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Li C, Zeng L, Li M, Deng K, Zhou D, Liang R, Zhang X, Hu Z, Luo A, Chen C, Chen Q, Wei W, Li W, Hu Z. New sagittal abdominal diameter and transverse abdominal diameter based equations to estimate visceral fat area in type 2 diabetes patients. BMC Public Health 2024; 24:1364. [PMID: 38773444 PMCID: PMC11106903 DOI: 10.1186/s12889-024-18659-8] [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: 11/02/2023] [Accepted: 04/18/2024] [Indexed: 05/23/2024] Open
Abstract
OBJECTIVE Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) are considered gold standards for measuring visceral fat area (VFA). However, their relatively high prices and potential radiation exposure limit their widespread use in clinical practice and everyday life. Therefore, our study aims to develop a VFA estimated equation based on sagittal abdominal diameter (SAD) and transverse abdominal diameter (TAD) using anthropometric indexes. To the best of our knowledge, there have been limited studies investigating this aspect thus far. METHODS This study was designed as a cross-sectional, retrospective cohort survey. A total of 288 patients (167 males and 121 females) aged 18-80 with type 2 diabetes (T2D) were consecutively collected from a multicenter hospital, and VFA was measured by CT. Subsequently, variables highly correlated with VFA were screened through general linear correlation analysis. A stepwise regression analysis was then conducted to develop a VFA estimated equation. Discrepancies between the estimated and actual VFA values were assessed using the Bland-Altman method to validate the accuracy of the equation. RESULTS In the female T2D population, triglyceride (TG), SAD, TAD were found to be independently correlated with VFA; in the male T2D population, BMI, TG, SAD and TAD showed independent correlations with VFA. Among these variables, SAD exhibited the strongest correlation with VFA (r = 0.83 for females, r = 0.88 for males), followed by TAD (r = 0.69 for females, r = 0.79 for males). Based on these findings, a VFA estimated equation was developed for the T2D population: VFA (male) =-364.16 + 15.36*SAD + 0.77*TG + 9.41*TAD - 5.00*BMI (R2 = 0.75, adjusted R2 = 0.74); VFA(female)=-170.87 + 9.72*SAD-24.29*(TG^-1) + 3.93*TAD (R2 = 0.69, adjusted R2 = 0.68). Both models demonstrated a good fit. The Bland-Altman plot indicated a strong agreement between the actual VFA values and the estimated values, the mean differences were close to 0, and the majority of differences fell within the 95% confidence interval. CONCLUSIONS In the T2D population, a VFA estimated equation is developed by incorporating SAD and TAD along with other measurement indices. This equation demonstrates a favorable estimated performance, suggesting to the development of novel and practical VFA estimation models in the future study.
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Affiliation(s)
- Chao Li
- Guangdong Medical University, Zhanjiang, 524001, China
| | - Liankun Zeng
- Department of Endocrinology, the Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 511300, China
| | - Miaosheng Li
- Department of Joint surgery, Affiliated Southwest Hospital of Youjiang Medical University for Nationalities, Baise, 533099, China
- Baise People's Hospital, Baise, 533099, China
| | - Kang Deng
- Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524002, China
| | - Die Zhou
- Department of Clinical Laboratory, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510220, China
| | - Rutao Liang
- Guangdong Medical University, Zhanjiang, 524001, China
| | - Xiaoshu Zhang
- Department of Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510220, China
| | - Zhihui Hu
- Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524002, China
| | - Ai Luo
- Department of Endocrinology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510220, China
| | - Chunling Chen
- Guangdong Medical University, Zhanjiang, 524001, China
| | - Qi Chen
- Guangdong Medical University, Zhanjiang, 524001, China
| | - Wenlong Wei
- Guangzhou Red Cross Hospital(Guangzhou Red Cross Hospital of Jinan University), Guangzhou, 510240, China
| | - Wangen Li
- Department of Endocrinology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510220, China.
- Guangzhou Medical University, Guangzhou, 510220, China.
| | - Zhuoqing Hu
- Department of Endocrinology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510220, China.
- Guangzhou Medical University, Guangzhou, 510220, China.
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Xu M, Wang W, Cheng J, Qu H, Xu M, Wang L. Effects of mitochondrial dysfunction on cellular function: Role in atherosclerosis. Biomed Pharmacother 2024; 174:116587. [PMID: 38636397 DOI: 10.1016/j.biopha.2024.116587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 04/02/2024] [Accepted: 04/10/2024] [Indexed: 04/20/2024] Open
Abstract
Atherosclerosis, an immunoinflammatory disease of medium and large arteries, is associated with life-threatening clinical events, such as acute coronary syndromes and stroke. Chronic inflammation and impaired lipoprotein metabolism are considered to be among the leading causes of atherosclerosis, while numerous risk factors, including arterial hypertension, diabetes mellitus, obesity, and aging, can contribute to the development of the disease. In recent years, emerging evidence has underlined the key role of mitochondrial dysfunction in the pathogenesis of atherosclerosis. Mitochondrial dysfunction is believed to result in an increase in reactive oxygen species, leading to oxidative stress, chronic inflammation, and intracellular lipid deposition, all of which can contribute to the pathogenesis of atherosclerosis. Critical cells, including endothelial cells, vascular smooth muscle cells, and macrophages, play an important role in atherosclerosis. Mitochondrial function is also involved in maintaining the normal function of these cells. To better understand the relationship between mitochondrial dysfunction and atherosclerosis, this review summarizes the findings of recent studies and discusses the role of mitochondrial dysfunction in the risk factors and critical cells of atherosclerosis. FACTS: OPEN QUESTIONS.
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Affiliation(s)
- Minwen Xu
- Clinical Skills Center, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China
| | - Wenjun Wang
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
| | - Jingpei Cheng
- Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou 341000, China; Basic Medical College, Gannan Medical University, Ganzhou 341000, China
| | - Hongen Qu
- Gannan Normal University, Ganzhou 341000, China.
| | - Minjuan Xu
- Department of Obstetrics and Gynecology, Ganzhou People's Hospital, Ganzhou 341000, China.
| | - Liefeng Wang
- Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou 341000, China; Basic Medical College, Gannan Medical University, Ganzhou 341000, China.
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Luo J, Alkhalidy H, Jia Z, Liu D. Sulforaphane Ameliorates High-Fat-Diet-Induced Metabolic Abnormalities in Young and Middle-Aged Obese Male Mice. Foods 2024; 13:1055. [PMID: 38611359 PMCID: PMC11012181 DOI: 10.3390/foods13071055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 03/23/2024] [Accepted: 03/26/2024] [Indexed: 04/14/2024] Open
Abstract
Type 2 diabetes (T2D) is still a fast-growing health problem globally. It is evident that chronic insulin resistance (IR) and progressive loss of β-cell mass and function are key features of T2D etiology. Obesity is a leading pathogenic factor for developing IR. The aim of the present study was to determine whether sulforaphane (SFN), a natural compound derived from cruciferous vegetables, can prevent (prevention approach) or treat (treatment approach) obesity and IR in mouse models. We show that dietary intake of SFN (0.5 g/kg of HFD) for 20 weeks suppressed high-fat diet (HFD)-induced fat accumulation by 6.04% and improved insulin sensitivity by 23.66% in young male mice. Similarly, dietary provision of SFN (0.25 g/kg) significantly improved blood lipid profile, glucose tolerance, and insulin sensitivity of the middle-aged male mice while it had little effects on body composition as compared with the HFD group. In the treatment study, oral administration of SFN (40 mg/kg) induced weight loss and improved insulin sensitivity and plasma lipid profile in the diet-induced-obesity (DIO) male mice. In all three studies, the metabolic effects of SFN administration were not associated with changes in food intake. In vitro, SFN increased glucose uptake in C2C12 myotubes and increased fatty acid and pyruvate oxidation in primary human skeletal muscle cells. Our results suggest that SFN may be a naturally occurring insulin-sensitizing agent that is capable of improving the metabolic processes in HFD-induced obesity and IR and thereby may be a promising compound for T2D prevention.
