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1
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Yang S, Zhang S, Deng J, Xie J, Zhang J, Jia E. Association of systemic immune-inflammation index with body mass index, waist circumference and prevalence of obesity in US adults. Sci Rep 2024; 14:22086. [PMID: 39333666 PMCID: PMC11436774 DOI: 10.1038/s41598-024-73659-3] [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: 01/29/2024] [Accepted: 09/19/2024] [Indexed: 09/29/2024] Open
Abstract
This study aims to investigate the potential relationships between the systemic immune-inflammation index (SII) and body mass index (BMI), waist circumference, and the prevalence of obesity. A cross-sectional analysis was conducted on 7,645 individuals aged 20 and above from the NHANES 2017-2020. Multivariate linear regression analyses were conducted to evaluate the association of the logarithmically transformed SII (lgSII) with BMI and waist circumference. Additionally, multivariable logistic regression was utilized to explore the relationship between lgSII and the prevalence of obesity. Fitted smoothing curves and threshold-effect analysis were applied to elucidate nonlinear relationships. In the fully adjusted model, a positive relationship was observed between lgSII and BMI, waist circumference, and obesity prevalence (β = 3.13, 95% CI 2.10-4.16; β = 7.81, 95% CI 5.50-10.13; OR = 1.44, 95% CI 1.12-1.86). The variables of gender, age, race, education, marital status, poverty income ratio (PIR), energy intake, sleep disorder, smoking status, and alcohol use did not significantly modify the positive association between lgSII and obesity. However, physical activity appeared to influence the positive correlation between lgSII and obesity. Using a two-segment linear regression model, an inverted U-shaped relationship was observed between lgSII and both BMI and waist circumference. Furthermore, lgSII demonstrated a linear positive correlation with obesity prevalence. When stratified by physical activity, lgSII showed a non-significant negative correlation with obesity in the physically active group. Our findings underscore a robust association between the logarithmically transformed SII and BMI, waist circumference, and the prevalence of obesity.
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Affiliation(s)
- Shuo Yang
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, People's Republic of China
| | - Shan Zhang
- Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Shenzhen, Guangdong, People's Republic of China
| | - Jinrong Deng
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, People's Republic of China
| | - Jingjing Xie
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, People's Republic of China
- Department of Rheumatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, People's Republic of China
| | - Jianyong Zhang
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, People's Republic of China.
- Department of Rheumatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, People's Republic of China.
| | - Ertao Jia
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, People's Republic of China.
- Department of Rheumatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, People's Republic of China.
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2
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Marin AG, Filipescu A, Petca A. The Role of Obesity in the Etiology and Carcinogenesis of Endometrial Cancer. Cureus 2024; 16:e59219. [PMID: 38807790 PMCID: PMC11132319 DOI: 10.7759/cureus.59219] [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] [Accepted: 04/28/2024] [Indexed: 05/30/2024] Open
Abstract
Endometrial cancer, the most common gynecological malignancy, presents a complex public health challenge. While its incidence rises alongside the obesity epidemic, a well-established risk factor for endometrial cancer development, the impact of obesity on survival after diagnosis remains unclear. This review aims to explore the complex relationship between obesity and endometrial cancer's development and survival rates, examining evidence from both epidemiological and clinical studies. It also aims to explore the proposed biological mechanisms by which excess adipose tissue promotes carcinogenesis and contributes to endometrial cancer progression and its negative effects on treatment outcomes. Furthermore, we analyzed the impact of body mass index, inflammation, hormonal imbalances, and their potential effects on endometrial cancer survival rates.
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Affiliation(s)
| | - Alexandru Filipescu
- Obstetrics and Gynaecology, Elias Emergency University Hospital, Bucharest, ROU
| | - Aida Petca
- Obstetrics and Gynaecology, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
- Obstetrics and Gynaecology, Elias Emergency University Hospital, Bucharest, ROU
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3
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Jha D, Prajapati SK, Deb PK, Jaiswal M, Mazumder PM. Madhuca longifolia-hydro-ethanolic-fraction reverses mitochondrial dysfunction and modulates selective GLUT expression in diabetic mice fed with high fat diet. Mol Biol Rep 2024; 51:209. [PMID: 38270737 DOI: 10.1007/s11033-023-08962-9] [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: 07/25/2023] [Accepted: 10/30/2023] [Indexed: 01/26/2024]
Abstract
BACKGROUND Metabolic disorder is characterized as chronic low-grade inflammation which elevates the systemic inflammatory markers. The proposed hypothesis behind this includes occurrence of hypoxia due to intake of high fat diet leading to oxidative stress and mitochondrial dysfunction. AIM In the present work our aim was to elucidate the possible mechanism of action of hydroethanolic fraction of M. longifolia leaves against the metabolic disorder. METHOD AND RESULTS In the present investigation, effect of Madhuca longifolia hydroethanolic fraction (MLHEF) on HFD induced obesity and diabetes through mitochondrial action and selective GLUT expression has been studied. In present work, it was observed that HFD (50% of diet) on chronic administration aggravates the metabolic problems by causing reduced imbalanced oxidative stress, ATP production, and altered selective GLUT protein expression. Long term HFD administration reduced (p < 0.001) the SOD, CAT level significantly along with elevated liver function marker AST and ALT. MLHEF administration diminishes this oxidative stress. HFD administration also causes decreased ATP/ADP ratio owing to suppressed mitochondrial function and elevating LDH level. This oxidative imbalance further leads to dysregulated GLUT expression in hepatocytes, skeletal muscles and white adipose tissue. HFD leads to significant (p < 0.001) upregulation in GLUT 1 and 3 expression while significant (p < 0.001) downregulation in GLUT 2 and 4 expressions in WAT, liver and skeletal muscles. Administration of MLHEF significantly (p < 0.001) reduced the LDH level and also reduces the mitochondrial dysfunction. CONCLUSION Imbalances in GLUT levels were significantly reversed in order to maintain GLUT expression in tissues on the administration of MLHEF.
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Affiliation(s)
- Dhruv Jha
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, 835215, India.
| | - Santosh Kumar Prajapati
- Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, 33613, USA
| | - Prashanta Kumar Deb
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, 835215, India
| | - Mohit Jaiswal
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, 835215, India
| | - Papiya Mitra Mazumder
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, 835215, India
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4
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Ruck L, Wiegand S, Kühnen P. Relevance and consequence of chronic inflammation for obesity development. Mol Cell Pediatr 2023; 10:16. [PMID: 37957462 PMCID: PMC10643747 DOI: 10.1186/s40348-023-00170-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 10/26/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND Increasing prevalence of morbid obesity accompanied by comorbidities like type 2 diabetes mellitus (T2DM) led to a demand for improving therapeutic strategies and pharmacological intervention options. Apart from genetics, inflammation processes have been hypothesized to be of importance for the development of obesity and related aspects like insulin resistance. MAIN TEXT Within this review, we provide an overview of the intricate interplay between chronic inflammation of the adipose tissue and the hypothalamus and the development of obesity. Further understanding of this relationship might improve the understanding of the underlying mechanism and may be of relevance for the establishment of new treatment strategies.
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Affiliation(s)
- Lisa Ruck
- Klinik Für Pädiatrische Endokrinologie und Diabetologie, Charité Universitätsmedizin, Berlin, Germany.
- Berlin Institute of Health at Charité-Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Junior Clinician Scientist Program, Charitéplatz 1, 10117, Berlin, Germany.
| | - Susanna Wiegand
- Abteilung Interdisziplinär, Sozial-Pädiatrisches Zentrum, Charité Universitätsmedizin, Berlin, Germany
| | - Peter Kühnen
- Klinik Für Pädiatrische Endokrinologie und Diabetologie, Charité Universitätsmedizin, Berlin, Germany
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5
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Carrera-Juliá S, Estrela JM, Zacarés M, Navarro MÁ, Vega-Bello MJ, de la Rubia Ortí JE, Moreno ML, Drehmer E. Effect of the Mediterranean diet supplemented with nicotinamide riboside and pterostilbene and/or coconut oil on anthropometric variables in amyotrophic lateral sclerosis. A pilot study. Front Nutr 2023; 10:1232184. [PMID: 37810917 PMCID: PMC10556480 DOI: 10.3389/fnut.2023.1232184] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 09/11/2023] [Indexed: 10/10/2023] Open
Abstract
Amyotrophic Lateral Sclerosis (ALS) is a chronic and progressive neurodegenerative disease that causes the death of motor neurons and alters patients' body composition. Supplementation with the antioxidants nicotinamide riboside (NR) and pterostilbene (PTER) can combat associated oxidative stress. Additionally, coconut oil is an alternative energy substrate that can address mitochondrial dysfunction. The aim of the present study is to assess the impact of a Mediterranean Diet supplemented with NR and PTER and/or with coconut oil on the anthropometric variables of patients with ALS. A prospective, mixed, randomized, analytical and experimental pilot study in humans was performed through a clinical trial (registered with ClinicalTrials.gov under number NCT03489200) with pre- and post-intervention assessments. The sample was made up of 40 subjects categorized into four study groups (Control, Antioxidants, Coconut oil, and Antioxidants + Coconut oil). Pre- and post-intervention anthropometric assessments were carried out to determine the following data: weight, percentage of fat and muscle mass, skinfolds, body perimeters, Body Mass Index (BMI), Waste-to-Hip Index (WHI) and Waist-Height Ratio (WHR). Compared to the Control group, GAx significantly increased muscle mass percentage and decreased fat mass percentage, triceps, iliac crest, and abdominal skinfolds. GCoco significantly increased muscle mass percentage and decreased fat mass percentage, subscapular skinfolds, and abdominal skinfolds. GAx + coco significantly increased muscle mass percentage and decreased abdominal skinfolds. Therefore, our results suggest that the Mediterranean Diet supplemented with NR and PTER and the Mediterranean Diet supplemented with coconut oil (ketogenic diet) are the two nutritional interventions that have reported the greatest benefits, at anthropometric level.
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Affiliation(s)
- Sandra Carrera-Juliá
- Department of Nutrition and Dietetics, Catholic University of Valencia San Vicente Mártir, Valencia, Spain
| | - José M. Estrela
- Department of Physiology, University of Valencia, Valencia, Spain
| | - Mario Zacarés
- Department of Basic and Transversal Sciences, Catholic University of Valencia San Vicente Mártir, Valencia, Spain
| | - Mari Ángeles Navarro
- Department of Basic and Transversal Sciences, Catholic University of Valencia San Vicente Mártir, Valencia, Spain
| | - María Jesús Vega-Bello
- Department of Human Anatomy and Physiology, Catholic University of Valencia San Vicente Mártir, Valencia, Spain
| | | | - Mari Luz Moreno
- Department of Human Anatomy and Physiology, Catholic University of Valencia San Vicente Mártir, Valencia, Spain
| | - Eraci Drehmer
- Department of Health and Functional Assessment, Catholic University of Valencia San Vicente Mártir, Valencia, Spain
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de Mello RN, de Gois BP, Kravchychyn ACP, Dâmaso AR, Horst MA, Lima GC, Corgosinho FC. Dietary inflammatory index and its relation to the pathophysiological aspects of obesity: a narrative review. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2023; 67:e000631. [PMID: 37364142 PMCID: PMC10661000 DOI: 10.20945/2359-3997000000631] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 01/20/2023] [Indexed: 06/28/2023]
Abstract
Obesity, a complex disease that involves energy imbalance and chronic low-grade inflammation, is implicated in the pathogenesis of several chronic non-communicable diseases. As dietary components modulate the human body's inflammatory status, the Dietary Inflammatory Index (DII®), a literature-derived dietary index, was developed in 2009 to characterize the inflammatory potential of a habitual diet. Abundant research has been conducted to investigate the associations between DII and obesity. In this narrative review, we examined the current state of the science regarding the relationships between DII and the inflammatory pathophysiological aspects related to obesity. DII is associated with inflammation in obesity. The most pro-inflammatory diet was directly related to higher levels of pro-inflammatory markers, which included C-reactive protein (CRP), interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α). Therefore, evidence suggests that the use of the DII may be useful for understanding the relationship between diet and the inflammatory process related to obesity.
