agents to target the mitochondrial metabolism of ATMs for the treatment of obesity-related diseases. Here, we characterize a near-infrared fluorophore (IR-61) that preferentially accumulates in the mitochondria of ATMs and has a therapeutic effect on diet-induced obesity as well as obesity-associated insulin resistance and fatty liver. IR-61 inhibits the classical activation of ATMs by increasing mitochondrial complex levels and oxidative phosphorylation via the ROS/Akt/Acly pathway. Taken together, our findings indicate that specific enhancement of ATMs oxidative phosphorylation improves chronic inflammation and obesity-related disorders. IR-61 might be an anti-inflammatory agent useful for the treatment of obesity-related diseases by targeting the mitochondria of ATMs. Adipose tissue macrophages are central to controlling inflammation in the context of obesity. Here the authors present a new infrared dye (IR-61) that accumulates in the mitochondria of these cells resulting in anti-inflammatory effects that counter obesity-associated pathology in mice.
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Affiliation(s)
- Yawei Wang
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China
| | - Binlin Tang
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China.,Oncology Department, The General Hospital of Western Theater Command, Chengdu, Sichuan, 610083, China
| | - Lei Long
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China
| | - Peng Luo
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China
| | - Wei Xiang
- Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing, 400038, China
| | - Xueru Li
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China
| | - Huilan Wang
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China.,Department of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Qingzhi Jiang
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China.,Department of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Xu Tan
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China
| | - Shenglin Luo
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China
| | - Huijuan Li
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China
| | - Ziwen Wang
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China
| | - Zelin Chen
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China
| | - Yu Leng
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China
| | - Zhongyong Jiang
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China
| | - Yang Wang
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China
| | - Le Ma
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China
| | - Rui Wang
- Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, 400042, China
| | - Chunyu Zeng
- Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, 400042, China
| | - Zujuan Liu
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China
| | - Yu Wang
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China.
| | - Hongming Miao
- Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing, 400038, China.
| | - Chunmeng Shi
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China.
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Janczura M, Rosa R, Dropinski J, Gielicz A, Stanisz A, Kotula-Horowitz K, Domagala T. The Associations of Perceived and Oxidative Stress with Hypertension in a Cohort of Police Officers. Diabetes Metab Syndr Obes 2021; 14:1783-1797. [PMID: 33953580 PMCID: PMC8090790 DOI: 10.2147/dmso.s298596] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 03/13/2021] [Indexed: 12/26/2022] Open
Abstract
PURPOSE Associations between perceived stress and oxidative stress marker and metabolic syndrome (MetS) components were investigated in a cohort of police officers. METHODS Cross-sectional data from a cohort of non-diabetic subjects (n=233; 19F), median [interquartile range] age 50 [37-44] years, were analysed. MetS was construed in line with International Diabetes Federation (IDF) criteria and perceived stress with Cohen's 10-item Perceived Stress Scale. Plasma oxidative stress marker (free 8-iso-prostaglandin F2α; 8-iso-PGF2α), presence of coronary plaque, carotid artery intima-media thickness (cIMT), and physical activity level were also determined. RESULTS Obesity was established in 100 (42.92%), hypertension in 111 (47.64), whereas MetS was identified in 104 (44.63%) of the study subjects. A significant difference (p=0.003) in plasma 8-iso-PGF2α level, depending on the MetS components status, was noted. The associations of perceived stress with plasma 8-iso-PGF2α level and the select study variables were gender-specific. In multivariate analysis (adjusted for age and current smoking), positive associations of plasma 8-iso-PGF2α levels with PSS score (B=0.108, 95% CI [0.008, 0.209], p=0.03) and systolic blood pressure (B=0.029, 95% CI [0.003, 0.057], p=0.02) in men only were established. Both the perceived stress (OR 1.101, 95% CI [1.001-1.202], p=0.03) and plasma 8-iso-PGF2α levels (OR 1.223, 95% CI [1.046-1.432], p=0.01) impacted the prevalence of hypertension. Out of the MetS components, the effect of waist circumference (OR=1.138, 95% CI [1.064-1.218], p=0.0001) and glucose (B=2.696, 95% CI [1.081-6.725], p=0.03) were also encountered. No such associations were noted in women, though, neither in univariate nor in multivariate analyses. The prevalence of coronary plaque (0.001), obesity (p<0.001), hypertension (p<0.001) and median cIMT value (p=0.005), as well as leisure-time (p=0.04) and total walking physical activity (p=0.03), differed significantly between the subgroups stratified by MetS components status. CONCLUSION Both the perceived and oxidative stress were found instrumental in promoting hypertension in a cohort of police officers under study, whereas all study outcomes were conclusively gender-related.
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Affiliation(s)
- Miroslaw Janczura
- Faculty of Health Sciences, Jagiellonian University School of Medicine, Krakow, Poland
| | - Rafal Rosa
- Health Care Centre of the Ministry of the Interior and Administration, Department of Anesthesiology and Intensive Care, Krakow, Poland
| | - Jerzy Dropinski
- Department of Internal Medicine, Jagiellonian University School of Medicine, Krakow, Poland
| | - Anna Gielicz
- Department of Internal Medicine, Jagiellonian University School of Medicine, Krakow, Poland
| | - Andrzej Stanisz
- Department of Bioinformatics and Telemedicine, Jagiellonian University School of Medicine, Krakow, Poland
| | - Katarzyna Kotula-Horowitz
- Health Care Centre of the Ministry of the Interior and Administration, Department of Internal Medicine, Krakow, Poland
| | - Teresa Domagala
- Department of Medical Biochemistry, Jagiellonian University School of Medicine, Krakow, Poland
- Correspondence: Teresa Domagala Department of Medical Biochemistry, Jagiellonian University School of Medicine, Krowoderska 68/11, Krakow, 31-158, PolandTel +48 12 422 74 00Fax +48 12 422 32 72 Email
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