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Affiliation(s)
- Jing Luo
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China;
- Department of Human Nutrition, Foods, and Exercise, College of Agricultural and Life Sciences, Virginia Tech, Blacksburg, VA 24060, USA;
| | - Hana Alkhalidy
- Department of Human Nutrition, Foods, and Exercise, College of Agricultural and Life Sciences, Virginia Tech, Blacksburg, VA 24060, USA;
- Department of Nutrition and Food Technology, Faculty of Agriculture, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Zhenquan Jia
- Department of Biology, University of North Carolina at Greensboro, Greensboro, NC 27412, USA;
| | - Dongmin Liu
- Department of Human Nutrition, Foods, and Exercise, College of Agricultural and Life Sciences, Virginia Tech, Blacksburg, VA 24060, USA;
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Balan AI, Halațiu VB, Scridon A. Oxidative Stress, Inflammation, and Mitochondrial Dysfunction: A Link between Obesity and Atrial Fibrillation. Antioxidants (Basel) 2024; 13:117. [PMID: 38247541 PMCID: PMC10812976 DOI: 10.3390/antiox13010117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 01/11/2024] [Accepted: 01/16/2024] [Indexed: 01/23/2024] Open
Abstract
The adipose tissue has long been thought to represent a passive source of triglycerides and fatty acids. However, extensive data have demonstrated that the adipose tissue is also a major endocrine organ that directly or indirectly affects the physiological functions of almost all cell types. Obesity is recognized as a risk factor for multiple systemic conditions, including metabolic syndrome, type 2 diabetes mellitus, sleep apnea, cardiovascular disorders, and many others. Obesity-related changes in the adipose tissue induce functional and structural changes in cardiac myocytes, promoting a wide range of cardiovascular disorders, including atrial fibrillation (AF). Due to the wealth of epidemiologic data linking AF to obesity, the mechanisms underlying AF occurrence in obese patients are an area of rich ongoing investigation. However, progress has been somewhat slowed by the complex phenotypes of both obesity and AF. The triad inflammation, oxidative stress, and mitochondrial dysfunction are critical for AF pathogenesis in the setting of obesity via multiple structural and functional proarrhythmic changes at the level of the atria. The aim of this paper is to provide a comprehensive view of the close relationship between obesity-induced oxidative stress, inflammation, and mitochondrial dysfunction and the pathogenesis of AF. The clinical implications of these mechanistic insights are also discussed.
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Affiliation(s)
- Alkora Ioana Balan
- Center for Advanced Medical and Pharmaceutical Research, University of Medicine, Pharmacy, Science and Technology “George Emil Palade” of Târgu Mureș, 540142 Târgu Mureș, Romania;
| | - Vasile Bogdan Halațiu
- Physiology Department, University of Medicine, Pharmacy, Science and Technology “George Emil Palade” of Târgu Mureș, 540142 Târgu Mureș, Romania;
| | - Alina Scridon
- Center for Advanced Medical and Pharmaceutical Research, University of Medicine, Pharmacy, Science and Technology “George Emil Palade” of Târgu Mureș, 540142 Târgu Mureș, Romania;
- Physiology Department, University of Medicine, Pharmacy, Science and Technology “George Emil Palade” of Târgu Mureș, 540142 Târgu Mureș, Romania;
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Kueck PJ, Morris JK, Stanford JA. Current Perspectives: Obesity and Neurodegeneration - Links and Risks. Degener Neurol Neuromuscul Dis 2023; 13:111-129. [PMID: 38196559 PMCID: PMC10774290 DOI: 10.2147/dnnd.s388579] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 12/21/2023] [Indexed: 01/11/2024] Open
Abstract
Obesity is increasing in prevalence across all age groups. Long-term obesity can lead to the development of metabolic and cardiovascular diseases through its effects on adipose, skeletal muscle, and liver tissue. Pathological mechanisms associated with obesity include immune response and inflammation as well as oxidative stress and consequent endothelial and mitochondrial dysfunction. Recent evidence links obesity to diminished brain health and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Both AD and PD are associated with insulin resistance, an underlying syndrome of obesity. Despite these links, causative mechanism(s) resulting in neurodegenerative disease remain unclear. This review discusses relationships between obesity, AD, and PD, including clinical and preclinical findings. The review then briefly explores nonpharmacological directions for intervention.
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Affiliation(s)
- Paul J Kueck
- Department of Neurology, University of Kansas Medical Center, Kansas City, KS, 66160, USA
- Department of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, 66160, USA
| | - Jill K Morris
- Department of Neurology, University of Kansas Medical Center, Kansas City, KS, 66160, USA
- Department of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, 66160, USA
- University of Kansas Alzheimer’s Disease Research Center, University of Kansas Medical Center, Kansas City, KS, 66160, USA
| | - John A Stanford
- University of Kansas Alzheimer’s Disease Research Center, University of Kansas Medical Center, Kansas City, KS, 66160, USA
- Landon Center on Aging, University of Kansas Medical Center, Kansas City, KS, 66160, USA
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Monteiro-Alfredo T, Macedo MLR, de Picoli Souza K, Matafome P. New Therapeutic Strategies for Obesity and Its Metabolic Sequelae: Brazilian Cerrado as a Unique Biome. Int J Mol Sci 2023; 24:15588. [PMID: 37958572 PMCID: PMC10648839 DOI: 10.3390/ijms242115588] [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: 08/31/2023] [Revised: 10/21/2023] [Accepted: 10/23/2023] [Indexed: 11/15/2023] Open
Abstract
Brazil has several important biomes holding impressive fauna and flora biodiversity. Cerrado being one of the richest ones and a significant area in the search for new plant-based products, such as foods, cosmetics, and medicines. The therapeutic potential of Cerrado plants has been described by several studies associating ethnopharmacological knowledge with phytochemical compounds and therapeutic effects. Based on this wide range of options, the Brazilian population has been using these medicinal plants (MP) for centuries for the treatment of various health conditions. Among these, we highlight metabolic diseases, namely obesity and its metabolic alterations from metabolic syndrome to later stages such as type 2 diabetes (T2D). Several studies have shown that adipose tissue (AT) dysfunction leads to proinflammatory cytokine secretion and impaired free fatty acid (FFA) oxidation and oxidative status, creating the basis for insulin resistance and glucose dysmetabolism. In this scenario, the great Brazilian biodiversity and a wide variety of phytochemical compounds make it an important candidate for the identification of pharmacological strategies for the treatment of these conditions. This review aimed to analyze and summarize the current literature on plants from the Brazilian Cerrado that have therapeutic activity against obesity and its metabolic conditions, reducing inflammation and oxidative stress.
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Affiliation(s)
- Tamaeh Monteiro-Alfredo
- Coimbra Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal;
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal
- Clinical Academic Center of Coimbra, 3000-075 Coimbra, Portugal
- Research Group on Biotechnology and Bioprospection Applied to Metabolism and Cancer (GEBBAM), Federal University of Grande Dourados, Dourados 79804-970, MS, Brazil;
- Laboratório de Purificação de Proteínas e Suas Funções Biológicas (LPPFB), Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil;
| | - Maria Lígia Rodrigues Macedo
- Laboratório de Purificação de Proteínas e Suas Funções Biológicas (LPPFB), Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil;
| | - Kely de Picoli Souza
- Research Group on Biotechnology and Bioprospection Applied to Metabolism and Cancer (GEBBAM), Federal University of Grande Dourados, Dourados 79804-970, MS, Brazil;
| | - Paulo Matafome
- Coimbra Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal;
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal
- Clinical Academic Center of Coimbra, 3000-075 Coimbra, Portugal
- Coimbra Health School (ESTeSC), Polytechnic University of Coimbra, Rua 5 de Outubro, 3046-854 Coimbra, Portugal
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Cimas FJ, De la Cruz-Morcillo MÁ, Cifuentes C, Moratalla-López N, Alonso GL, Nava E, Llorens S. Effect of Crocetin on Basal Lipolysis in 3T3-L1 Adipocytes. Antioxidants (Basel) 2023; 12:1254. [PMID: 37371984 DOI: 10.3390/antiox12061254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 06/08/2023] [Accepted: 06/10/2023] [Indexed: 06/29/2023] Open
Abstract
Crocetin (CCT) is a natural saffron-derived apocarotenoid that possesses healthy properties such as anti-adipogenic, anti-inflammatory, and antioxidant activities. Lipolysis is enhanced in obesity and correlates with a pro-inflammatory, pro-oxidant state. In this context, we aimed to investigate whether CCT affects lipolysis. To evaluate CCT's possible lipolytic effect, 3T3-L1 adipocytes were treated with CCT10μM at day 5 post-differentiation. Glycerol content and antioxidant activity were assessed using colorimetric assays. Gene expression was measured using qRT-PCR to evaluate the effect of CCT on key lipolytic enzymes and on nitric oxide synthase (NOS) expression. Total lipid accumulation was assessed using Oil Red O staining. CCT10μM decreased glycerol release from 3T3-L1 adipocytes and downregulated adipose tissue triglyceride lipase (ATGL) and perilipin-1, but not hormone-sensitive lipase (HSL), suggesting an anti-lipolytic effect. CCT increased catalase (CAT) and superoxide dismutase (SOD) activity, thus showing an antioxidant effect. In addition, CCT exhibited an anti-inflammatory profile, i.e., diminished inducible NOS (NOS2) and resistin expression, while enhanced the expression of adiponectin. CCT10μM also decreased intracellular fat and C/EBPα expression (a transcription factor involved in adipogenesis), thus revealing an anti-adipogenic effect. These findings point to CCT as a promising biocompound for improving lipid mobilisation in obesity.