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Affiliation(s)
- Roseli Neves de Mello
- Universidade Federal de Goiás, Faculdade de Nutrição, Programa de Pós-graduação em Nutrição e Saúde, Goiânia, GO, Brasil
| | - Bárbara Paixão de Gois
- Universidade Federal de Goiás, Faculdade de Nutrição, Programa de Pós-graduação em Nutrição e Saúde, Goiânia, GO, Brasil
| | | | - Ana Raimunda Dâmaso
- Universidade Federal de São Paulo, Escola Paulista de Medicina, Programa de Pós-graduação em Nutrição, São Paulo, SP, Brasil
| | - Maria Aderuza Horst
- Universidade Federal de Goiás, Faculdade de Nutrição, Programa de Pós-graduação em Nutrição e Saúde, Goiânia, GO, Brasil
| | - Glaucia Carielo Lima
- Universidade Federal de Goiás, Faculdade de Nutrição, Programa de Pós-graduação em Nutrição e Saúde, Goiânia, GO, Brasil
| | - Flávia Campos Corgosinho
- Universidade Federal de Goiás, Faculdade de Nutrição, Programa de Pós-graduação em Nutrição e Saúde, Goiânia, GO, Brasil
- Universidade Federal de Goiás, Programa de Pós-graduação e Ciências da Saúde, Goiânia, GO, Brasil,
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7
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Seroprevalence of varicella-zoster virus antibody and immunogenicity of live attenuated varicella vaccine in healthcare workers in Taiwan. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2023; 56:274-281. [PMID: 36243667 DOI: 10.1016/j.jmii.2022.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 08/24/2022] [Accepted: 09/23/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND Healthcare workers (HCWs) without evidence of immunity to varicella-zoster virus (VZV) are recommended to undergo varicella vaccination. Immunogenicity of live attenuated varicella vaccine has rarely been investigated among HCWs in Taiwan. METHODS Anti-VZV immunoglobulin G (IgG) titer was checked for all HCWs at Changhua Christian Hospital from 2011 to 2017. One-dose and two-dose (separated by 4-8 weeks) vaccines were administered to HCWs with equivocal and negative anti-varicella IgG results, respectively. Follow-up anti-VZV IgG was determined at least 4 weeks after completion of vaccination. Factors associated with seroconversion to varicella vaccination were analyzed. RESULTS Among 2406 included HCWs, the anti-VZV IgG serostatus was tested positive, equivocal and negative in 1924 (79.9%), 117 (4.9%) and 365 (15.2%), respectively. The seroprevalence had decreased from 88.0% (235/267) in 2011 to 72.2% (270/374) in 2017 (p for trend <0.05). A total of 67.8% (327/482) HCWs completed scheduled vaccination and serological follow-up. The seroconversion rates for HCWs with baseline equivocal and negative anti-VZV IgG results were 100% (80/80) and 79.4% (196/247) after one- and two-dose vaccination, respectively. In multivariate analysis, obesity (adjusted odds ratio, 0.308; 95% confidence interval [CI], 0.11-0.94, p = 0.039) was the only factor statistically significantly associated with seroconversion to vaccination. CONCLUSION Decreasing trends of seroprevalence of VZV were observed among HCWs from 2011 to 2017. HCWs who were obese were less likely to respond to varicella vaccination.
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Abstract
Metabolic syndrome (MS), a conglomeration of several conditions including obesity, type 2 diabetes mellitus (T2DM), insulin resistance, elevated blood pressure, and dyslipidemia is reaching epidemic proportions. Anemia is caused by iron deficiency or dysregulation of iron homeostasis, leading to tissue hypoxia. Coexistence of anemia and MS or its components has been reported in the literature. The term "rubrometabolic syndrome" acts as a unifying entity linking the importance of blood in health and anemia in MS; it justifies two principles - redness of blood and low-grade inflammation. Chronic low-grade inflammation in MS affects iron metabolism leading to anemia. Tissue hypoxia that results from the anemic condition seems to be a major causative factor for the exacerbation of several microvascular and macrovascular components of T2DM, which include diabetic neuropathy, nephropathy, retinopathy, and cardiovascular complications. In obesity, anemia leads to malabsorption of micronutrients and can complicate the management of the condition by bariatric surgery. Anemia interferes with the diagnosis and management of T2DM, obesity, dyslipidemia, or hypertension due to its effect on pathological tests as well as medications. Since anemia in MS is multifaceted, the management of anemia is challenging as overcorrection of anemia with erythropoietin-stimulating agents can cause detrimental effects. These limitations necessitate availability of an effective and safe therapy that can maintain and elevate the hemoglobin levels along with maintaining the physiological balance of other systems. This review discusses the physiological links between anemia and MS along with diagnosis and management strategies in patients with coexistence of anemia and MS.
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Affiliation(s)
| | - Ankia Coetzee
- Division of Endocrinology, Stellenbosch University & Tygerberg Hospital, Cape Town, South Africa
| | - Philip A Kalra
- Department of Renal Medicine, Salford Royal NHS Foundation Trust, Salford, UK
| | - Joel R Saldaña
- Resultados Medicos, Desarrollo e Investigación, SC, Boulevard Valle de San Javier, Pachuca Hidalgo, Mexico City, Mexico
| | - Gary Kilov
- University of Melbourne, Launceston, Australia
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Yanai H, Adachi H, Hakoshima M, Katsuyama H. Atherogenic Lipoproteins for the Statin Residual Cardiovascular Disease Risk. Int J Mol Sci 2022; 23:ijms232113499. [PMID: 36362288 PMCID: PMC9657259 DOI: 10.3390/ijms232113499] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 11/01/2022] [Accepted: 11/02/2022] [Indexed: 11/06/2022] Open
Abstract
Randomized controlled trials (RCTs) show that decreases in low-density lipoprotein cholesterol (LDL-C) by the use of statins cause a significant reduction in the development of cardiovascular disease (CVD). However, one of our previous studies showed that, among eight RCTs that investigated the effect of statins vs. a placebo on CVD development, 56–79% of patients had residual CVD risk after the trials. In three RCTs that investigated the effect of a high dose vs. a usual dose of statins on CVD development, 78–87% of patients in the high-dose statin arms still had residual CVD risk. The risk of CVD development remains even when statins are used to strongly reduce LDL-C, and this type of risk is now regarded as statin residual CVD risk. Our study shows that elevated triglyceride (TG) levels, reduced high-density lipoprotein cholesterol (HDL-C), and the existence of obesity/insulin resistance and diabetes may be important metabolic factors that determine statin residual CVD risk. Here, we discuss atherogenic lipoproteins that were not investigated in such RCTs, such as lipoprotein (a) (Lp(a)), remnant lipoproteins, malondialdehyde-modified LDL (MDA-LDL), and small-dense LDL (Sd-LDL). Lp(a) is under strong genetic control by apolipoprotein (a), which is an LPA gene locus. Variations in the LPA gene account for 91% of the variability in the plasma concentration of Lp(a). A meta-analysis showed that genetic variations at the LPA locus are associated with CVD events during statin therapy, independent of the extent of LDL lowering, providing support for exploring strategies targeting circulating concentrations of Lp(a) to reduce CVD events in patients receiving statins. Remnant lipoproteins and small-dense LDL are highly associated with high TG levels, low HDL-C, and obesity/insulin resistance. MDA-LDL is a representative form of oxidized LDL and plays important roles in the formation and development of the primary lesions of atherosclerosis. MDA-LDL levels were higher in CVD patients and diabetic patients than in the control subjects. Furthermore, we demonstrated the atherogenic properties of such lipoproteins and their association with CVD as well as therapeutic approaches.
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Affiliation(s)
- Hidekatsu Yanai
- Correspondence: ; Tel.: +81-473-72-3501; Fax: +81-473-72-1858
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Moriconi D, Nannipieri M, Dadson P, Rosada J, Tentolouris N, Rebelos E. The Beneficial Effects of Bariatric-Surgery-Induced Weight Loss on Renal Function. Metabolites 2022; 12:967. [PMID: 36295869 PMCID: PMC9608617 DOI: 10.3390/metabo12100967] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Revised: 10/08/2022] [Accepted: 10/08/2022] [Indexed: 08/05/2023] Open
Abstract
Obesity represents an independent risk factor for the development of chronic kidney disease (CKD), leading to specific histopathological alterations, known as obesity-related glomerulopathy. Bariatric surgery is the most effective means of inducing and maintaining sustained weight loss. Furthermore, in the context of bariatric-surgery-induced weight loss, a reduction in the proinflammatory state and an improvement in the adipokine profile occur, which may also contribute to the improvement of renal function following bariatric surgery. However, the assessment of renal function in the context of obesity and following marked weight loss is difficult, since the formulas adopted to estimate glomerular function use biomarkers whose production is dependent on muscle mass (creatinine) or adipose tissue mass and inflammation (cystatin-c). Thus, following bariatric surgery, the extent to which reductions in plasma concentrations reflect the actual improvement in renal function is not clear. Despite this limitation, the available literature suggests that in patients with hyperfiltration at baseline, GFR is reduced following bariatric surgery, whereas GFR is increased in patients with decreased GFR at baseline. These findings are also confirmed in the few studies that have used measured rather than estimated GFR. Albuminuria is also decreased following bariatric surgery. Moreover, bariatric surgery seems superior in achieving the remission of albuminuria and early CKD than the best medical treatment. In this article, we discuss the pathophysiology of renal complications in obesity, review the mechanisms through which weight loss induces improvements in renal function, and provide an overview of the renal outcomes following bariatric surgery.
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Affiliation(s)
- Diego Moriconi
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Monica Nannipieri
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Prince Dadson
- Turku PET Centre, University of Turku, 20500 Turku, Finland
| | - Javier Rosada
- Fourth Unit of Internal Medicine, University Hospital of Pisa, 56124 Pisa, Italy
| | - Nikolaos Tentolouris
- Department of Propaedeutic and Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece
| | - Eleni Rebelos
- Turku PET Centre, University of Turku, 20500 Turku, Finland
- Institute of Clinical Physiology, National Research Council (CNR), 56124 Pisa, Italy
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11
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Arjmand MH. The association between visceral adiposity with systemic inflammation, oxidative stress, and risk of post-surgical adhesion. Arch Physiol Biochem 2022; 128:869-874. [PMID: 32141779 DOI: 10.1080/13813455.2020.1733617] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Abdominal and pelvic adhesions are common post-operative complications. Despite new medical technologies, these adhesions are appearing to be unavoidable and little is known about their causation; for example, why certain patients/or tissues are more prone to adhesions. There have been no clinical studies about increasing the risk adhesions in obese patients, but there is some evidence about the molecular mechanisms involving visceral fat (VF) that may lead to profibrotic conditions. VF is an endocrine/inflammatory organ which produces many biologically active molecules such as adipokines and inflammatory cytokines. Inflammatory conditions, oxidative stress, and the expression some fibrotic molecules in the VF may induce pathological conditions in the abdominal cavity that predispose to the formation of fibrotic bands.
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Affiliation(s)
- Mohammad-Hassan Arjmand
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
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12
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Adipokine Levels in Men with Coronary Atherosclerosis on the Background of Abdominal Obesity. J Pers Med 2022; 12:jpm12081248. [PMID: 36013196 PMCID: PMC9409903 DOI: 10.3390/jpm12081248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 07/25/2022] [Accepted: 07/26/2022] [Indexed: 11/17/2022] Open
Abstract
Background. Obesity is associated with dyslipidemia, and excess body fat is associated with unfavorable levels of adipokines and markers of inflammation. The goal of research. To study the level of adipokines and markers of inflammation, their associations with unstable atherosclerotic plaques in men with coronary atherosclerosis on the background of abdominal obesity. Materials and methods. The study involved 82 men aged 40–77 years with coronary atherosclerosis after endarterectomy from the coronary arteries. We divided all men into two groups: 37 men (45.1%) with unstable atherosclerotic plaques, and 45 men (54.9%) who had stable plaques. Obesity was established at a BMI of ≥30 kg/m2. The levels of adipokines and markers of inflammation in the blood were determined by multiplex analysis. Results. In patients with obesity and unstable plaques, the levels of C-peptide, TNFa and IL-6 were 1.8, 1.6, and 2.8 times higher, respectively, than in patients with obesity and stable plaques. The chance of having an unstable plaque increases with an increase in TNFa by 49% in obese patients and decreases with an increase in insulin by 3% in non-obese patients. Conclusions. In men with coronary atherosclerosis and obesity, unstable atherosclerotic plaques in the coronary arteries are directly associated with the level of TNF-α.
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Fischer SV, Appel MH, Naliwaiko K, Pagliosa DD, Araújo DN, Capote AE, Oliveira BAC, Fernandes LC. Early introduction of exercise prevents insulin resistance in postnatal overfed rats. Braz J Med Biol Res 2022; 55:e11987. [PMID: 35857997 PMCID: PMC9296124 DOI: 10.1590/1414-431x2022e11987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 04/27/2022] [Indexed: 11/25/2022] Open
Abstract
Early childhood obesity increases the risk of developing metabolic diseases. We
examined the early introduction of exercise in small-litter obese-induced rats
(SL) on glucose metabolism in the epididymal adipose tissue (AT) and soleus
muscle (SM). On day 3 post-birth, pups were divided into groups of ten or three
(SL). On day 22, rats were split into sedentary (S and SLS) and exercise (E and
SLE) groups. The rats swam three times/week carrying a load for 30 min. In the
first week, they swam without a load; in the 2nd week, they carried a load
equivalent to 2% of their body weight; from the 3rd week to the final week, they
carried a 5% body load. At 85 days of age, an insulin tolerance test was
performed in some rats. At 90 days of age, rats were killed, and blood was
harvested for plasma glucose, cholesterol, and triacylglycerol measurements.