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Affiliation(s)
- Francisco J Cimas
- Mecenazgo COVID-19, Regional Center for Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), 02008 Albacete, Spain
| | - Miguel Ángel De la Cruz-Morcillo
- Food Quality Research Group, Institute for Regional Development (IDR), Campus Universitario s/n, University of Castilla-La Mancha (UCLM), 02071 Albacete, Spain
| | - Carmen Cifuentes
- Regional Center for Biomedical Research (CRIB), Department of Medical Sciences, Faculty of Medicine of Albacete, University of Castilla-La Mancha (UCLM), 02008 Albacete, Spain
| | - Natalia Moratalla-López
- Cátedra de Química Agrícola, Higher Technical School of Agronomic and Forestry Engineering and Biotechnology (ETSIAMB), University of Castilla-La Mancha (UCLM), Campus Universitario, 02006 Albacete, Spain
| | - Gonzalo L Alonso
- Cátedra de Química Agrícola, Higher Technical School of Agronomic and Forestry Engineering and Biotechnology (ETSIAMB), University of Castilla-La Mancha (UCLM), Campus Universitario, 02006 Albacete, Spain
| | - Eduardo Nava
- Regional Center for Biomedical Research (CRIB), Department of Medical Sciences, Faculty of Medicine of Albacete, University of Castilla-La Mancha (UCLM), 02008 Albacete, Spain
| | - Sílvia Llorens
- Regional Center for Biomedical Research (CRIB), Department of Medical Sciences, Faculty of Medicine of Albacete, University of Castilla-La Mancha (UCLM), 02008 Albacete, Spain
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Miao M, Bi Y, Hao L, Bao A, Sun Y, Du H, Song L, You S, Zhong C. Triglyceride-glucose index and short-term functional outcome and in-hospital mortality in patients with ischemic stroke. Nutr Metab Cardiovasc Dis 2023; 33:399-407. [PMID: 36586773 DOI: 10.1016/j.numecd.2022.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 10/12/2022] [Accepted: 11/01/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND AND AIMS The triglyceride-glucose (TyG) index has been demonstrated as an independent marker of ischemic stroke. Whether TyG index predicts short-term outcomes in patients with ischemic stroke remains uncertain. The aim of the study was to investigate the early prognosis value of TyG index in ischemic stroke patients. METHODS AND RESULTS A total of 3216 acute ischemic stroke patients from 22 hospitals were included in this analysis. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). Logistic regression model was performed to estimate the relationship between TyG index and unfavorable functional outcome of death or disability (modified Rankin Scale score of 4-6) at discharge. Risk reclassification with TyG index to predict unfavorable functional outcome was analyzed. During hospitalization, 748 patients (23.3%) experienced poor functional outcome and 105 patients (3.3%) died from all causes. The multivariable adjusted odds ratios for the highest versus lowest quartile of TyG index was 1.62 (95% CI 1.15-2.29) for unfavorable functional outcome at discharge. The addition of TyG index to the conventional model improved the risk reclassification (net reclassification improvement 10.37%; integrated discrimination improvement 0.27%; both p < 0.05) for poor functional outcome. Moreover, TyG index was associated with an odds ratio (95% CI) of 1.26 (1.02-1.55) for an ordinal shift in mRS score and 2.49 (1.21-5.12) for in-hospital mortality. CONCLUSIONS Higher TyG index was associated with higher risk of unfavorable functional outcome at discharge and in-hospital mortality, implicating the significant short-term prognostic effect of TyG index in patients with ischemic stroke.
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Affiliation(s)
- Mengyuan Miao
- Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China; Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yucong Bi
- Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China
| | - Lijun Hao
- Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Anran Bao
- Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China
| | - Yaming Sun
- Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou 215600, China
| | - Huaping Du
- Department of Neurology, The Affiliated Wujiang Hospital of Nantong University, Suzhou 215200, China
| | - Liyan Song
- Department of Neurology, The First People's Hospital of Taicang, Suzhou 215400, China
| | - Shoujiang You
- Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.
| | - Chongke Zhong
- Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China; Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.
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Potential Role of Oxidative Stress in the Production of Volatile Organic Compounds in Obesity. Antioxidants (Basel) 2023; 12:antiox12010129. [PMID: 36670991 PMCID: PMC9854577 DOI: 10.3390/antiox12010129] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 12/30/2022] [Accepted: 01/03/2023] [Indexed: 01/06/2023] Open
Abstract
Obesity is associated with numerous health issues such as sleep disorders, asthma, hepatic dysfunction, cancer, renal dysfunction, diabetes, cardiovascular complications, and infertility. Previous research has shown that the distribution of excess body fat, rather than excess body weight, determines obesity-related risk factors. It is widely accepted that abdominal fat is a serious risk factor for illnesses associated with obesity and the accumulation of visceral fat promotes the release of pro-oxidants, pro-inflammatory, and reactive oxygen species (ROS). The metabolic process in the human body produces several volatile organic compounds (VOCs) via urine, saliva, breath, blood, skin secretions, milk, and feces. Several studies have shown that VOCs are released by the interaction of ROS with underlying cellular components leading to increased protein oxidation, lipid peroxidation, or DNA damage. These VOCs released via oxidative stress in obese individuals may serves as a biomarker for obesity-related metabolic alterations and disease. In this review, we focus on the relationship between oxidative stress and VOCs in obesity.
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Kong ASY, Lai KS, Hee CW, Loh JY, Lim SHE, Sathiya M. Oxidative Stress Parameters as Biomarkers of Cardiovascular Disease towards the Development and Progression. Antioxidants (Basel) 2022; 11:antiox11061175. [PMID: 35740071 PMCID: PMC9219727 DOI: 10.3390/antiox11061175] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 06/03/2022] [Accepted: 06/06/2022] [Indexed: 12/12/2022] Open
Abstract
Cardiovascular disease (CVD) remains the leading cause of death globally, with unhealthy lifestyles today greatly increasing the risk. Over the decades, scientific investigation has been carried out on reactive oxygen species (ROS) and their resultant oxidative stress based on their changes made on biological targets such as lipids, proteins, and DNA. Since the existing clinical studies with antioxidants failed to provide relevant findings on CVD prediction, the focus has shifted towards recognition of oxidised targets as biomarkers to predict prognosis and response to accurate treatment. The identification of redox markers could help clinicians in providing risk stratification for CVD events beyond the traditional prognostic and diagnostic targets. This review will focus on how oxidant-related parameters can be applied as biomarkers for CVD based on recent clinical evidence.
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Affiliation(s)
- Amanda Shen-Yee Kong
- School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Subang Jaya 47500, Malaysia;
| | - Kok Song Lai
- Health Sciences Division, Abu Dhabi Women’s College, Higher Colleges of Technology, Abu Dhabi 41012, United Arab Emirates; (K.S.L.); (S.H.E.L.)
| | - Cheng-Wan Hee
- Faculty of Health and Life Sciences, INTI International University, Persiaran Perdana BBN, Putra Nilai, Nilai 71800, Malaysia;
| | - Jiun Yan Loh
- Centre of Research for Advanced Aquaculture (CORAA), UCSI University, Cheras, Kuala Lumpur 56000, Malaysia;
| | - Swee Hua Erin Lim
- Health Sciences Division, Abu Dhabi Women’s College, Higher Colleges of Technology, Abu Dhabi 41012, United Arab Emirates; (K.S.L.); (S.H.E.L.)
| | - Maran Sathiya
- School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Subang Jaya 47500, Malaysia;
- Correspondence:
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Cui C, Li T, Xie Y, Yang J, Fu C, Qiu Y, Shen L, Ni Q, Wang Q, Nie A, Ning G, Wang W, Gu Y. Enhancing Acsl4 in absence of mTORC2/Rictor drove β-cell dedifferentiation via inhibiting FoxO1 and promoting ROS production. Biochim Biophys Acta Mol Basis Dis 2021; 1867:166261. [PMID: 34455055 DOI: 10.1016/j.bbadis.2021.166261] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 08/16/2021] [Accepted: 08/24/2021] [Indexed: 02/07/2023]
Abstract
Rapamycin insensitive companion of mechanistic target of Rapamycin (Rictor), the key component of mTOR complex 2 (mTORC2), controls both β-cell proliferation and function. We sought to study whether long chain acyl-CoA synthetase 4 (Acsl4) worked downstream of Rictor/mTORC2 to maintain β-cell functional mass. We found Acsl4 was positively regulated by Rictor at transcriptional and posttranslational levels in mouse β-cell. Infecting adenovirus expressing Acsl4 in β-cell-specific-Rictor-knockout (βRicKO) islets and Min6 cells knocking down Rictor with lentivirus-expressing siRNA-oligos targeting Rictor(siRic), recovered the β-cell dysplasia but not dysfunction. Cell bioenergetic experiment performed with Seahorse XF showed that Acsl4 could not rescue the dampened glucose oxidation in Rictor-lacking β-cell, but further promoted lipid oxidation. Transposase-Accessible Chromatin (ATAC) and H3K27Ac chromatin immunoprecipitation (ChIP) sequencing studies reflected the epigenetic elevated molecular signature for β-cell dedifferentiation and mitigated oxidative defense/response. These results were confirmed by the observations of elevated acetylation and ubiquitination of FoxO1, increased protein levels of Gpx1 and Hif1an, excessive reactive oxygen species (ROS) production and diminished MafA in Acsl4 overexpressed Rictor-lacking β-cells. In these cells, antioxidant treatment significantly recovered MafA level and insulin content. Inducing lipid oxidation alone could not mimic the effect of Acsl4 in Rictor lacking β-cell. Our study suggested that Acsl4 function in β-cell was context dependent and might facilitate β-cell dedifferentiation with attenuated Rictor/mTORC2 activity or insulin signaling via posttranslational inhibiting FoxO1 and epigenetically enhancing ROS induced MafA degradation.
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Affiliation(s)
- Canqi Cui
- Shanghai National Research Centre for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tingting Li
- Shanghai National Research Centre for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yun Xie
- Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jie Yang
- Shanghai National Research Centre for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chenyang Fu
- Shanghai National Research Centre for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yixuan Qiu
- Shanghai National Research Centre for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Linyan Shen
- Shanghai National Research Centre for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qicheng Ni
- Shanghai National Research Centre for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qidi Wang
- Shanghai National Research Centre for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Aifang Nie
- Shanghai National Research Centre for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Guang Ning
- Shanghai National Research Centre for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Weiqing Wang
- Shanghai National Research Centre for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yanyun Gu
- Shanghai National Research Centre for Endocrine and Metabolic Diseases, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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12
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Wieland FC, Sthijns MMJPE, Geuens T, van Blitterswijk CA, LaPointe VLS. The Role of Pancreatic Alpha Cells and Endothelial Cells in the Reduction of Oxidative Stress in Pseudoislets. Front Bioeng Biotechnol 2021; 9:729057. [PMID: 34568302 PMCID: PMC8458707 DOI: 10.3389/fbioe.2021.729057] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 08/19/2021] [Indexed: 12/28/2022] Open
Abstract
Pancreatic beta cells have inadequate levels of antioxidant enzymes, and the damage induced by oxidative stress poses a challenge for their use in a therapy for patients with type 1 diabetes. It is known that the interaction of the pancreatic endocrine cells with support cells can improve their survival and lead to less vulnerability to oxidative stress. Here we investigated alpha (alpha TC-1), beta (INS1E) and endothelial (HUVEC) cells assembled into aggregates known as pseudoislets as a model of the pancreatic islets of Langerhans. We hypothesised that the coculture of alpha, beta and endothelial cells would be protective against oxidative stress. First, we showed that adding endothelial cells decreased the percentage of oxidative stress-positive cells. We then asked if the number of endothelial cells or the size (number of cells) of the pseudoislet could increase the protection against oxidative stress. However, no additional benefit was observed by those changes. On the other hand, we identified a potential supportive effect of the alpha cells in reducing oxidative stress in beta and endothelial cells. We were able to link this to the incretin glucagon-like peptide-1 (GLP-1) by showing that the absence of alpha cells in the pseudoislet caused increased oxidative stress, but the addition of GLP-1 could restore this. Together, these results provide important insights into the roles of alpha and endothelial cells in protecting against oxidative stress.
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Affiliation(s)
- Fredrik C Wieland
- MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands
| | - Mireille M J P E Sthijns
- MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands.,Centre for Healthy Eating and Food Innovation, Maastricht University, Maastricht, Netherlands
| | - Thomas Geuens
- MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands
| | - Clemens A van Blitterswijk
- MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands
| | - Vanessa L S LaPointe
- MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands
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13
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Zhou Y, Li H, Xia N. The Interplay Between Adipose Tissue and Vasculature: Role of Oxidative Stress in Obesity. Front Cardiovasc Med 2021; 8:650214. [PMID: 33748199 PMCID: PMC7969519 DOI: 10.3389/fcvm.2021.650214] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 02/10/2021] [Indexed: 12/15/2022] Open
Abstract
Cardiovascular diseases (CVDs) rank the leading cause of morbidity and mortality globally. Obesity and its related metabolic syndrome are well-established risk factors for CVDs. Therefore, understanding the pathophysiological role of adipose tissues is of great importance in maintaining cardiovascular health. Oxidative stress, characterized by excessive formation of reactive oxygen species, is a common cellular stress shared by obesity and CVDs. While plenty of literatures have illustrated the vascular oxidative stress, very few have discussed the impact of oxidative stress in adipose tissues. Adipose tissues can communicate with vascular systems, in an endocrine and paracrine manner, through secreting several adipocytokines, which is largely dysregulated in obesity. The aim of this review is to summarize current understanding of the relationship between oxidative stress in obesity and vascular endothelial dysfunction. In this review, we briefly describe the possible causes of oxidative stress in obesity, and the impact of obesity-induced oxidative stress on adipose tissue function. We also summarize the crosstalk between adipose tissue and vasculature mediated by adipocytokines in vascular oxidative stress. In addition, we highlight the potential target mediating adipose tissue oxidative stress.
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Affiliation(s)
- Yawen Zhou
- Department of Pharmacology, Johannes Gutenberg University Medical Center, Mainz, Germany
| | - Huige Li
- Department of Pharmacology, Johannes Gutenberg University Medical Center, Mainz, Germany
| | - Ning Xia
- Department of Pharmacology, Johannes Gutenberg University Medical Center, Mainz, Germany
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14
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Dragović G, Andjić M, Toljić B, Jevtović D, Lukić R, de Luka S, Trbovich A, Milašin J. Correlation between metabolic syndrome and relative telomere length shortening in HIV/AIDS patients on combined antiretroviral therapy. Exp Gerontol 2021; 147:111269. [PMID: 33529748 DOI: 10.1016/j.exger.2021.111269] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 12/20/2020] [Accepted: 01/29/2021] [Indexed: 01/07/2023]
Abstract
BACKGROUND Components of the metabolic syndrome (MetS) play an important role in the accelerated aging process. Relative telomere length (RTL) is a marker of biological aging. The aim of our study was to determine RTL and its possible association with MetS and the components of MetS in HIV-infected patients treated with cART. METHODS We included 24 HIV-infected men, all Caucasians, with successful cART (<50 HIV-RNA copies/mL) and on stable cART for at least 24 months. The presence of MetS and its components was determined by the criteria prescribed by the International Diabetes Federation. RTL was determined by Real-Time PCR and ΔΔCt method. We performed a multiple linear regression modeling on log-transformed RTL (dependant variable) to evaluate which components of the metabolic syndrome as well as cART duration and cART type, had an impact on RTL. RESULTS Eleven (45.8%) patients had and 13 (54.2%) had not MetS. All patients, had an undetectable viral RNA and a relatively good immune status. The mean RTL was 0.62 ± 0.15 and 0.95 ± 0.36 in patients with and without MetS, respectively (p = 0.01). Multiple linear regression model showed no significant association between duration of cART, cART type and RTL (p = 0.2165, p = 0.8628, respectively). The same analysis showed that an increase in number of MetS components was associated with shorter telomere length (β = -0.4982, p = 0.042). CONCLUSIONS We showed for the first time association between RTL shortening in HIV-infected men with metabolic syndrome. Furthermore, our study also indicated that an increment of metabolic syndrome components is strongly associated with shorter telomere length.
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Affiliation(s)
- Gordana Dragović
- Department of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Belgrade, Serbia.
| | - Mladen Andjić
- Department of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Boško Toljić
- Department of Human Genetics, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
| | - Djordje Jevtović
- Infectious and Tropical Diseases Hospital, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Relja Lukić
- Obstetrics/Gynaecology Clinic "Narodni front", School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Silvio de Luka
- Institute of Pathological Physiology, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Alexander Trbovich
- Institute of Pathological Physiology, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Jelena Milašin
- Department of Human Genetics, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
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15
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Zhang B, Liu L, Ruan H, Zhu Q, Yu D, Yang Y, Men X, Lu Z. Triglyceride-Glucose Index Linked to Hospital Mortality in Critically Ill Stroke: An Observational Multicentre Study on eICU Database. Front Med (Lausanne) 2020; 7:591036. [PMID: 33195355 PMCID: PMC7655911 DOI: 10.3389/fmed.2020.591036] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Accepted: 10/05/2020] [Indexed: 01/04/2023] Open
Abstract
Objective: The triglyceride-glucose (TyG) index is a reliable surrogate of insulin resistance and a marker for ischemic stroke (IS) incident. Whether the TyG index predicts stroke outcome remains uncertain. This study investigated the prognostic value of the TyG index in critically ill stroke patients. Methods: This was a retrospective observational study that included stroke patients, and all data were extracted from the eICU Collaborative Research Database. The TyG index was calculated as the ln [fasting glucose level (mg/dL) × triglyceride level (mg/dL)/2]. Outcomes included the hospital and intensive care unit (ICU) death. Multivariate logistic regression was used to determine independent risk factors. The smoothing curves and forest plots were illustrated. Results: A total of 4,570 eligible subjects were enrolled. The mean level of TyG index was 9.1 ± 0.7. The hospital and ICU mortality rate were 10.3 and 5.0%, respectively. TyG index as a continuous variable was associated hospital mortality in univariate analysis (OR 1.723, 95% CI 1.524-1.948, P < 0.001), adjusted model 1 (OR 1.861, 95% CI 1637-2.116, P < 0.001), and adjusted model 2 (OR 2.543, 95% CI 1.588-4.073, P < 0.001). TyG was also associated ICU mortality in univariate analysis (OR 2.146, 95% CI 1.826-2.523, P < 0.001), adjusted model 1 (OR 2.183, 95% CI 1.847-2.580, P < 0.001), and adjusted model 2 (OR 2.672, 95% CI 1.376-5.188, P < 0.001). The smoothing curves observed a continuous linear association after adjusting all covariates both in hospital and ICU mortality. Subgroup analysis demonstrated TyG index was associated with increased risk of hospital and ICU death in critically ill IS (P < 0.05), but not in hemorrhage stroke (P > 0.05). Conclusion: The TyG index is a potential predictor for hospital and ICU mortality in critically ill stroke patients, especially in IS patients.