Mesenteric, epididymal, retroperitoneal, and brown adipose tissues were removed
and weighed. SM and AT were incubated in the Krebs-Ringer bicarbonate buffer,
5.5 mM glucose for 1 h with or without 10 mU/mL insulin. Comparison between the
groups was performed by 3-way ANOVA followed by the Tukey
post-hoc test. Sedentary, overfed rats had greater body
mass, more visceral fat, lower lactate production, and insulin resistance. Early
introduction of exercise reduced plasma cholesterol and contained the deposition
of white adipose tissue and insulin resistance. In conclusion, the early
introduction of exercise prevents the effects of obesity on glucose metabolism
in adulthood in this rat model.
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Affiliation(s)
- S V Fischer
- Departamento de Fisiologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, PR, Brasil
| | - M H Appel
- Departamento de Biologia Estrutural, Molecular e Genética, Universidade Estadual de Ponta Grossa, Ponta Grossa, PR, Brasil
| | - K Naliwaiko
- Departamento de Biologia Celular, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, PR, Brasil
| | - D D Pagliosa
- Departamento de Fisiologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, PR, Brasil
| | - D N Araújo
- Departamento de Fisiologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, PR, Brasil
| | - A E Capote
- Departamento de Fisiologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, PR, Brasil
| | - B A C Oliveira
- Departamento de Biologia Celular, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, PR, Brasil
| | - L C Fernandes
- Departamento de Biologia Celular, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, PR, Brasil
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14
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Moriconi D, Antonioli L, Masi S, Bellini R, Pellegrini C, Rebelos E, Taddei S, Nannipieri M. Glomerular hyperfiltration in morbid obesity: Role of the inflammasome signalling. Nephrology (Carlton) 2022; 27:673-680. [PMID: 35681274 DOI: 10.1111/nep.14077] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 05/18/2022] [Accepted: 06/02/2022] [Indexed: 01/08/2023]
Abstract
AIM Obesity is associated with glomerular hyperfiltration which may precede the development of overt renal damage. Few studies evaluated the link between inflammasome signalling and hyperfiltration. The aim is to evaluate the relationship between IL1-β/Caspase-1, insulin sensitivity and hyperfiltration in subjects with severe obesity, before and after weight loss. METHODS Forty-six patients with BMI > 35 kg/m2 , without type-2-diabetes or hypertension, were evaluated at baseline and 6 months after bariatric surgery with oral glucose tollerance test, bioimpedance analysis and blood tests. The eGFR was calculated according to EPIcr-cys formula and insulin sensitivity by Oral Glucose Insulin Sensitivity. IL-1β/Caspase-1 were measured with the ELISA-kit. HF was defined as eGFR ≥ 140 ml/min (non-indexed for BSA). RESULTS Sixteen subjects at baseline had hyperfiltration, with a higher insulin resistance, BMI, lean mass and plasma levels of IL-1β/Caspase-1. After surgery, there was a reduction in BMI and improvement in insulin resistance in all patients. However, in 8 of 16 patients hyperfiltration persisted and IL-1β/Caspase-1 levels did not decrease (3.22 ± 0.79 vs. 3.13 ± 1.03 and 23.7 ± 12.1 vs. 20.6 ± 9.1, pre vs. post, pg/ml), while cytokines normalized in all the other patients in parallel with the eGFR. In a logistic regression model, correcting for the main covariates, lean mass and IL-1β before surgery (p = .01 and p = .03, respectively), were the only predictors of hyperfiltration. CONCLUSION Weight loss is effective in reducing hyperfiltration in most, but not all patients. Hyperfiltration remains unchanged in subjects who do not have a reduction in IL-1β/Caspase-1, suggesting a pathogenetic role of the inflammasome signalling in the early stages of nephropathy.
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Affiliation(s)
- Diego Moriconi
- Department of Surgical, Medical, Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| | - Luca Antonioli
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Stefano Masi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | | | - Carolina Pellegrini
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Eleni Rebelos
- Institute of Clinical Physiology, National Research Council (CNR), Pisa, Italy
| | - Stefano Taddei
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Monica Nannipieri
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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15
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Mohan J, Ghazi T, Chuturgoon AA. A Critical Review of the Biochemical Mechanisms and Epigenetic Modifications in HIV- and Antiretroviral-Induced Metabolic Syndrome. Int J Mol Sci 2021; 22:ijms222112020. [PMID: 34769448 PMCID: PMC8584285 DOI: 10.3390/ijms222112020] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/24/2021] [Accepted: 09/27/2021] [Indexed: 02/07/2023] Open
Abstract
Metabolic syndrome (MetS) is a non-communicable disease characterised by a cluster of metabolic irregularities. Alarmingly, the prevalence of MetS in people living with Human Immunodeficiency Virus (HIV) and antiretroviral (ARV) usage is increasing rapidly. This study aimed to look at biochemical mechanisms and epigenetic modifications associated with HIV, ARVs, and MetS. More specifically, emphasis was placed on mitochondrial dysfunction, insulin resistance, inflammation, lipodystrophy, and dyslipidaemia. We found that mitochondrial dysfunction was the most common mechanism that induced metabolic complications. Our findings suggest that protease inhibitors (PIs) are more commonly implicated in MetS-related effects than other classes of ARVs. Furthermore, we highlight epigenetic studies linking HIV and ARV usage to MetS and stress the need for more studies, as the current literature remains limited despite the advancement in and popularity of epigenetics.
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16
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Poessel M, Morys F, Breuer N, Villringer A, Hummel T, Horstmann A. Brain response to food odors is not associated with body mass index and obesity-related metabolic health measures. Appetite 2021; 168:105774. [PMID: 34715246 DOI: 10.1016/j.appet.2021.105774] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 09/17/2021] [Accepted: 10/22/2021] [Indexed: 12/14/2022]
Abstract
Smell perception plays a role in eating behavior and might be involved in the development of obesity. In fact, olfactory function is impaired in obesity and might depend on metabolic health factors. To date, the underlying neural mechanisms remain unclear. Here, we investigate neural processing of food-related odors in normal-weight, overweight and obese individuals. Fifty-three young and healthy participants (28.8 ± 4.4 years, 27 female; 24 normal-weight, 10 overweight, and 19 obese) were presented with high- (chocolate, potato chips) and low-caloric (orange, cucumber) food odors during a functional magnetic resonance imaging (fMRI). We also assessed olfactory identification ability, body mass index (BMI), body fat percentage, insulin resistance, and leptin levels. In brief, olfactory perception of food odors was linked to brain activity in the entorhinal and piriform cortex, and the insula, hippocampus, and amygdala. Insulin resistance was negatively related to olfactory identification. Additionally, perception of sweet versus savory odors was related to a higher brain activity in the right middle/superior frontal gyrus. Finally, we found no effect of obesity status, BMI, metabolic factors, or body fat percentage on neural responses to food odors. Overall, this suggests that food odor processing might depend on factors other than body weight status or associated markers of metabolic health.
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Affiliation(s)
- Maria Poessel
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103, Leipzig, Germany; IFB AdiposityDiseases, Leipzig University Medical Center, Philipp-Rosenthal-Str. 27, 04103, Leipzig, Germany.
| | - Filip Morys
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103, Leipzig, Germany; Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC, H3A 2B4, Canada
| | - Nora Breuer
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103, Leipzig, Germany; IFB AdiposityDiseases, Leipzig University Medical Center, Philipp-Rosenthal-Str. 27, 04103, Leipzig, Germany
| | - Arno Villringer
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103, Leipzig, Germany; Day Clinic for Cognitive Neurology, University Hospital at the University of Leipzig, Liebigstraße 16, 04103, Leipzig, Germany; Mind Brain Body Institute, Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, 10099, Berlin, Germany; Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany; International Max Planck Research School on the Life Course, Max Planck Institute for Human Development, Lentzeallee 94, 14195, Berlin, Germany; International Max Planck Research School on the Neuroscience of Communication, Max Planck Institute for Human Cognitive and Brain Sciences, P.O. Box 500355, 04103, Leipzig, Germany
| | - Thomas Hummel
- Smell & Taste Clinic, Department of Otorhinolaryngology, TU Dresden, Fetscherstrasse 74, 01307, Dresden, Germany
| | - Annette Horstmann
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1a, 04103, Leipzig, Germany; IFB AdiposityDiseases, Leipzig University Medical Center, Philipp-Rosenthal-Str. 27, 04103, Leipzig, Germany; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Haartmaninkatu 3, 00290, Helsinki, Finland
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17
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Leite NN, Cota BC, Gotine AREM, Rocha DMUP, Pereira PF, Hermsdorff HHM. Visceral adiposity index is positively associated with blood pressure: A systematic review. Obes Res Clin Pract 2021; 15:546-556. [PMID: 34696990 DOI: 10.1016/j.orcp.2021.10.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 09/20/2021] [Accepted: 10/09/2021] [Indexed: 10/20/2022]
Abstract
PURPOSE This systematic review aimed to investigate the association between VAI and blood pressure. METHODS The study was according to the PRISMA standards and the bibliographic search in the PubMed, EMBASE and Cochrane Library databases. RESULTS This review included 32 articles, with 60,482 individuals - children to elderly people between 7 and 102 years old - of different age groups, most of them female (54.9%; n = 26,478). The year of publication ranged from 2010 to 2020, indicating that it is a recent theme, applied in almost all continents (America, Europe, Africa and Asia). The authors used data as continuous or into quantiles; blood pressure data also varied, with different cutoff points for the classification of arterial hypertension or continuously. The vast majority of studies have shown a positive association between VAI and blood pressure, both the sexes, in different age groups. The evaluation of the quality of the articles used by the Tool of the Joanna Briggs Institute according to their design. CONCLUSION Individuals with increased VAI have higher blood pressure levels. Registration (PROSPERO: CRD42020205965).
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Affiliation(s)
- Nathália Nogueira Leite
- Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil.
| | - Bruna Clemente Cota
- Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil
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18
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Parent C, Pokhvisneva I, de Mendonça Filho EJ, O'Donnell KJ, Meaney MJ, Kee MZL, Thng G, Wing H, Adler NE, Keeton V, Pantell MS, Hessler D, Gottlieb LM, Silveira PP. Salivary cytokine cluster moderates the association between caregivers perceived stress and emotional functioning in youth. Brain Behav Immun 2021; 94:125-137. [PMID: 33662503 DOI: 10.1016/j.bbi.2021.02.025] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 02/14/2021] [Accepted: 02/24/2021] [Indexed: 10/22/2022] Open
Abstract
Some individuals exposed to early life stress show evidence of enhanced systemic inflammation and are at greater risk for psychopathology. In the current study, caregivers and their offspring (0-17 years) were recruited at a pediatric clinic visit at the University of California, San Francisco (UCSF). Mothers and seven-year-old children from the Growing Up inSingaporeTowards healthy Outcomes (GUSTO) prospective birth cohort were used as a replication cohort. Caregivers perceived stress was measured to determine potential intergenerational effects on the children's functioning and inflammation levels. Children's emotional functioning in the UCSF cohort was evaluated using the Pediatric Quality of Life (PedsQL) inventory. Child emotional and behavioral functioning was measured using the Child Behavior Checklist (CBCL) in GUSTO. Saliva was collected from the children and salivary levels of IL-6, IL-1β, IL-8 and TNF-α were measured using an electrochemiluminescent cytokine multiplex panel. Child IL-6, IL-1β, IL-8 cytokine levels were clustered into low, average, and high cytokine cluster groups using hierarchical cluster analysis. We did not find that salivary cytokine clusters were significantly associated with children's emotional or behavioral function. However, cytokine clusters did significantly moderate the association between increased caregiver perceived stress and reduced child emotional functioning (UCSF cohort) and increased Attention-Deficit-Hyperactivity (ADH) problems (GUSTO cohort, uncorrected Cohen's F2 = 0.02). Using a cytokine clustering technique may be useful in identifying those children exposed to increased caregiver perceived stress that are at risk of emotional and attention deficit hyperactivity problems.