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Affiliation(s)
- Bingjun Zhang
- Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lingling Liu
- Department of Hematology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Hengfang Ruan
- Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qiang Zhu
- Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Dafan Yu
- Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yu Yang
- Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xuejiao Men
- Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhengqi Lu
- Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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16
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Gao Y, Zhang S, Li J, Zhao J, Xiao Q, Zhu Y, Zhang J, Huang W. Effect and mechanism of ginsenoside Rg1-regulating hepatic steatosis in HepG2 cells induced by free fatty acid. Biosci Biotechnol Biochem 2020; 84:2228-2240. [PMID: 32654591 DOI: 10.1080/09168451.2020.1793293] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Ginsenoside Rg1 (G-Rg1) is a bioactive phytochemical that has been found to be beneficial for the treatment of several diseases including nonalcoholic fatty liver disease (NAFLD). But there is a lack of literature reporting the effect of G-Rg1 on lipid metabolism balance in NAFLD. We investigated the effect and mechanism of G-Rg1 on lipid metabolism in vitro. We found that G-Rg1 decreased the levels of TG, TC, and MDA, and increased activity of SOD. Results of RT-PCR and western blotting showed that supplementation with G-Rg1 downregulated the expression of PPAR γ, FABP1, FATP2/5, CD36, SREBP1 c, and FASN, while the expression of PPAR ɑ, CPT1, ACOX1, MTTP, and ApoB100 was upregulated, after induction by a free fatty acid. Taken together, we conclude that G-Rg1 inhibits lipid synthesis and lipid uptake, and enhances lipid oxidation and lipid export to reduce hepatic steatosis of HepG2 cells by regulating PPAR ɑ and PPAR γ expression.
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Affiliation(s)
- Yue Gao
- Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China
| | - Shujun Zhang
- Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China
| | - Jiajun Li
- Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China
| | - Jinqiu Zhao
- Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China
| | - Qing Xiao
- Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China
| | - Yali Zhu
- Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China
| | - Jia Zhang
- Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China
| | - Wenxiang Huang
- Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China
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17
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Xu W, Zhao T, Xiao H. The Implication of Oxidative Stress and AMPK-Nrf2 Antioxidative Signaling in Pneumonia Pathogenesis. Front Endocrinol (Lausanne) 2020; 11:400. [PMID: 32625169 PMCID: PMC7311749 DOI: 10.3389/fendo.2020.00400] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Accepted: 05/18/2020] [Indexed: 02/05/2023] Open
Abstract
It is widely recognized that chemical, physical, and biological factors can singly or synergistically evoke the excessive production of oxidative stress in pulmonary tissue that followed by pulmonary lesions and pneumonia. In addition, metabolic and endocrine disorder-induced diseases such as diabetes and obesity often expressed higher susceptibility to pulmonary infections, and presented severe symptoms which increasing the mortality rate. Therefore, the connection between the lesion of the lungs and the metabolic/endocrine disorders is an interesting and essential issue to be addressed. Studies have noticed a similar pathological feature in both infectious pneumonia and metabolic disease-intercurrent pulmonary lesions, that is, from the view of molecular pathology, the accumulation of excessive reactive oxygen species (ROS) in pulmonary tissue accompanying with activated pro-inflammatory signals. Meanwhile, Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and nuclear factor erythroid-2-related factor 2 (Nrf2) signaling plays important role in metabolic/endocrine homeostasis and infection response, and it's closely associated with the anti-oxidative capacity of the body. For this reason, this review will start from the summary upon the implication of ROS accumulation, and to discuss how AMPK-Nrf2 signaling contributes to maintaining the metabolic/endocrine homeostasis and attenuates the susceptibility of pulmonary infections.
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Affiliation(s)
| | | | - Hengyi Xiao
- Lab for Aging Research, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
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18
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Sotomayor CG, Minović I, Eggersdorfer ML, Riphagen IJ, de Borst MH, Dekker LH, Nolte IM, Frank J, van Zon SK, Reijneveld SA, van der Molen JC, Vos MJ, Kootstra-Ros JE, Rodrigo R, Kema IP, Navis GJ, Bakker SJ. Duality of Tocopherol Isoforms and Novel Associations with Vitamins Involved in One-Carbon Metabolism: Results from an Elderly Sample of the LifeLines Cohort Study. Nutrients 2020; 12:580. [PMID: 32102191 PMCID: PMC7071362 DOI: 10.3390/nu12020580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Revised: 02/18/2020] [Accepted: 02/19/2020] [Indexed: 11/16/2022] Open
Abstract
Whether the affinity of serum vitamin E with total lipids hampers the appropriate assessment of its association with age-related risk factors has not been investigated in epidemiological studies. We aimed to compare linear regression-derived coefficients of the association of non-indexed and total lipids-indexed vitamin E isoforms with clinical and laboratory characteristics pertaining to the lipid, metabolic syndrome, and one-carbon metabolism biological domains. We studied 1429 elderly subjects (non-vitamin supplement users, 60-75 years old, with low and high socioeconomic status) from the population-based LifeLines Cohort and Biobank Study. We found that the associations of tocopherol isoforms with lipids were inverted in total lipids-indexed analyses, which may be indicative of overcorrection. Irrespective of the methods of standardization, we consistently found positive associations of α-tocopherol with vitamins of the one-carbon metabolism pathway and inverse associations with characteristics related to glucose metabolism. The associations of γ-tocopherol were often opposite to those of α-tocopherol. These data suggest that tocopherol isoforms and one-carbon metabolism are related, with beneficial and adverse associations for α-tocopherol and γ-tocopherol, respectively. Whether tocopherol isoforms, or their interplay, truly affect the one-carbon metabolism pathway remains to be further studied.
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Affiliation(s)
- Camilo G. Sotomayor
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (M.L.E.); (M.H.d.B.); (L.H.D.); (G.J.N.)
| | - Isidor Minović
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (I.M.); (I.J.R.); (J.C.v.d.M.); (M.J.V.); (J.E.K.-R.); (I.P.K.)
| | - Manfred L. Eggersdorfer
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (M.L.E.); (M.H.d.B.); (L.H.D.); (G.J.N.)
| | - Ineke J. Riphagen
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (I.M.); (I.J.R.); (J.C.v.d.M.); (M.J.V.); (J.E.K.-R.); (I.P.K.)
| | - Martin H. de Borst
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (M.L.E.); (M.H.d.B.); (L.H.D.); (G.J.N.)
| | - Louise H. Dekker
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (M.L.E.); (M.H.d.B.); (L.H.D.); (G.J.N.)
| | - Ilja M. Nolte
- Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands;
| | - Jan Frank
- Institute of Nutritional Sciences, University of Hohenheim, 70599 Stuttgart, Germany;
| | - Sander K.R. van Zon
- Department of Health Sciences, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands (S.A.R.)
| | - Sijmen A. Reijneveld
- Department of Health Sciences, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands (S.A.R.)
| | - Jan C. van der Molen
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (I.M.); (I.J.R.); (J.C.v.d.M.); (M.J.V.); (J.E.K.-R.); (I.P.K.)
| | - Michel J. Vos
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (I.M.); (I.J.R.); (J.C.v.d.M.); (M.J.V.); (J.E.K.-R.); (I.P.K.)
| | - Jenny E. Kootstra-Ros
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (I.M.); (I.J.R.); (J.C.v.d.M.); (M.J.V.); (J.E.K.-R.); (I.P.K.)
| | - Ramón Rodrigo
- Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago CP 8380453, Chile;
| | - Ido P. Kema
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (I.M.); (I.J.R.); (J.C.v.d.M.); (M.J.V.); (J.E.K.-R.); (I.P.K.)
| | - Gerjan J. Navis
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (M.L.E.); (M.H.d.B.); (L.H.D.); (G.J.N.)
| | - Stephan J.L. Bakker
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (M.L.E.); (M.H.d.B.); (L.H.D.); (G.J.N.)