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Affiliation(s)
- Carine Parent
- Douglas Mental Health University Institute, Douglas Research Center, McGill University, Montreal, QC, Canada
| | - Irina Pokhvisneva
- Douglas Mental Health University Institute, Douglas Research Center, McGill University, Montreal, QC, Canada
| | | | - Kieran J O'Donnell
- Douglas Mental Health University Institute, Douglas Research Center, McGill University, Montreal, QC, Canada; Ludmer Centre for Neuroinformatics and Mental Health and Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, QC, Canada; CIFAR, Toronto, ON, Canada; Yale Child Study Center & Department of Obstetrics Gynecology & Reproductive Sciences, Yale School of Medicine, Yale University, New Haven, CT, USA
| | - Michael J Meaney
- Douglas Mental Health University Institute, Douglas Research Center, McGill University, Montreal, QC, Canada; Ludmer Centre for Neuroinformatics and Mental Health and Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, QC, Canada; Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore; CIFAR, Toronto, ON, Canada
| | - Michelle Z L Kee
- Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore
| | - Gladi Thng
- Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore
| | - Holly Wing
- University of California, San Francisco, Center for Health and Community, San Francisco, CA, United States
| | - Nancy E Adler
- University of California, San Francisco, Department of Psychiatry and Pediatrics, San Francisco, CA, United States
| | - Victoria Keeton
- University of California, San Francisco, Family Health Care Nursing, School of Nursing, San Francisco, CA, United States
| | - Matthew S Pantell
- University of California, San Francisco, Department of Pediatrics, School of Medicine, San Francisco, CA, United States
| | - Danielle Hessler
- University of California, San Francisco, Department of Family and Community Medicine, San Francisco, CA, United States
| | - Laura M Gottlieb
- University of California, San Francisco, Department of Family and Community Medicine, San Francisco, CA, United States
| | - Patricia P Silveira
- Douglas Mental Health University Institute, Douglas Research Center, McGill University, Montreal, QC, Canada; Ludmer Centre for Neuroinformatics and Mental Health and Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, QC, Canada.
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19
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Ramon-Krauel M, Leal-Witt MJ, Osorio-Conles Ó, Amat-Bou M, Lerin C, Selva DM. Relationship between adiponectin, TNFα, and SHBG in prepubertal children with obesity. Mol Cell Pediatr 2021; 8:3. [PMID: 33689083 PMCID: PMC7947057 DOI: 10.1186/s40348-021-00113-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 03/01/2021] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Sex hormone-binding globulin (SHBG) levels are low in adult subjects with obesity when compared to normal-weight individuals. Obesity is associated with higher tumor necrosis factor alpha (TNFα) plasma levels and lower adiponectin levels. Moreover, we have recently elucidated the molecular mechanisms by which TNFα and adiponectin regulate hepatic SHBG production. AIM The main objective of this study was to assess if the adult associations between TNFα, adiponectin, and SHBG are present in prepubertal children. METHODS We determined several morphometric and biochemical parameters in normal-weight (n=15) and obese prepubertal (n=51) children, as well as quantified plasma SHBG, TNFα receptor 1 (TNFα-R1), and adiponectin levels. RESULTS Our results showed that prepubertal children with obesity had decreased plasma SHBG levels compared to normal-weight controls (67 nmol/L vs 172 nmol/L). Importantly, SHBG plasma levels correlated significantly (P < 0.05) with TNFα (negatively, ßstd= - 0.31) and adiponectin (positively, ßstd= 0.58) suggesting an important role of these two cytokines in determining plasma SHBG levels in prepubertal children. CONCLUSIONS Our results suggest that plasma adiponectin levels may play a more important role than TNFα in influencing plasma SHBG levels in our prepubertal population with obesity.
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Affiliation(s)
- Marta Ramon-Krauel
- Endocrinology Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, 08950, Barcelona, Spain
| | - María Jesús Leal-Witt
- Endocrinology Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, 08950, Barcelona, Spain
| | - Óscar Osorio-Conles
- Endocrinology Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, 08950, Barcelona, Spain
| | - Montse Amat-Bou
- Endocrinology Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, 08950, Barcelona, Spain
| | - Carles Lerin
- Endocrinology Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, 08950, Barcelona, Spain.
| | - David M Selva
- Diabetes and Metabolism Research Unit, Vall Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Pg Vall d'Hebron 119-129, 08035, Barcelona, Spain.
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20
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Cohen E, Margalit I, Shochat T, Goldberg E, Krause I. Markers of Chronic Inflammation in Overweight and Obese Individuals and the Role of Gender: A Cross-Sectional Study of a Large Cohort. J Inflamm Res 2021; 14:567-573. [PMID: 33658829 PMCID: PMC7920597 DOI: 10.2147/jir.s294368] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 02/13/2021] [Indexed: 01/08/2023] Open
Abstract
Objective During the last decade, obesity has become an epidemic. As obesity is now considered a state of low-grade inflammation, the purpose of this study was to assess the prevalence of four common elements of inflammation, in individuals with increased BMI. These findings were compared to those of subjects with normal BMI. The effect of gender was also noted. Methods Data were collected from medical records of individuals examined at a screening center in Israel between the years 2000–2014. Cross-sectional analysis was carried out on 7526 men and 3219 women. White blood cell count (WBC); platelet (PLT) count; erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were assessed in four BMI categories: normal, overweight, obese and morbidly obese. Results Mean (SD) age of the study sample was 47.5 (9.7) and 46.7 (9.8) years for men and women, respectively. The prevalence of each inflammatory marker increased significantly when comparing abnormal to normal BMI (p<0.0001). The odds ratio (OR) of the prevalence of increased inflammatory markers was compared between subjects with overweight, obese and morbid obesity and subjects with normal BMI. This study showed that the higher the BMI, the higher the OR. For those in the morbid obesity group, the OR for the different inflammatory markers adjusting for age, diabetes mellitus hypertension and kidney function were as follows: WBC levels, 5.1 (2.9–8.7) and 4.7 (2.4–9.1) for men and women, respectively; PLT levels, 1.7 (0.3–8.5) and 2.0 (0.6–7.2) for men and women, respectively; ESR levels, 4.2 (3.2–5.4) and 4.6 (3.2–6.6) for men and women, respectively, and CRP levels, 13.4 (10.0–18.2) and 19.2 (12.9–28.6) for men and women, respectively. Conclusion Inflammatory markers are significantly higher in subjects with abnormal compared to normal BMI. This difference was found to be greater in women than in men.
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Affiliation(s)
- Eytan Cohen
- Department of Medicine F - Recanati, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
| | - Ili Margalit
- Department of Medicine F - Recanati, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
| | - Tzippy Shochat
- Statistical Counselling Unit, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
| | - Elad Goldberg
- Department of Medicine F - Recanati, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
| | - Ilan Krause
- Department of Medicine F - Recanati, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
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21
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Obesity-Related Endothelial Dysfunction: moving from classical to emerging mechanisms. ENDOCRINE AND METABOLIC SCIENCE 2020. [DOI: 10.1016/j.endmts.2020.100063] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
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22
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Arabzadegan N, Daneshzad E, Fatahi S, Moosavian SP, Surkan PJ, Azadbakht L. Effects of dietary whole grain, fruit, and vegetables on weight and inflammatory biomarkers in overweight and obese women. Eat Weight Disord 2020; 25:1243-1251. [PMID: 31399910 DOI: 10.1007/s40519-019-00757-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 07/19/2019] [Indexed: 12/27/2022] Open
Abstract
PURPOSE The separate effects of whole grain (WG) and fruit and vegetable (F&V) diets on inflammatory biomarkers have not been assessed. Therefore, we evaluated these two high-fiber diets in relation to inflammation indices in obese and overweight women. STUDY DESIGN Parallel randomized clinical trial. METHODS In the present study, 75 women were recruited and randomly assigned to three diet groups: a whole grain diet (WG-D) group, F&V group, and a combined whole grain and F&V diet group (WGFV-D) for 10 weeks. As a "feeding trial" all participants were asked to visit the clinic daily and eat prescribed foods in the presence of a nutritionist. Anthropometric indices and biochemical biomarkers were measured at baseline and after 10 weeks of the trial. RESULTS Each of the three diet groups showed significant changes in serum biomarkers (CRP, TNF-α, IL-6, D-dimer, and serum fibrinogen) after following the diet for 10 weeks (P = 0.01). In adjusted models, significant changes were observed for CRP, TNF-α, IL-6, D-dimer, and serum fibrinogen (P = 0.01). In a model adjusted for malondialdehyde (MDA) level, a trend toward significance was observed (P = 0.05). Consumption of all three different diets for 10 weeks showed statistically significant change for all biomarkers (P < 0.05) the most notable changes in inflammatory indices were observed among participants following the WG diet. CONCLUSIONS Study results indicate that consumption of high-fiber diets, especially the WG diet, can help lower inflammatory levels and prevent subsequent adverse health consequences. LEVEL OF EVIDENCE Level I, randomized controlled trial.
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Affiliation(s)
- Niloufar Arabzadegan
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Elnaz Daneshzad
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Somayeh Fatahi
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyedeh Parisa Moosavian
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Pamela J Surkan
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Leila Azadbakht
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
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23
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Casein glycomacropeptide is well tolerated in healthy adults and changes neither high-sensitive C-reactive protein, gut microbiota nor faecal butyrate: a restricted randomised trial. Br J Nutr 2020; 125:1374-1385. [PMID: 32967742 DOI: 10.1017/s0007114520003736] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Casein glycomacropeptide (CGMP) is a bioactive milk-derived peptide with potential anti-inflammatory effects. Animal studies suggest that CGMP may work by altering gut microbiota composition and enhancing butyrate production. Its effects on intestinal homoeostasis, microbiota and metabolites in humans are unknown. The aim of the present study was to assess both the intestinal and systemic immunomodulatory effects of orally ingested CGMP. We hypothesised that daily oral CGMP intake would reduce high-sensitive C-reactive protein (hsCRP) in healthy adults. In a single-centre limited but randomised, double-blinded, reference-controlled study, we compared the effects of a 4-week intervention of either 25 g of oral powder-based chocolate-flavoured CGMP or a reference drink. We included twenty-four healthy adults who all completed the study. CGMP had no systemic or intestinal immunomodulatory effects compared with a reference drink, with regard to either hsCRP or faecal calprotectin level, faecal microbiota composition or faecal SCFA content. CGMP ingestion did not affect satiety or body weight, and it caused no severe adverse events. The palatability of CGMP was acceptable, and adherence was high. CGMP did not induce or change gastrointestinal symptoms. In conclusion, we found no immunomodulatory effects of CGMP in healthy adults. In a minor group of healthy adults, oral ingestion of 25 g of CGMP during 4 weeks was safe, well tolerated, had acceptable palatability and was without any effects on body weight.
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Oxidative Stress and New Pathogenetic Mechanisms in Endothelial Dysfunction: Potential Diagnostic Biomarkers and Therapeutic Targets. J Clin Med 2020; 9:jcm9061995. [PMID: 32630452 PMCID: PMC7355625 DOI: 10.3390/jcm9061995] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 06/15/2020] [Accepted: 06/23/2020] [Indexed: 02/07/2023] Open
Abstract
Cardiovascular diseases (CVD), including heart and pathological circulatory conditions, are the world's leading cause of mortality and morbidity. Endothelial dysfunction involved in CVD pathogenesis is a trigger, or consequence, of oxidative stress and inflammation. Endothelial dysfunction is defined as a diminished production/availability of nitric oxide, with or without an imbalance between endothelium-derived contracting, and relaxing factors associated with a pro-inflammatory and prothrombotic status. Endothelial dysfunction-induced phenotypic changes include up-regulated expression of adhesion molecules and increased chemokine secretion, leukocyte adherence, cell permeability, low-density lipoprotein oxidation, platelet activation, and vascular smooth muscle cell proliferation and migration. Inflammation-induced oxidative stress results in an increased accumulation of reactive oxygen species (ROS), mainly derived from mitochondria. Excessive ROS production causes oxidation of macromolecules inducing cell apoptosis mediated by cytochrome-c release. Oxidation of mitochondrial cardiolipin loosens cytochrome-c binding, thus, favoring its cytosolic release and activation of the apoptotic cascade. Oxidative stress increases vascular permeability, promotes leukocyte adhesion, and induces alterations in endothelial signal transduction and redox-regulated transcription factors. Identification of new endothelial dysfunction-related oxidative stress markers represents a research goal for better prevention and therapy of CVD. New-generation therapeutic approaches based on carriers, gene therapy, cardiolipin stabilizer, and enzyme inhibitors have proved useful in clinical practice to counteract endothelial dysfunction. Experimental studies are in continuous development to discover new personalized treatments. Gene regulatory mechanisms, implicated in endothelial dysfunction, represent potential new targets for developing drugs able to prevent and counteract CVD-related endothelial dysfunction. Nevertheless, many challenges remain to overcome before these technologies and personalized therapeutic strategies can be used in CVD management.