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19
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Ju J, Zheng Z, Xu YJ, Cao P, Li J, Li Q, Liu Y. Influence of total polar compounds on lipid metabolism, oxidative stress and cytotoxicity in HepG2 cells. Lipids Health Dis 2019; 18:37. [PMID: 30709407 PMCID: PMC6359786 DOI: 10.1186/s12944-019-0980-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Accepted: 01/21/2019] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Recently, the harmful effects of frying oil on health have been gradually realized. However, as main components of frying oils, biochemical effects of total polar compounds (TPC) on a cellular level were underestimated. METHODS The effects of total polar compounds (TPC) in the frying oil on the lipid metabolism, oxidative stress and cytotoxicity of HepG2 cells were investigated through a series of biochemical methods, such as oil red staining, real-time polymerase chain reaction (RT-PCR), cell apoptosis and cell arrest. RESULTS Herein, we found that the survival rate of HepG2 cells treated with TPC decreased in a time and dose dependent manner, and thereby presented significant lipid deposition over the concentration of 0.5 mg/mL. TPC were also found to suppress the expression levels of PPARα, CPT1 and ACOX, elevate the expression level of MTP and cause the disorder of lipid metabolism. TPC ranged from 0 to 2 mg/mL could significantly elevate the amounts of reactive oxygen species (ROS) in HepG2 cells, and simultaneously increase the malondialdehyde (MDA) content from 21.21 ± 2.62 to 65.71 ± 4.20 μmol/mg of protein (p < 0.05) at 24 h. On the contrary, antioxidant enzymes superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) respectively decreased by 0.52-, 0.56- and 0.28-fold, when HepG2 cells were exposed to 2 mg/mL TPC for 24 h. In addition, TPC could at least partially induce the apoptosis of HepG2 cells, and the transition from G0/G1 to G2 phase in HepG2 cells was impeded. CONCLUSIONS TPC could progressively cause lipid deposition, oxidative stress and cytotoxicity, providing the theoretical support for the detrimental health effects of TPC.
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Affiliation(s)
- Jingjie Ju
- School of Food Science and Technology, National Engineering Laboratory for Cereal Fermentation Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, Jiangsu, People's Republic of China
| | - Zhaojun Zheng
- School of Food Science and Technology, National Engineering Laboratory for Cereal Fermentation Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, Jiangsu, People's Republic of China
| | - Yong-Jiang Xu
- School of Food Science and Technology, National Engineering Laboratory for Cereal Fermentation Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, Jiangsu, People's Republic of China
| | - Peirang Cao
- School of Food Science and Technology, National Engineering Laboratory for Cereal Fermentation Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, Jiangsu, People's Republic of China
| | - Jingwei Li
- School of Food Science and Technology, National Engineering Laboratory for Cereal Fermentation Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, Jiangsu, People's Republic of China
| | - Qiu Li
- Shandong LuHua group co., LTD, Laiyang, 265200, People's Republic of China
| | - Yuanfa Liu
- School of Food Science and Technology, National Engineering Laboratory for Cereal Fermentation Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, Jiangsu, People's Republic of China.
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20
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Zaborska KE, Wareing M, Austin C. Comparisons between perivascular adipose tissue and the endothelium in their modulation of vascular tone. Br J Pharmacol 2017; 174:3388-3397. [PMID: 27747871 PMCID: PMC5610163 DOI: 10.1111/bph.13648] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Revised: 09/16/2016] [Accepted: 09/28/2016] [Indexed: 01/06/2023] Open
Abstract
The endothelium is an established modulator of vascular tone; however, the recent discovery of the anti-contractile nature of perivascular adipose tissue (PVAT) suggests that the fat, which surrounds many blood vessels, can also modulate vascular tone. Both the endothelium and PVAT secrete vasoactive substances, which regulate vascular function. Many of these factors are common to both the endothelium and PVAT; therefore, this review will highlight the potential shared mechanisms in the modulation of vascular tone. Endothelial dysfunction is a hallmark of many vascular diseases, including hypertension and obesity. Moreover, PVAT dysfunction is now being reported in several cardio-metabolic disorders. Thus, this review will also discuss the mechanistic insights into endothelial and PVAT dysfunction in order to evaluate whether PVAT modulation of vascular contractility is similar to that of the endothelium in health and disease. LINKED ARTICLES This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc.
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Affiliation(s)
- K E Zaborska
- Institute of Cardiovascular SciencesUniversity of ManchesterUK
| | - M Wareing
- Maternal and Fetal Health Research Centre, Institute of Human DevelopmentUniversity of ManchesterUK
| | - C Austin
- Faculty of Health and Social CareEdge Hill UniversityUK
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21
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Dhanda N, Taheri S. A narrative review of obesity and hearing loss. Int J Obes (Lond) 2017; 41:1066-1073. [PMID: 28163314 DOI: 10.1038/ijo.2017.32] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Revised: 12/18/2016] [Accepted: 01/23/2017] [Indexed: 12/20/2022]
Abstract
The comorbidities related to obesity are already extensive, but as the prevalence of obesity increases globally, so do the number of its associated conditions. The relationship between hearing impairment and obesity is a relatively recent research interest, but is significant as both conditions have the ability to substantially reduce an individual's quality of life both physically and psychologically. Obesity has a significant effect on vascular function, and this may have an impact on highly vascular organs such as the auditory system. This review aims to provide an overview of the existing literature surrounding the association between hearing loss and obesity, in order to emphasise these two highly prevalent conditions, and to identify areas of further investigation. Our literature search identified a total of 298 articles with 11 articles of relevance to the review. The existing literature in this area is sparse, with interest ranging from obesity and its links to age-related hearing impairment (ARHI) and sudden sensorineural hearing loss (SSNHL), to animal models and genetic syndromes that incorporate both disorders. A key hypothesis for the underlying mechanism for the relationship between obesity and hearing loss is that of vasoconstriction in the inner ear, whereby strain on the capillary walls due to excess adipose tissue causes damage to the delicate inner ear system. The identified articles in this review have not established a causal relationship between obesity and hearing impairment. Further research is required to examine the emerging association between obesity and hearing impairment, and identify its potential underlying mechanisms.
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Affiliation(s)
- N Dhanda
- Clinical Research Core, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - S Taheri
- Clinical Research Core, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar.,Department of Medicine, Weill Cornell Medicine, New York, NY, USA
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22
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Karimi K, Lindgren TH, Koch CA, Brodell RT. Obesity as a risk factor for malignant melanoma and non-melanoma skin cancer. Rev Endocr Metab Disord 2016; 17:389-403. [PMID: 27832418 DOI: 10.1007/s11154-016-9393-9] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The dramatic increases in incidence of both obesity and many cancers including skin cancer emphasize the need to better understand the pathophysiology of both conditions and their connections. Melanoma is considered the fastest growing cancer and rates of non-melanoma skin cancer have also increased over the last decade. The molecular mechanisms underlying the association between obesity and skin cancer are not clearly understood but emerging evidence points to changes in the tumor microenvironment including aberrant cell signaling and genomic instability in the chronic inflammatory state many obese individuals experience. This article reviews the literature linking obesity to melanoma and non-melanoma skin cancer.
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Affiliation(s)
- K Karimi
- School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - T H Lindgren
- School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - C A Koch
- Division of Endocrinology, University of Mississippi Medical Center, Jackson, MS, USA
- Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA
- G.V. (Sonny) Montgomery VA Medical Center, Jackson, MS, USA
| | - Robert T Brodell
- Department of Dermatology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.
- Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA.
- Department of Dermatology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
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Manna P, Jain SK. Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies. Metab Syndr Relat Disord 2016; 13:423-44. [PMID: 26569333 DOI: 10.1089/met.2015.0095] [Citation(s) in RCA: 687] [Impact Index Per Article: 76.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue in development of these risk factors, and potential strategies to regulate body weight loss/gain for better health benefits.