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Sharath SS, Ramu J, Nair SV, Iyer S, Mony U, Rangasamy J. Human Adipose Tissue Derivatives as a Potent Native Biomaterial for Tissue Regenerative Therapies. Tissue Eng Regen Med 2020; 17:123-140. [PMID: 31953618 PMCID: PMC7105544 DOI: 10.1007/s13770-019-00230-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 11/07/2019] [Accepted: 11/15/2019] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Human adipose tissue is a great source of translatable biomaterials owing to its ease of availability and simple processing. Reusing discardable adipose tissue for tissue regeneration helps in mimicking the exact native microenvironment of tissue. Over the past 10 years, extraction, processing, tuning and fabrication of adipose tissue have grabbed the attention owing to their native therapeutic and regenerative potential. The present work gives the overview of next generation biomaterials derived from human adipose tissue and their development with clinical relevance. METHODS Around 300 articles have been reviewed to widen the knowledge on the isolation, characterization techniques and medical applications of human adipose tissue and its derivatives from bench to bedside. The prospective applications of adipose tissue derivatives like autologous fat graft, stromal vascular fraction, stem cells, preadipocyte, adipokines and extracellular matrix, their behavioural mechanism, rational property of providing native bioenvironment, circumventing their translational abilities, recent advances in featuring them clinically have been reviewed extensively to reveal the dormant side of human adipose tissue. RESULTS Basic understanding about the molecular and structural aspect of human adipose tissue is necessary to employ it constructively. This review has nailed the productive usage of human adipose tissue, in a stepwise manner from exploring the methods of extracting derivatives, concerns during processing and its formulations to turning them into functional biomaterials. Their performance as functional biomaterials for skin regeneration, wound healing, soft tissue defects, stem cell and other regenerative therapies under in vitro and in vivo conditions emphasizes the translational efficiency of adipose tissue derivatives. CONCLUSION In the recent years, research interest has inclination towards constructive tissue engineering and regenerative therapies. Unravelling the maximum utilization of human adipose tissue derivatives paves a way for improving existing tissue regeneration and cellular based therapies and other biomedical applications.
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Affiliation(s)
- Siva Sankari Sharath
- Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041, India
| | - Janarthanan Ramu
- Department of Plastic and Reconstructive Surgery, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041, India
| | - Shantikumar Vasudevan Nair
- Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041, India
| | - Subramaniya Iyer
- Department of Plastic and Reconstructive Surgery, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041, India
| | - Ullas Mony
- Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041, India.
| | - Jayakumar Rangasamy
- Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041, India.
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Antonioli L, Moriconi D, Masi S, Bottazzo D, Pellegrini C, Fornai M, Anselmino M, Ferrannini E, Blandizzi C, Taddei S, Nannipieri M. Differential Impact of Weight Loss and Glycemic Control on Inflammasome Signaling. Obesity (Silver Spring) 2020; 28:609-615. [PMID: 32020775 DOI: 10.1002/oby.22734] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 12/03/2019] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Interleukin (IL)-1β is involved in obesity-associated inflammation and in the pathogenesis of type 2 diabetes (T2D) mellitus. Our aim was to correlate serum IL-1β and caspase-1 levels with weight loss, glucose metabolism, and insulin resistance (IR) after bariatric surgery. METHODS A total of 32 patients with morbid obesity and T2D (Ob-T2D) and 29 patients with morbid obesity and normal glucose tolerance (Ob-NGT), treated by Roux-en-Y gastric bypass, were studied before and 1 year after surgery. Sixteen healthy individuals served as a control (HC) group. IR was assessed by the oral glucose insulin sensitivity method. Plasma IL-1β levels and caspase-1 were measured. RESULTS Presurgery BMI was similar in Ob-NGT and Ob-T2D. IR was progressively impaired in Ob-NGT and Ob-T2D (P < 0.0001). Fasting plasma IL-1β and caspase-1 levels were lower in HCs than in patients with Ob-NGT or Ob-T2D (P < 0.02; P = 0.05), and both were inversely correlated with IR (P = 0.01; P = 0.02). After surgery, BMI decreased and IR improved to a similar extent in Ob-NGT and Ob-T2D (P < 0.0001). Plasma caspase-1 concentrations normalized in both groups (P < 0.0001), whereas plasma IL-1β levels normalized only in Ob-NGT. CONCLUSIONS Plasma IL-1β and caspase-1 levels were inversely correlated with IR. Caspase-1 levels normalized after weight loss, whereas IL-1β normalized only in people without T2D, suggesting the persistence of a systemic inflammatory condition in people with T2D.
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Affiliation(s)
- Luca Antonioli
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Diego Moriconi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Stefano Masi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Dario Bottazzo
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Carolina Pellegrini
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Matteo Fornai
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Marco Anselmino
- Division of Bariatric Surgery, Azienda Ospedaliera Universitaria Pisana (AOUP), Pisa, Italy
| | - Ele Ferrannini
- National Research Council Institute of Clinical Physiology, Pisa, Italy
| | - Corrado Blandizzi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Stefano Taddei
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Monica Nannipieri
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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Martikainen TA, Teppo AM, Grönhagen–Riska C, Ekstrand AV. Glucose-Free Dialysis Solutions: Inductors of Inflammation or Preservers of Peritoneal Membrane? Perit Dial Int 2020. [DOI: 10.1177/089686080502500509] [Citation(s) in RCA: 61] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Objectives Glucose and other bioincompatible factors of conventional peritoneal dialysis solutions may damage the peritoneal membrane. The aim of our study was to investigate whether replacement of glucose with icodextrin (ID) or amino acids (AA) affects inflammatory parameters or cancer antigen 125 (CA125). Design Either ID or AA was used, in random order, in one daily exchange during an 8-week period. After the first study period, the patients entered a washout period and then switched to the other study solution for an 8-week period. C-reactive protein (CRP) was measured in serum, and CA125, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), and hyaluronan (HA) were measured in the overnight dwell dialysates at the beginning and end of the study periods. Setting A university hospital. Patients 22 patients with duration on peritoneal dialysis of 1.5 – 6.3 months. Main Outcome Measures Levels of serum CRP and dialysate CA125, IL-6, HA, and sICAM-1 during use of ID and AA were compared to levels during use of glucose-only-based solutions. Results CRP increased significantly during use of ID. CA125 increased significantly during 8 weeks’ use of AA, from 22.8 (5.4 – 89.0) to 42.9 (7.1 – 92.9) kU/L ( p = 0.007). IL-6 increased during 8 weeks’ use of AA, from 22.0 (9.0 – 108.0) to 36.5 (14.0 – 93.0) ng/L ( p = 0.002) and ID, from 25.5 (8.0 – 82.0) to 40.0 (12.0 – 118.0) ng/L ( p = 0.008). TNF-α also increased significantly during use of ID, but showed no significant changes during use of AA. Conclusions The use of glucose-free solutions, especially AA, may lead to preservation of mesothelial cell mass and host defense. However, activation of systemic and peritoneal inflammation may appear during the use of ID and to a lesser extent during use of AA.
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Affiliation(s)
- Terhi A. Martikainen
- Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
| | - Anna-Maija Teppo
- Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
| | - Carola Grönhagen–Riska
- Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
| | - Agneta V. Ekstrand
- Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
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Femminò S, Pagliaro P, Penna C. Obesity and Cardioprotection. Curr Med Chem 2020; 27:230-239. [DOI: 10.2174/0929867326666190325094453] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Revised: 06/05/2018] [Accepted: 12/24/2018] [Indexed: 01/21/2023]
Abstract
The incidence of obesity and diabetes is increasing rapidly worldwide. Obesity and
metabolic syndrome are strictly linked and represent the basis of different cardiovascular risk
factors, including hypertension and inflammatory processes predisposing to ischemic heart
disease, which represent the most common causes of heart failure. Recent advances in the understanding
of ischemia/reperfusion mechanisms of injury and mechanisms of cardioprotection
are briefly considered. Resistance to cardioprotection may be correlated with the severity
of obesity. The observation that heart failure obese patients have a better clinical condition
than lean heart failure patients is known as “obesity paradox”. It seems that obese patients
with heart failure are younger, making age the most important confounder in some studies.
Critical issues are represented by the "obesity paradox” and heart failure exacerbation by inflammation.
For heart failure exacerbation by inflammation, an important role is played by
NLRP3 inflammasome, which is emerging as a possible target for heart failure condition.
These critical issues in the field of obesity and cardiovascular diseases need more studies to
ascertain which metabolic alterations are crucial for alleged beneficial and deleterious effects
of obesity.
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Affiliation(s)
- Saveria Femminò
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Pasquale Pagliaro
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Claudia Penna
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
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Abstract
The paper is based on the lecture that I gave on receiving the Nutrition Society's inaugural Gowland Hopkins Award for contributions to Cellular and Molecular Nutrition. It reviews studies on the adipose tissues, brown and white, conducted by the groups that I have led since entering nutrition research in 1975. The initial focus was on exploring metabolic factors that underpin the development of obesity using animal models. This resulted in an interest in non-shivering thermogenesis with brown adipose tissue being identified as the key effector of facultative heat production. Brown fat is less thermogenically active in various obese rodents, and major changes in activity are exhibited under physiological conditions such as lactation and fasting consistent with a general role for the tissue in nutritional energetics. My interests moved to white adipose tissue following the cloning of the Ob gene. Our initial contributions in this area included demonstrating nutritional regulation of Ob gene expression and circulating leptin levels, as well as a regulatory role for the sympathetic nervous system operating through β3-adrenoceptors. My interests subsequently evolved to a wider concern with the endocrine/signalling role of adipose tissue. Inflammation is a characteristic of white fat in obesity with the release of inflammation-related adipokines, and we proposed that hypoxia underlies this inflammatory state. O2-deprivation was shown to have substantial effects on gene expression and cellular function in white adipocytes. The hypoxia studies led to the proposition that O2 should be considered as a critical macronutrient.
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Burne G, Mansfield M, Gaida JE, Lewis JS. Is there an association between metabolic syndrome and rotator cuff-related shoulder pain? A systematic review. BMJ Open Sport Exerc Med 2019; 5:e000544. [PMID: 31921436 PMCID: PMC6937110 DOI: 10.1136/bmjsem-2019-000544] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/03/2019] [Indexed: 12/13/2022] Open
Abstract
Objectives Rotator cuff-related shoulder pain (RCRSP) is a common upper limb complaint. It has been suggested that this condition is more common among people with cardiometabolic risk factors. This systematic review has synthesised evidence from case–control, cross-sectional and cohort studies on the association between metabolic syndrome (MetS) and RCRSP. Design and data sources Five medical databases (MEDLINE, EMBASE, SCOPUS, CINAHL and AMED) and reference checking methods were used to identify all relevant English articles that considered MetS and RCRSP. Studies were appraised using the Newcastle-Ottawa Scale (NOS). Two reviewers performed critical appraisal and data extraction. Narrative synthesis was performed via content analysis of statistically significant associations. Results Three cross-sectional, two case–control and one cohort study met the inclusion criteria, providing a total of 1187 individuals with RCRSP. Heterogeneity in methodology and RCRSP or MetS definition precluded a meaningful meta-analysis. Four of the included studies identified associations between the prevalence of MetS and RCRSP. Studies consistently identified independent cardiometabolic risk factors associated with RCRSP. All studies were level III evidence. Summary and conclusion The low-moderate quality evidence included in this review suggests an association between MetS and RCRSP. Most studies demonstrated moderate quality on appraisal. The direction of association and cardiometabolic factors influencing should be investigated by longitudinal and treatment studies. These preliminary conclusions and clinical utility should be treated with caution due to limitations of the evidence base.
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Affiliation(s)
- Graham Burne
- Physiotherapy Department, Guy's and Saint Thomas' NHS Foundation Trust, London, UK.,Physiotherapy, University of Hertfordshire School of Health and Social Work, Hatfield, UK
| | - Michael Mansfield
- Allied Health Sciences, School of Health and Social Care, London Southbank University, London, UK
| | - Jamie E Gaida
- Research Institute for Sport and Exercise (UCRISE), University of Canberra, Canberra, Australian Capital Territory, Australia
| | - Jeremy S Lewis
- School of Health and Social Work, University of Hertfordshire, Hatfield, UK.,Therapy Department, Central London Community Healthcare National Health Service Trust, London, UK.,Department of Physical Therapy and Rehabilitation Science, College of Health Sciences, Qatar University, Doha, Qatar
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Huang X, Ye Q, Zhu Z, Chen W, Chen Y, Li J, Sun J, Ye Z. Association between a functional interleukin 6 receptor genetic variant and the risk and functional outcome of large artery atherosclerotic stroke. Int J Neurosci 2019; 130:355-362. [PMID: 31679401 DOI: 10.1080/00207454.2019.1688810] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Purpose: To investigate whether the Asp358Ala of interleukin 6 receptor related to the risk and outcome of large artery atherosclerotic (LAA) stroke in Han Chinese.Materials and methods: A prospective cohort study was conducted on 768 patients with LAA stroke and 686 non-stroke controls. The genotypes of Asp358Ala polymorphism were determined using SNPscan technology. Associations between genotypes and the risk of LAA stroke were analyzed with logistic regression model.Results: CC genotype (P < 0.001) and AC genotype (P = 0.023) decreased the risk of LAA stroke compared with AA genotype. Multivariate logistic regression analysis revealed that CC genotype was significantly associated with the risk of LAA stroke (P = 0.002). In the subgroup analyses, polymorphisms of Asp358Ala were significantly associated with the risk of LAA stroke in additive model, dominant model and recessive model (P = 0.009, P = 0.017, P = 0.012, respectively) for male, but not for female. Further regression analysis showed that compared with participants with AA genotype and obesity, participants with CC genotype and non-obesity were less likely to suffer LAA stroke (P = 0.003). For male participants, these associations were still existed (additive model, P = 0.022). After 3-month follow-up, patients with C allele had good functional prognosis compared with patients with A allele (P = 0.009).Conclusion: The study demonstrated that the Asp358Ala polymorphism might be associated with susceptibility to the development and outcome of LAA stroke in Han Chines.
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Affiliation(s)
- Xiaoya Huang
- Department of Neurology, Wenzhou Central Hospital & Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, Zhejiang, PR China
| | - Qiang Ye
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China
| | - Zhenguo Zhu
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China
| | - Wei Chen
- Department of Radiology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China
| | - Yanyan Chen
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China
| | - Jia Li
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China
| | - Jun Sun
- Department of Neurosurgery, Wenzhou Central Hospital & Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, Zhejiang, PR China
| | - Zusen Ye
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China
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Nordic Diet and Inflammation-A Review of Observational and Intervention Studies. Nutrients 2019; 11:nu11061369. [PMID: 31216678 PMCID: PMC6627927 DOI: 10.3390/nu11061369] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 06/07/2019] [Accepted: 06/14/2019] [Indexed: 12/21/2022] Open
Abstract
Low-grade inflammation (LGI) has been suggested to be involved in the development of chronic diseases. Healthy dietary patterns, such as the Mediterranean diet (MD), may decrease the markers of LGI. Healthy Nordic diet (HND) has many similarities with MD, but its effects on LGI are less well known. Both of these dietary patterns emphasize the abundant use of fruits and vegetables (and berries in HND), whole grain products, fish, and vegetable oil (canola oil in HND and olive oil in MD), but restrict the use of saturated fat and red and processed meat. The aim of this narrative review is to summarize the results of studies, which have investigated the associations or effects of HND on the markers of LGI. Altogether, only two publications of observational studies and eight publications of intervention trials were found through the literature search. Both observational studies reported an inverse association between the adherence to HND and concentration of high sensitivity C-reactive protein (hsCRP). A significant decrease in the concentration of hsCRP was reported in two out of four intervention studies measuring hsCRP. Single intervention studies reported the beneficial effects on interleukin 1Ra and Cathepsin S. Current evidence suggests the beneficial effects on LGI with HND, but more carefully controlled studies are needed to confirm the anti-inflammatory effects of the HND.
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Sivasinprasasn S, Wikan N, Tocharus J, Pantan R, Chaichompoo W, Suksamrarn A, Tocharus C. Synergistic effects of the capsaicinoid nonivamide and rosuvastatin on obesity‐related endothelial dysfunction in rat fed a high‐fat diet. Phytother Res 2019; 33:1815-1826. [DOI: 10.1002/ptr.6369] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 03/17/2019] [Accepted: 03/26/2019] [Indexed: 12/27/2022]
Affiliation(s)
| | - Naruemon Wikan
- Department of Anatomy, Faculty of MedicineChiang Mai University Chiang Mai Thailand
| | - Jiraporn Tocharus
- Department of Physiology, Faculty of MedicineChiang Mai University Chiang Mai Thailand
| | - Rungusa Pantan
- Department of Anatomy, Faculty of MedicineChiang Mai University Chiang Mai Thailand
| | - Waraluck Chaichompoo
- Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of ScienceRamkhamhaeng University Bangkok Thailand
| | - Apichart Suksamrarn
- Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of ScienceRamkhamhaeng University Bangkok Thailand
| | - Chainarong Tocharus
- Department of Anatomy, Faculty of MedicineChiang Mai University Chiang Mai Thailand
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Wang P, Wang SC, Yang H, Lv C, Jia S, Liu X, Wang X, Meng D, Qin D, Zhu H, Wang YF. Therapeutic Potential of Oxytocin in Atherosclerotic Cardiovascular Disease: Mechanisms and Signaling Pathways. Front Neurosci 2019; 13:454. [PMID: 31178679 PMCID: PMC6537480 DOI: 10.3389/fnins.2019.00454] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 04/23/2019] [Indexed: 12/12/2022] Open
Abstract
Coronary artery disease (CAD) is a major cardiovascular disease responsible for high morbidity and mortality worldwide. The major pathophysiological basis of CAD is atherosclerosis in association with varieties of immunometabolic disorders that can suppress oxytocin (OT) receptor (OTR) signaling in the cardiovascular system (CVS). By contrast, OT not only maintains cardiovascular integrity but also has the potential to suppress and even reverse atherosclerotic alterations and CAD. These protective effects of OT are associated with its protection of the heart and blood vessels from immunometabolic injuries and the resultant inflammation and apoptosis through both peripheral and central approaches. As a result, OT can decelerate the progression of atherosclerosis and facilitate the recovery of CVS from these injuries. At the cellular level, the protective effect of OT on CVS involves a broad array of OTR signaling events. These signals mainly belong to the reperfusion injury salvage kinase pathway that is composed of phosphatidylinositol 3-kinase-Akt-endothelial nitric oxide synthase cascades and extracellular signal-regulated protein kinase 1/2. Additionally, AMP-activated protein kinase, Ca2+/calmodulin-dependent protein kinase signaling and many others are also implicated in OTR signaling in the CVS protection. These signaling events interact coordinately at many levels to suppress the production of inflammatory cytokines and the activation of apoptotic pathways. A particular target of these signaling events is endoplasmic reticulum (ER) stress and mitochondrial oxidative stress that interact through mitochondria-associated ER membrane. In contrast to these protective effects and machineries, rare but serious cardiovascular disturbances were also reported in labor induction and animal studies including hypotension, reflexive tachycardia, coronary spasm or thrombosis and allergy. Here, we review our current understanding of the protective effect of OT against varieties of atherosclerotic etiologies as well as the approaches and underlying mechanisms of these effects. Moreover, potential cardiovascular disturbances following OT application are also discussed to avoid unwanted effects in clinical trials of OT usages.
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Affiliation(s)
- Ping Wang
- Department of Genetics, School of Basic Medical Sciences, Harbin Medical University, Harbin, China
| | - Stephani C Wang
- Department of Medicine, Albany Medical Center, Albany, NY, United States
| | - Haipeng Yang
- Department of Pediatrics, The Forth Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Chunmei Lv
- Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China
| | - Shuwei Jia
- Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China
| | - Xiaoyu Liu
- Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China
| | - Xiaoran Wang
- Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China
| | - Dexin Meng
- Department of Physiology, Jiamusi University, Jiamusi, China
| | - Danian Qin
- Department of Physiology, Shantou University of Medical College, Shantou, China
| | - Hui Zhu
- Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China
| | - Yu-Feng Wang
- Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China
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Virdis A, Masi S, Colucci R, Chiriacò M, Uliana M, Puxeddu I, Bernardini N, Blandizzi C, Taddei S. Microvascular Endothelial Dysfunction in Patients with Obesity. Curr Hypertens Rep 2019; 21:32. [DOI: 10.1007/s11906-019-0930-2] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Liu J, Shi YC, Lee DYW. Applications of Pueraria lobata in treating diabetics and reducing alcohol drinking. CHINESE HERBAL MEDICINES 2019; 11:141-149. [PMID: 32831815 PMCID: PMC7434045 DOI: 10.1016/j.chmed.2019.04.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Pueraria lobata is one of the most important medicinal herbs used traditionally in China. According to Shanghan Lun (Treatise on Exogenous Febrile Disease), it has been used traditionally to relieve body heat, eye soring, dry mouth, headache associated with high blood pressure, and stiff neck problems. Modern studies in the 1970s revealed that isoflavonoids extracted from P. lobata were the bioactive components of an herbal remedy namely Yufeng Ningxin Tablets for the treatment of patients after stroke. This article reviews recent application of P. lobota in the treatment of diabetics and in reducing alcohol drinking. In view of its low toxicity profile, P. lobota stands an excellent chance to be developed as a phytomedicine for treating human diseases.
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Affiliation(s)
- Jing Liu
- Bio-Organic and Natural Products Research Laboratory, Mailman Research Center, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA
| | | | - David Yue-Wei Lee
- Bio-Organic and Natural Products Research Laboratory, Mailman Research Center, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA
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Jha D, Mitra Mazumder P. High fat diet administration leads to the mitochondrial dysfunction and selectively alters the expression of class 1 GLUT protein in mice. Mol Biol Rep 2019; 46:1727-1736. [PMID: 30725350 DOI: 10.1007/s11033-019-04623-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Accepted: 01/18/2019] [Indexed: 01/07/2023]
Abstract
Metabolic syndrome is an agglomeration of disorders including obesity, diabetes and cardiovascular diseases and characterized as chronic mild inflammation which elevates the circulatory inflammatory markers. This could be due to mitochondrial dysfunction, oxidative stress and hypoxia as a consequence of high fat diet (HFD) intake. The present study focuses on the effects of HFD on lactate and mitochondrial metabolism as well as tissue dependent changes in glucose transporter (GLUT) expression in liver, skeletal muscles and adipose tissue of mouse. Lactate dehydrogenase (LDH) and mitochondrial dysfunction established the link between the occurrences of metabolic stress due to HFD. In this work, it was observed that chronic HFD administration aggravated the metabolic alterations by causing reduced ATP production, imbalanced oxidative stress and altered class 1 GLUTs expression. Chronic HFD significantly reduced (p < 0.001) the superoxide dismutase (SOD), catalase (CAT) activities alongside elevated liver injury markers AST and ALT. This in turn causes decreased ATP/ADP ratio, mitochondrial dysfunction and exacerbated LDH levels. This imbalance further led to altered GLUT expression in hepatic cells, adipose tissue and skeletal muscles. HFD significantly (p < 0.001) upregulated the GLUT 1 and 3 expressions while significant downregulated (p < 0.001) GLUT 2 and 4 expression in liver, skeletal muscles and white adipose tissue. These results revealed the link between class 1 GLUTs, mitochondrial dysfunction and HFD-induced metabolic disorder. It can be concluded that HFD impacts mitochondrial metabolism and reprograms tissue-dependent glucose transporter.
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Affiliation(s)
- Dhruv Jha
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, 835215, India.
| | - Papiya Mitra Mazumder
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, 835215, India
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Virdis A, Colucci R, Bernardini N, Blandizzi C, Taddei S, Masi S. Microvascular Endothelial Dysfunction in Human Obesity: Role of TNF-α. J Clin Endocrinol Metab 2019; 104:341-348. [PMID: 30165404 DOI: 10.1210/jc.2018-00512] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Accepted: 08/21/2018] [Indexed: 02/09/2023]
Abstract
CONTEXT Endothelium guarantees vascular homeostasis by the opposite action of substances by vasodilating/antithrombogenic and vasoconstricting/prothrombotic activities. Obesity is characterized by endothelial dysfunction associated with a condition of vascular low-grade inflammation. EVIDENCE ACQUISITION Analysis of available basic or clinical papers published in peer-reviewed international journals on microcirculation and obesity. EVIDENCE SYNTHESIS Vascular low-grade inflammation, which characterizes obesity, is secondary to abnormal production of proinflammatory cytokines, including TNF-α. TNF-α, generated either in small vessels or within the perivascular adipose tissue (PVAT) of patients with obesity, stimulates reactive oxygen species generation, mainly through NAD(P)H oxidase activation, which in turn reduces nitric oxide (NO) availability. These aspects are highlighted by the insulin resistance status and macronutrient intake that characterize the obesity condition. Oxidant excess has also been proposed as a mechanism whereby TNF-α interferes with the endothelin-1/NO system at the level of small vessels from patients with obesity. CONCLUSIONS In obesity, microvasculature from visceral fat is an important source of low-grade inflammation and oxidative stress that, together with the PVAT, directly contribute to vascular changes, favoring the development and acceleration of the vascular atherothrombotic process in this clinical condition.