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Affiliation(s)
- Prasenjit Manna
- Department of Pediatrics, LSU Health Sciences Center , Shreveport, Louisiana
| | - Sushil K Jain
- Department of Pediatrics, LSU Health Sciences Center , Shreveport, Louisiana
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24
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Ramesh B, Sainath S, Karuna R, Sreenivasa Reddy S, Manjunatha B, Sudhakara G, Sasi Bhusana Rao B, Saralakumari D. Effect of Commiphora mukul gum resin on hepatic and renal marker enzymes, lipid peroxidation and antioxidants status in pancreas and heart in fructose fed insulin resistant rats. BENI-SUEF UNIVERSITY JOURNAL OF BASIC AND APPLIED SCIENCES 2015. [DOI: 10.1016/j.bjbas.2015.11.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
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25
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Erukainure OL, Okafor O, Ajayi A, Obode O, Ogunji A, Okporua T, Suberu Y, Oke O, Ozumba A, Oluwole O, Elemo G. Developed beverage from roselle calyx and selected fruits modulates β-cell function, improves insulin sensitivity, and attenuates hyperlipidaemia in diabetic rats. BENI-SUEF UNIVERSITY JOURNAL OF BASIC AND APPLIED SCIENCES 2015. [DOI: 10.1016/j.bjbas.2015.11.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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26
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New Insight into the Role of Reactive Oxygen Species (ROS) in Cellular Signal-Transduction Processes. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2015; 319:221-54. [PMID: 26404470 DOI: 10.1016/bs.ircmb.2015.07.004] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Reactive oxygen species (ROS) were once considered to be deleterious agents, contributing to a vast range of pathologies. But, now their protective effects are being appreciated. Both their damaging and beneficial effects are initiated when they target distinct molecules and consequently begin functioning as part of complex signal-transduction pathways. The recognition of ROS as signaling mediators has driven a wealth of research into their roles in both normal and pathophysiological states. The present review assesses the relevant recent literature to outline the current perspectives on redox-signaling mechanisms, physiological implications, and therapeutic strategies. This study highlights that a more fundamental knowledge about many aspects of redox signaling will allow better targeting of ROS, which would in turn improve prophylactic and pharmacotherapy for redox-associated diseases.
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27
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Goszcz K, Deakin SJ, Duthie GG, Stewart D, Leslie SJ, Megson IL. Antioxidants in Cardiovascular Therapy: Panacea or False Hope? Front Cardiovasc Med 2015; 2:29. [PMID: 26664900 PMCID: PMC4671344 DOI: 10.3389/fcvm.2015.00029] [Citation(s) in RCA: 108] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Accepted: 06/10/2015] [Indexed: 12/31/2022] Open
Abstract
Oxidative stress is a key feature of the atherothrombotic process involved in the etiology of heart attacks, ischemic strokes, and peripheral arterial disease. It stands to reason that antioxidants represent a credible therapeutic option to prevent disease progression and thereby improve outcome, but despite positive findings from in vitro studies, clinical trials have failed to consistently show benefit. The aim of this review is to re-appraise the concept of antioxidants in the prevention and management of cardiovascular disease. In particular, the review will explore the reasons behind failed antioxidant strategies with vitamin supplements and will evaluate how flavonoids might improve cardiovascular function despite bioavailability that is not sufficiently high to directly influence antioxidant capacity. As well as reaching conclusions relating to those antioxidant strategies that might hold merit, the major myths, limitations, and pitfalls associated with this research field are explored.
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Affiliation(s)
- Katarzyna Goszcz
- Department of Diabetes and Cardiovascular Science, Centre for Health Science, University of the Highlands and Islands , Inverness , UK ; James Hutton Institute , Dundee , UK
| | - Sherine J Deakin
- Department of Diabetes and Cardiovascular Science, Centre for Health Science, University of the Highlands and Islands , Inverness , UK
| | - Garry G Duthie
- Rowett Institute of Health and Nutrition , Aberdeen , UK
| | - Derek Stewart
- James Hutton Institute , Dundee , UK ; School of Life Sciences, Heriot Watt University , Edinburgh , UK
| | - Stephen J Leslie
- Department of Diabetes and Cardiovascular Science, Centre for Health Science, University of the Highlands and Islands , Inverness , UK ; Cardiology Unit, Raigmore Hospital , Inverness , UK
| | - Ian L Megson
- Department of Diabetes and Cardiovascular Science, Centre for Health Science, University of the Highlands and Islands , Inverness , UK
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28
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Roussel J, Thireau J, Brenner C, Saint N, Scheuermann V, Lacampagne A, Le Guennec JY, Fauconnier J. Palmitoyl-carnitine increases RyR2 oxidation and sarcoplasmic reticulum Ca2+ leak in cardiomyocytes: Role of adenine nucleotide translocase. Biochim Biophys Acta Mol Basis Dis 2015; 1852:749-58. [DOI: 10.1016/j.bbadis.2015.01.011] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2014] [Revised: 01/16/2015] [Accepted: 01/18/2015] [Indexed: 12/30/2022]
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Tangvarasittichai S. Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World J Diabetes 2015; 6:456-480. [PMID: 25897356 PMCID: PMC4398902 DOI: 10.4239/wjd.v6.i3.456] [Citation(s) in RCA: 751] [Impact Index Per Article: 75.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Revised: 11/21/2014] [Accepted: 01/12/2015] [Indexed: 02/05/2023] Open
Abstract
Oxidative stress is increased in metabolic syndrome and type 2 diabetes mellitus (T2DM) and this appears to underlie the development of cardiovascular disease, T2DM and diabetic complications. Increased oxidative stress appears to be a deleterious factor leading to insulin resistance, dyslipidemia, β-cell dysfunction, impaired glucose tolerance and ultimately leading to T2DM. Chronic oxidative stress, hyperglycemia and dyslipidemia are particularly dangerous for β-cells from lowest levels of antioxidant, have high oxidative energy requirements, decrease the gene expression of key β-cell genes and induce cell death. If β-cell functioning is impaired, it results in an under production of insulin, impairs glucose stimulated insulin secretion, fasting hyperglycemia and eventually the development of T2DM.
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Alkhalidy H, Moore W, Zhang Y, McMillan R, Wang A, Ali M, Suh KS, Zhen W, Cheng Z, Jia Z, Hulver M, Liu D. Small Molecule Kaempferol Promotes Insulin Sensitivity and Preserved Pancreatic β -Cell Mass in Middle-Aged Obese Diabetic Mice. J Diabetes Res 2015; 2015:532984. [PMID: 26064984 PMCID: PMC4439495 DOI: 10.1155/2015/532984] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Revised: 04/09/2015] [Accepted: 04/20/2015] [Indexed: 12/20/2022] Open
Abstract
Insulin resistance and a progressive decline in functional β-cell mass are hallmarks of developing type 2 diabetes (T2D). Thus, searching for natural, low-cost compounds to target these two defects could be a promising strategy to prevent the pathogenesis of T2D. Here, we show that dietary intake of flavonol kaempferol (0.05% in the diet) significantly ameliorated hyperglycemia, hyperinsulinemia, and circulating lipid profile, which were associated with the improved peripheral insulin sensitivity in middle-aged obese mice fed a high-fat (HF) diet. Kaempferol treatment reversed HF diet impaired glucose transport-4 (Glut4) and AMP-dependent protein kinase (AMPK) expression in both muscle and adipose tissues from obese mice. In vitro, kaempferol increased lipolysis and prevented high fatty acid-impaired glucose uptake, glycogen synthesis, AMPK activity, and Glut4 expression in skeletal muscle cells. Using another mouse model of T2D generated by HF diet feeding and low doses of streptozotocin injection, we found that kaempferol treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in obese diabetic mice, which are associated with the improved islet β-cell mass. These results demonstrate that kaempferol may be a naturally occurring anti-diabetic agent by improving peripheral insulin sensitivity and protecting against pancreatic β-cell dysfunction.
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Affiliation(s)
- Hana Alkhalidy
- Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA
| | - William Moore
- Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA
| | - Yanling Zhang
- Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA
| | - Ryan McMillan
- Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA
- The Metabolic Phenotyping Core, Virginia Tech, Blacksburg, VA 24061, USA
| | - Aihua Wang
- Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA
| | - Mostafa Ali
- Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA
| | - Kyung-Shin Suh
- Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA
| | - Wei Zhen
- Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA
| | - Zhiyong Cheng
- Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA
| | - Zhenquan Jia
- Department of Biology, The University of North Carolina at Greensboro, Greensboro, NC 27412, USA
| | - Matthew Hulver
- Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA
| | - Dongmin Liu
- Department of Human Nutrition, Foods & Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA
- *Dongmin Liu:
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31
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García-Prieto CF, Hernández-Nuño F, Rio DD, Ruiz-Hurtado G, Aránguez I, Ruiz-Gayo M, Somoza B, Fernández-Alfonso MS. High-fat diet induces endothelial dysfunction through a down-regulation of the endothelial AMPK-PI3K-Akt-eNOS pathway. Mol Nutr Food Res 2014; 59:520-32. [PMID: 25421217 DOI: 10.1002/mnfr.201400539] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2014] [Revised: 11/08/2014] [Accepted: 11/13/2014] [Indexed: 11/11/2022]
Abstract
SCOPE Activation of endothelial adenosine monophosphate-activated protein kinase (AMPK) contributes to increase nitric oxide (NO) availability. The aim of this study was to assess if high-fat diet (HFD)-induced endothelial dysfunction is linked to AMPK deregulation. METHODS AND RESULTS Twelve-week-old Sprague Dawley male rats were assigned either to control (10 kcal % from fat) or to HFD (45 kcal % from fat) for 8 wk. HFD rats segregated in obesity-prone (OP) or obesity-resistant (OR) rats according to body weight. HFD triggered an impaired glucose management together with impaired endothelium-dependent relaxation, reduced endothelial AMPK activity and lower NO availability in aortic rings of OP and OR cohorts. Relaxation evoked by AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) was reduced in both OP and OR rings, which exhibited lower p-AMPKα-Thr(172) /AMPKα ratios that negatively correlated with plasma non-esterified fatty acids (NEFA) and triglycerides (TG). Inhibition of PI3K (wortmannin, 10(-7) M) or Akt (triciribine, 10(-5) M) reduced relaxation to AICAR only in the control group (p < 0.001). Akt (p-Akt-Ser(473) ) and eNOS phosphorylation (p-eNOS-Ser(1177) ) were significantly reduced in OP and OR (p < 0.01). CONCLUSION Endothelial dysfunction caused by HFD is related to a dysfunctional endothelial AMPK-PI3K-Akt-eNOS pathway correlating with the increase of plasma NEFA, TG, and an impaired glucose management.