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Affiliation(s)
- Agostino Virdis
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Rocchina Colucci
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | - Nunzia Bernardini
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Corrado Blandizzi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Stefano Taddei
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Stefano Masi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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Kir S, Ekiz K, Alacam H, Turkel R, Koroglu E, Altintop BL. THE ASSOCIATION BETWEEN PRO AND ANTI-INFLAMMATORY MARKERS WITH THE COMPONENTS OF METABOLIC SYNDROME. ACTA ENDOCRINOLOGICA-BUCHAREST 2019; 15:430-435. [PMID: 32377238 DOI: 10.4183/aeb.2019.430] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Objectives Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that is linked with increased circulating markers of oxidative stress and low-grade inflammation. The link between inflammation and MetS is not yet fully understood. We aim to evaluate the relationship between the levels of pro and anti-inflammatory markers such as apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B), interleukin (IL) 6, tumor necrosis factor alpha (TNF-α), fibrinogen and complement component 3 (C3) and adiponectin and MetS/MetS components. Methods This study was a case-control study conducted in an outpatient internal medicine clinic of the Ondokuz Mayıs University Internal Medicine Department. A total of 108 subjects (59 female, 49 male) who were not under any dietary restrictions and older than 17 years were selected and divided into two groups (54 with MetS and 54 healthy controls). Results Increased levels of IL-6, C3 and Apo-B/Apo-A1 ratios and decreased levels of Apo-A1 and TNF-α (except in patients with hypertriglyceridemia) were detected in the MetS group. Apo-A1 and TNF-α exhibited decreased levels, and IL-6, fibrinogen, C3 and Apo-B levels and Apo-B/Apo-A1 ratios increased as higher numbers of MetS criteria were met in the total study group. Conclusions We found that inflammatory marker levels were not affected by an increased number of MetS criteria met in the MetS group although these levels increased in the control group with higher numbers of MetS components. The presence of a high number of MetS components does not have an additive pro-inflammatory contribution for subjects already diagnosed with MetS.
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Affiliation(s)
- S Kir
- Ondokuz Mayis University, Faculty of Medicine, Department of Internal Medicine, Samsun, Turkey
| | - K Ekiz
- Ondokuz Mayis University, Faculty of Medicine, Department of Internal Medicine, Samsun, Turkey
| | - H Alacam
- Ondokuz Mayis University, Faculty of Medicine, Department of Biochemistry, Samsun, Turkey
| | - R Turkel
- Ondokuz Mayis University, Faculty of Medicine, Department of Internal Medicine, Samsun, Turkey
| | - E Koroglu
- Ondokuz Mayis University, Faculty of Medicine, Department of Internal Medicine, Samsun, Turkey
| | - B L Altintop
- Ondokuz Mayis University, Faculty of Medicine, Department of Internal Medicine, Samsun, Turkey
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Alman AC, Talton JW, Wadwa RP, Urbina EM, Dolan LM, Hamman RF, D'Agostino RB, Marcovina SM, Dabelea DM. Inflammation, adiposity, and progression of arterial stiffness in adolescents with type 1 diabetes: The SEARCH CVD Study. J Diabetes Complications 2018; 32:995-999. [PMID: 30209019 PMCID: PMC6174105 DOI: 10.1016/j.jdiacomp.2018.08.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Revised: 12/28/2017] [Accepted: 08/06/2018] [Indexed: 11/30/2022]
Abstract
AIMS We examined the association between inflammation and progression of arterial stiffness in a population of youth with type 1 diabetes (T1D). METHODS A total of 287 youth with T1D (median age 13 years) from SEARCH CVD, an ancillary study to the SEARCH for Diabetes in Youth, were included. Markers of inflammation (CRP, IL-6, fibrinogen, leptin, and adiponectin) and measures of pulse wave velocity (PWV) of the arm (PWV-R), trunk (PWV-T), and lower extremity (PWV-LE) were measured at baseline. Measures of PWV were repeated approximately five years later. RESULTS PWV-R (0.50 m/s), PWV-T (0.65 m/s), and PWV-LE (1.0 m/s) significantly increased over the follow-up (p < 0.001 for each). A significant interaction was found between waist circumference and fibrinogen (p = 0.036) on the progression of PWV-T, suggesting that fibrinogen is more strongly associated with PWV progression in lean participants. CONCLUSIONS Improved understanding of adiposity, inflammation, and functional changes in the vascular system in patients with T1D is crucial.
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Affiliation(s)
- Amy C Alman
- Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, USA.
| | - Jennifer W Talton
- Department of Biostatistical Sciences, Wake Forest School of Medicine, USA
| | - R Paul Wadwa
- Barbara Davis Center, University of Colorado Denver, USA
| | - Elaine M Urbina
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, USA
| | - Lawrence M Dolan
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, USA
| | - Richard F Hamman
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, USA
| | - Ralph B D'Agostino
- Department of Biostatistical Sciences, Wake Forest School of Medicine, USA
| | - Santica M Marcovina
- Department of Metabolism, Endocrinology and Nutrition, University of Washington, USA
| | - Dana M Dabelea
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, USA
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Alman AC, Smith SR, Eckel RH, Hokanson JE, Burkhardt BR, Sudini PR, Wu Y, Schauer IE, Pereira RI, Snell-Bergeon JK. The ratio of pericardial to subcutaneous adipose tissues is associated with insulin resistance. Obesity (Silver Spring) 2017; 25:1284-1291. [PMID: 28558132 PMCID: PMC5488713 DOI: 10.1002/oby.21875] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2017] [Revised: 03/17/2017] [Accepted: 04/10/2017] [Indexed: 11/12/2022]
Abstract
OBJECTIVE To examine the association between pericardial adipose tissue (PAT) and the ratio of PAT to subcutaneous adipose tissue (SAT) with insulin resistance in adults with and without type 1 diabetes (T1D). METHODS Data for this report came from a substudy of the Coronary Artery Calcification in Type 1 Diabetes cohort (n = 83; 38 with T1D, 45 without T1D). Insulin resistance was measured by hyperinsulinemic-euglycemic clamp. Abdominal computed tomography (CT) was used to measure visceral adipose tissue (VAT) and SAT. PAT was measured from CT scans of the heart. RESULTS PAT and the ratio of PAT to SAT was higher in males compared to females. After adjustment for demographics, diabetes, blood pressure and lipid factors, BMI, VAT, and log PAT/SAT ratio, log PAT was positively associated with the glucose infusion rate (GIR) in females only (β = 3.36 ± 1.96, P = 0.097, P for sex interaction = 0.055). Conversely, the log PAT/SAT ratio was significantly associated with decreased GIR in both males and females (β = -2.08 ± 1.03, P = 0.047, P for sex interaction = 0.768). CONCLUSIONS A significant association between the PAT/SAT ratio and insulin resistance was found, independent of BMI, VAT, and PAT. These results highlight the importance of considering fat distribution independent of volume.
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Affiliation(s)
- Amy C. Alman
- Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, FL USA
| | - Steven R. Smith
- Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL USA
| | - Robert H. Eckel
- Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Colorado Denver, Aurora, CO USA
| | - John E. Hokanson
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO USA
| | - Brant R. Burkhardt
- Department of Cell Biology, Microbiology and Molecular Biology, College of Liberal Arts and Sciences, University of South Florida, Tampa, FL USA
| | - Preethi R. Sudini
- Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, FL USA
| | - Yougui Wu
- Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, FL USA
| | - Irene E. Schauer
- Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Colorado Denver, Aurora, CO USA
- Denver VA Medical Center, Denver, CO
| | - Rocio I. Pereira
- Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Colorado Denver, Aurora, CO USA
- Denver Health Medical Center, Denver, CO
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Hodkinson JP. Considerations for dosing immunoglobulin in obese patients. Clin Exp Immunol 2017; 188:353-362. [PMID: 28263379 PMCID: PMC5422718 DOI: 10.1111/cei.12955] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/01/2017] [Indexed: 12/17/2022] Open
Abstract
Obesity is a very common condition; however, the effect of excess body weight on the appropriate dose of immunoglobulin has not been defined empirically. The proposed pharmacokinetic differences between lean and obese patients and the opportunity to reduce costs has led to the proposition that obese patients should receive proportionally lower doses of immunoglobulin once a certain threshold is reached. Here the theoretical factors which could affect dosing in obese patients are considered alongside the available empirical evidence. The available evidence indicates that obesity may affect the pharmacokinetics of immunoglobulin; however, the effect is likely to be too small to have a clinically important effect on dosing. Wide interpatient individuality and highly variable clinical need mean that obesity should not play a major factor in dosing considerations. However, patients who are obese are more likely to have multiple cardiovascular risk factors and their weight indicates a large dose. This puts these patients at a higher risk of adverse reactions, and therefore caution is advised.
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Affiliation(s)
- J P Hodkinson
- Corporate Medical Affairs, Biotest AG, Dreieich, Germany
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Das A. Depression, Inflammation, and Physiological Risk in Late Life: A National Longitudinal Study. BIODEMOGRAPHY AND SOCIAL BIOLOGY 2017; 63:131-147. [PMID: 28521620 DOI: 10.1080/19485565.2017.1308245] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
This nationally representative study queried effects of community dwelling older adults' depression and inflammation at baseline on over-time changes in surrogate markers of their cardiometabolic risk. Data were from the 2005-2006 and 2010-2011 waves of the U.S. National Social Life, Health, and Aging Project. Inflammation was indicated by C-reactive protein and depression by the CES-D scale. Cardiometabolic markers included hemoglobin A1c and systolic BP. Lagged dependent variable models were used to examine effects. In none of the models did Wave 1 depression predict residual change in cardiometabolic states (i.e., Wave 2 values net of Wave 1). In contrast, men's baseline C-reactive protein predicted their Wave 2 hemoglobin A1c (Coeff. = 0.02, p < .05) as well as their systolic BP (Coeff. = 3.22, p < .05). No such effects were found among women. Contrary to a growing clinical literature, depression may not increase cardiometabolic risk among older adults on average. Moderators that may interact with depression to yield such effects in delimited samples remain to be identified. Inflammation, in contrast, does seem linked to increase in physiological risk-but only among men, not women. Clinical research is needed to identify biological factors responsible for this sex difference.
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Affiliation(s)
- Aniruddha Das
- a Department of Sociology , McGill University , Montreal , Quebec , Canada
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Does apical periodontitis have systemic consequences? The need for well-planned and carefully conducted clinical studies. Br Dent J 2016; 218:513-6. [PMID: 25952428 DOI: 10.1038/sj.bdj.2015.340] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/08/2015] [Indexed: 12/18/2022]
Abstract
Apical periodontitis, infection of the root canal system, may have systemic consequences. This proposal has been brought forward many times in dentistry literature but the general consensus is that there is no scientific basis for an association between endodontic infections and general health. This opinion paper argues that, in order to obtain such a scientific basis, or to rule out the issue all together, we need carefully designed longitudinal challenge model (that is, intervention) studies in which we follow specific biomarkers of inflammation. These biomarkers can be those that are currently being substantiated in chronic inflammation and low-grade inflammation studies in medicine and nutritional science, where the presence of these inflammatory disorders is linked to systemic outcomes. A list of suggested biomarkers has been included.
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Paniagua JA. Nutrition, insulin resistance and dysfunctional adipose tissue determine the different components of metabolic syndrome. World J Diabetes 2016; 7:483-514. [PMID: 27895819 PMCID: PMC5107710 DOI: 10.4239/wjd.v7.i19.483] [Citation(s) in RCA: 113] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Revised: 08/16/2016] [Accepted: 09/07/2016] [Indexed: 02/05/2023] Open
Abstract
Obesity is an excessive accumulation of body fat that may be harmful to health. Today, obesity is a major public health problem, affecting in greater or lesser proportion all demographic groups. Obesity is estimated by body mass index (BMI) in a clinical setting, but BMI reports neither body composition nor the location of excess body fat. Deaths from cardiovascular diseases, cancer and diabetes accounted for approximately 65% of all deaths, and adiposity and mainly abdominal adiposity are associated with all these disorders. Adipose tissue could expand to inflexibility levels. Then, adiposity is associated with a state of low-grade chronic inflammation, with increased tumor necrosis factor-α and interleukin-6 release, which interfere with adipose cell differentiation, and the action pattern of adiponectin and leptin until the adipose tissue begins to be dysfunctional. In this state the subject presents insulin resistance and hyperinsulinemia, probably the first step of a dysfunctional metabolic system. Subsequent to central obesity, insulin resistance, hyperglycemia, hypertriglyceridemia, hypoalphalipoproteinemia, hypertension and fatty liver are grouped in the so-called metabolic syndrome (MetS). In subjects with MetS an energy balance is critical to maintain a healthy body weight, mainly limiting the intake of high energy density foods (fat). However, high-carbohydrate rich (CHO) diets increase postprandial peaks of insulin and glucose. Triglyceride-rich lipoproteins are also increased, which interferes with reverse cholesterol transport lowering high-density lipoprotein cholesterol. In addition, CHO-rich diets could move fat from peripheral to central deposits and reduce adiponectin activity in peripheral adipose tissue. All these are improved with monounsaturated fatty acid-rich diets. Lastly, increased portions of ω-3 and ω-6 fatty acids also decrease triglyceride levels, and complement the healthy diet that is recommended in patients with MetS.
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Autieri MV. Adipose inflammation at the heart of vascular disease. Clin Sci (Lond) 2016; 130:2101-2104. [PMID: 27729474 PMCID: PMC6339250 DOI: 10.1042/cs20160628] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2016] [Accepted: 09/09/2016] [Indexed: 01/13/2023]
Abstract
Visceral adipose tissue is a primary site of chronic inflammation in obesity and may contribute to systemic inflammation and development of atherosclerotic vascular disease. Few studies identify molecular mechanisms and secretory pathways which mediate this process. In this edition of Clinical Science, Kwok et al. utilize a transgenic mouse in which dominant-negative c-Jun NH2 terminal kinase (dnJNK) expression is restricted to adipose tissue to implicate JNK-driven expression of adipocyte fatty acid binding protein (A-FABP) in visceral adipose tissue as a key secretory pathway to exacerbate development of atherosclerosis in ApoE-/- mice. They further demonstrate that ApoE-/- mice transplanted with visceral adipose tissue in which JNK has been inactivated display less systemic inflammation and develop significantly less atherosclerosis compared with control mice. Together, the findings of the present study reinforce our understanding of visceral adipose tissue as a secretory organ and the importance of the JNK/A-FABP pathway in mediating adipose vascular cross-talk and exacerbation of atherosclerosis.
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Affiliation(s)
- Michael V Autieri
- Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, U.S.A.
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Das A. Psychosocial distress and inflammation: Which way does causality flow? Soc Sci Med 2016; 170:1-8. [PMID: 27728857 DOI: 10.1016/j.socscimed.2016.10.001] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2016] [Revised: 09/12/2016] [Accepted: 10/02/2016] [Indexed: 12/15/2022]
Abstract
OBJECTIVES This study queried causal direction in linkages of inflammation with psychosocial distress. METHODS Data were from the 2005-2006 and 2010-2011 waves of the U.S. National Social Life, Health, and Aging Project. Inflammation was indicated by C-reactive protein, and distress by depression, anxiety, as well as stress. Autoregressive cross-lagged panel models were used to examine causal direction. RESULTS Rather than being an outcome of psychosocial distress, inflammation was a predictor of it. Linkages were gender differentiated, with inflammation seeming to induce depression among men but stress among women. DISCUSSION Contrary to previous literature, inflammation may not be a mechanism through which psychosocial distress gets "under the skin" to cause cardiovascular and metabolic issues. Rather, it may be a node through which social pathologies and life events influence both mental health and physiological problems.
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Affiliation(s)
- Aniruddha Das
- Department of Sociology, McGill University, Room 712, Leacock Building, 855 Sherbrooke Street West, Montreal, Quebec H3A 2T7, Canada.
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Zhi G, Xin W, Ying W, Guohong X, Shuying L. "Obesity Paradox" in Acute Respiratory Distress Syndrome: Asystematic Review and Meta-Analysis. PLoS One 2016; 11:e0163677. [PMID: 27684705 PMCID: PMC5042414 DOI: 10.1371/journal.pone.0163677] [Citation(s) in RCA: 124] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Accepted: 09/12/2016] [Indexed: 01/08/2023] Open
Abstract
Background It is unclear whether an “obesity paradox” exists in the respiratory system, especially in acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Previous studies have postulated a causal relation between obesity and ARDS/ALI but have lacked power to form a definitive conclusion. Objective To investigate the relationships between obesity, ARDS/ALIrisk, and mortality. Methods A systematic search current to April 2016 was performed in Pubmed, EMBASE, Medline, Cochrane databases to find relevant studies. All studies that estimate the effect of obesity in the morbidity and mortality of ARDS/ALI were included. Results A total of 24 studies including 9,187,248 subjects were analyzed. The combined results from 16 studies that examined the effect of obesity in morbidity of ARDS/ALI showed an89% increase in odds ratio(pooled odds ratios (OR) 1.89, 95% confidence intervals (CI) 1.45 to 2.47). In subgroup analysis, compared to normal weight, obesity was associated with an increased risk of ARDS/ALI (OR1.57, 95% CI 1.30–1.90 for obese (BMI30-39.9kg/m2); OR1.75, 95% CI 1.42–2.15 for obese(BMI≥30kg/m2); OR1.67, 95% CI 1.04–2.68 for morbid obese(BMI≥40kg/m2)). The combined results from 9 studies that examined the effect of obesity in mortality of ARDS/ALI had a pooled odds ratio(pooled OR 0.63, 95% CI 0.41 to 0.98). Inversely, obesity was significantly associated with reduced risk of ARDS/ALI mortality(OR0.88, 95% CI 0.78–1.00 for overweight(BMI≤18.5m2); OR0.74, 95% CI 0.64–0.84 for obese (BMI30-39.9kg/m2);OR0.84, 95% CI 0.75–0.94 for 60days mortality; OR0.38, 95% CI 0.22–0.66 for 90days mortality). Conclusions Our data identify obesity as an important risk factor for the development of ARDS/ALI; however, ARDS/ALI outcomes are improved in this population when compared to individuals with a normal body mass index. This meta-analysis results supported ‘‘obesity paradox” in ARDS/ALI.
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Affiliation(s)
- Guo Zhi
- Department of Pulmonary Diseases,Jinan Military General Hospital,Jinan, 250031, China
| | - Wang Xin
- Department of Pulmonary Diseases,Jinan Military General Hospital,Jinan, 250031, China
| | - Wang Ying
- Department of Pulmonary Diseases,Jinan Military General Hospital,Jinan, 250031, China
| | - Xing Guohong
- Department of Pulmonary Diseases,Jinan Military General Hospital,Jinan, 250031, China
| | - Liu Shuying
- Department of Pulmonary Diseases,Jinan Military General Hospital,Jinan, 250031, China
- * E-mail:
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Polus A, Zapala B, Razny U, Gielicz A, Kiec-Wilk B, Malczewska-Malec M, Sanak M, Childs CE, Calder PC, Dembinska-Kiec A. Omega-3 fatty acid supplementation influences the whole blood transcriptome in women with obesity, associated with pro-resolving lipid mediator production. Biochim Biophys Acta Mol Cell Biol Lipids 2016; 1861:1746-1755. [PMID: 27531277 DOI: 10.1016/j.bbalip.2016.08.005] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Revised: 08/07/2016] [Accepted: 08/10/2016] [Indexed: 12/14/2022]
Abstract
The n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may reduce low-grade inflammation associated with obesity. The relationship between therapeutic response to n-3 PUFAs and modification of the transcriptome in obesity or metabolic syndrome remains to be explored. Blood samples were obtained from women with obesity before and after three-months supplementation with a moderate dose of n-3 PUFAs (1.8g EPA+DHA per day) or from controls. n-3 PUFAs (GC) and plasma concentrations of lipoxins, resolvins, protectin X (GC-MS/MS) and inflammatory markers (ELISA) were measured. Whole blood transcriptome was assayed using microarray. Women supplemented with n-3 PUFAs for 3months had significantly higher levels of EPA and DHA in plasma phosphatidylcholine. n-3 PUFA supplementation, in contrast to placebo, significantly decreased the concentrations of several inflammatory markers (SELE, MCP-1, sVCAM-1, sPECAM-1, and hsCRP), fasting triglycerides and insulin and increased the concentrations of pro-resolving DHA derivatives in plasma. The microarray data demonstrated effects of n-3 PUFAs on PPAR-α, NRF2 and NF-κB target genes. N-3 PUFAs increased DHA-derived pro-resolving mediators in women with obesity. Elevated resolvins and up-regulation of the resolvin receptor occurred in parallel with activation of PPAR-α target genes related to lipid metabolism and of NRF2 up-regulated antioxidant enzymes.
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Affiliation(s)
- Anna Polus
- Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian University, Krakow, Poland.
| | - Barbara Zapala
- Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian University, Krakow, Poland
| | - Urszula Razny
- Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian University, Krakow, Poland
| | - Anna Gielicz
- Department of Molecular Biology and Clinical Genetics Laboratory, Collegium Medicum, Jagiellonian University, Krakow, Poland
| | - Beata Kiec-Wilk
- Department of Metabolic Disorders, Collegium Medicum, Jagiellonian University, Krakow, Poland
| | | | - Marek Sanak
- Department of Molecular Biology and Clinical Genetics Laboratory, Collegium Medicum, Jagiellonian University, Krakow, Poland
| | - Caroline E Childs
- Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
| | - Philip C Calder
- Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, University of Southampton, Southampton, United Kingdom
| | - Aldona Dembinska-Kiec
- Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian University, Krakow, Poland
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Fowke JH, Koyama T, Fadare O, Clark PE. Does Inflammation Mediate the Obesity and BPH Relationship? An Epidemiologic Analysis of Body Composition and Inflammatory Markers in Blood, Urine, and Prostate Tissue, and the Relationship with Prostate Enlargement and Lower Urinary Tract Symptoms. PLoS One 2016; 11:e0156918. [PMID: 27336586 PMCID: PMC4918934 DOI: 10.1371/journal.pone.0156918] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2016] [Accepted: 05/20/2016] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND BPH is a common disease associated with age and obesity. However, the biological pathways between obesity and BPH are unknown. Our objective was to investigate biomarkers of systemic and prostate tissue inflammation as potential mediators of the obesity and BPH association. METHODS Participants included 191 men without prostate cancer at prostate biopsy. Trained staff measured weight, height, waist and hip circumferences, and body composition by bioelectric impedance analysis. Systemic inflammation was estimated by serum IL-6, IL-1β, IL-8, and TNF-α; and by urinary prostaglandin E2 metabolite (PGE-M), F2-isoprostane (F2iP), and F2-isoprostane metabolite (F2iP-M) levels. Prostate tissue was scored for grade, aggressiveness, extent, and location of inflammatory regions, and also stained for CD3 and CD20 positive lymphocytes. Analyses investigated the association between multiple body composition scales, systemic inflammation, and prostate tissue inflammation against BPH outcomes, including prostate size at ultrasound and LUTS severity by the AUA-symptom index (AUA-SI). RESULTS Prostate size was significantly associated with all obesity measures. For example, prostate volume was 5.5 to 9.0 mls larger comparing men in the 25th vs. 75th percentile of % body fat, fat mass (kg) or lean mass (kg). However, prostate size was not associated with proinflammatory cytokines, PGE-M, F2iP, F2iP-M, prostate tissue inflammation scores or immune cell infiltration. In contrast, the severity of prostate tissue inflammation was significantly associated with LUTS, such that there was a 7 point difference in AUA-SI between men with mild vs. severe inflammation (p = 0.004). Additionally, men with a greater waist-hip ratio (WHR) were significantly more likely to have severe prostate tissue inflammation (p = 0.02), and a high WHR was significantly associated with moderate/severe LUTS (OR = 2.56, p = 0.03) among those participants with prostate tissue inflammation. CONCLUSION The WHR, an estimate of centralized obesity, was associated with the severity of inflammatory regions in prostate tissue and with LUTS severity among men with inflammation. Our results suggest centralized obesity advances prostate tissue inflammation to increase LUTS severity. Clinically targeting centralized fat deposition may reduce LUTS severity. Mechanistically, the lack of a clear relationship between systemic inflammatory or oxidative stress markers in blood or urine with prostate size or LUTS suggests pathways other than systemic inflammatory signaling may link body adiposity to BPH outcomes.
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Affiliation(s)
- Jay H. Fowke
- Departments of Medicine and Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, United States of America
- * E-mail:
| | - Tatsuki Koyama
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, United States of America
| | - Oluwole Fadare
- Department of Pathology, University of California San Diego, San Diego, CA, United States of America
| | - Peter E. Clark
- Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, United States of America
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