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Affiliation(s)
- Concha F García-Prieto
- Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, Madrid, Spain
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32
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Aon MA, Bhatt N, Cortassa SC. Mitochondrial and cellular mechanisms for managing lipid excess. Front Physiol 2014; 5:282. [PMID: 25132820 PMCID: PMC4116787 DOI: 10.3389/fphys.2014.00282] [Citation(s) in RCA: 178] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2014] [Accepted: 07/10/2014] [Indexed: 12/16/2022] Open
Abstract
Current scientific debates center on the impact of lipids and mitochondrial function on diverse aspects of human health, nutrition and disease, among them the association of lipotoxicity with the onset of insulin resistance in skeletal muscle, and with heart dysfunction in obesity and diabetes. Mitochondria play a fundamental role in aging and in prevalent acute or chronic diseases. Lipids are main mitochondrial fuels however these molecules can also behave as uncouplers and inhibitors of oxidative phosphorylation. Knowledge about the functional composition of these contradictory effects and their impact on mitochondrial-cellular energetics/redox status is incomplete. Cells store fatty acids (FAs) as triacylglycerol and package them into cytoplasmic lipid droplets (LDs). New emerging data shows the LD as a highly dynamic storage pool of FAs that can be used for energy reserve. Lipid excess packaging into LDs can be seen as an adaptive response to fulfilling energy supply without hindering mitochondrial or cellular redox status and keeping low concentration of lipotoxic intermediates. Herein we review the mechanisms of action and utilization of lipids by mitochondria reported in liver, heart and skeletal muscle under relevant physiological situations, e.g., exercise. We report on perilipins, a family of proteins that associate with LDs in response to loading of cells with lipids. Evidence showing that in addition to physical contact, mitochondria and LDs exhibit metabolic interactions is presented and discussed. A hypothetical model of channeled lipid utilization by mitochondria is proposed. Direct delivery and channeled processing of lipids in mitochondria could represent a reliable and efficient way to maintain reactive oxygen species (ROS) within levels compatible with signaling while ensuring robust and reliable energy supply.
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Affiliation(s)
- Miguel A Aon
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine Baltimore, MD, USA
| | - Niraj Bhatt
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine Baltimore, MD, USA
| | - Sonia C Cortassa
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine Baltimore, MD, USA
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Pawitra P, Achida J, Benjamart C, Sakulrat R, Somsak N. Anti-lipolytic, -amylase inhibitory and antioxidant activities of Pseuderanthemum palatiferum (Nees) Radlk. leaf ethanolic extract. ACTA ACUST UNITED AC 2014. [DOI: 10.5897/jmpr2014.5480] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
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Gamboa-Gómez C, Salgado LM, González-Gallardo A, Ramos-Gómez M, Loarca-Piña G, Reynoso-Camacho R. Consumption of Ocimum sanctum L. and Citrus paradisi infusions modulates lipid metabolism and insulin resistance in obese rats. Food Funct 2014; 5:927-35. [DOI: 10.1039/c3fo60604j] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
A high saturated fat and fructose diet leads to metabolic disorders through dysregulation of genes involved in lipid metabolism.
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Affiliation(s)
- Claudia Gamboa-Gómez
- Research and Graduate Studies in Food Science
- Universidad Autonoma de Queretaro
- Queretaro, Mexico
| | - Luis M. Salgado
- Instituto Politécnico Nacional
- CICATA-Unidad Queretaro
- Queretaro, Mexico
| | - Adriana González-Gallardo
- Unidad de Proteogenomica
- Instituto de Neurobiologia
- Universidad Nacional Autonoma de Mexico
- Queretaro, Mexico
| | - Minerva Ramos-Gómez
- Research and Graduate Studies in Food Science
- Universidad Autonoma de Queretaro
- Queretaro, Mexico
| | - Guadalupe Loarca-Piña
- Research and Graduate Studies in Food Science
- Universidad Autonoma de Queretaro
- Queretaro, Mexico
| | - Rosalía Reynoso-Camacho
- Research and Graduate Studies in Food Science
- Universidad Autonoma de Queretaro
- Queretaro, Mexico
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Abstract
Obesity currently affects about one-third of the U.S. population, while another one-third is overweight. The importance of obesity for certain conditions such as heart disease and type 2 diabetes is well appreciated. The effects of obesity on the respiratory system have received less attention and are the subject of this article. Obesity alters the static mechanical properties of the respiratory system leading to a reduction in the functional residual capacity (FRC) and the expiratory reserve volume (ERV). There is substantial variability in the effects of obesity on FRC and ERV, at least some of which is related to the location rather than the total mass of adipose tissue. Obesity also results in airflow obstruction, which is only partially attributable to breathing at low lung volume, and can also promote airway hyperresponsiveness and asthma. Hypoxemia is common is obesity and correlates well with FRC, as well as with measures of abdominal obesity. However, obese subjects are usually eucapnic, indicating that hypoventilation is not a common cause of their hypoxemia. Instead, hypoxemia results from ventilation-perfusion mismatch caused by closure of dependent airways at FRC. Many obese subjects complain of dyspnea either at rest or during exertion, and the dyspnea score also correlates with reductions in FRC and ERV. Weight reduction should be encouraged in any symptomatic obese individual, since virtually all of the respiratory complications of obesity improve with even moderate weight loss.
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Alberici LC, Paim BA, Zecchin KG, Mirandola SR, Pestana CR, Castilho RF, Vercesi AE, Oliveira HCF. Activation of the mitochondrial ATP-sensitive K+ channel reduces apoptosis of spleen mononuclear cells induced by hyperlipidemia. Lipids Health Dis 2013; 12:87. [PMID: 23764148 PMCID: PMC3693968 DOI: 10.1186/1476-511x-12-87] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2013] [Accepted: 06/10/2013] [Indexed: 01/09/2023] Open
Abstract
Background We have previously demonstrated that increased rates of superoxide generation by extra-mitochondrial enzymes induce the activation of the mitochondrial ATP-sensitive potassium channel (mitoKATP) in the livers of hypertriglyceridemic (HTG) mice. The resulting mild uncoupling mediated by mitoKATP protects mitochondria against oxidative damage. In this study, we investigate whether immune cells from HTG mice also present increased mitoKATP activity and evaluate the influence of this trait on cell redox state and viability. Methods Oxygen consumption (Clark-type electrode), reactive oxygen species production (dihydroethidium and H2-DCF-DA probes) and cell death (annexin V, cytocrome c release and Trypan blue exclusion) were determined in spleen mononuclear cells. Results HTG mice mononuclear cells displayed increased mitoKATP activity, as evidenced by higher resting respiration rates that were sensitive to mitoKATP antagonists. Whole cell superoxide production and apoptosis rates were increased in HTG cells. Inhibition of mitoKATP further increased the production of reactive oxygen species and apoptosis in these cells. Incubation with HTG serum induced apoptosis more strongly in WT cells than in HTG mononuclear cells. Cytochrome c release into the cytosol and caspase 8 activity were both increased in HTG cells, indicating that cell death signaling starts upstream of the mitochondria but does involve this organelle. Accordingly, a reduced number of blood circulating lymphocytes was found in HTG mice. Conclusions These results demonstrate that spleen mononuclear cells from hyperlipidemic mice have more active mitoKATP channels, which downregulate mitochondrial superoxide generation. The increased apoptosis rate observed in these cells is exacerbated by closing the mitoKATP channels. Thus, mitoKATP opening acts as a protective mechanism that reduces cell death induced by hyperlipidemia.
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Affiliation(s)
- Luciane C Alberici
- Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil
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Karunakaran U, Park KG. A systematic review of oxidative stress and safety of antioxidants in diabetes: focus on islets and their defense. Diabetes Metab J 2013; 37:106-12. [PMID: 23641350 PMCID: PMC3638220 DOI: 10.4093/dmj.2013.37.2.106] [Citation(s) in RCA: 142] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
A growing body of evidence suggests that hyperglycemia-induced oxidative stress plays an important role in diabetic complications, especially β-cell dysfunction and failure. Under physiological conditions, reactive oxygen species serve as second messengers that facilitate signal transduction and gene expression in pancreatic β-cells. However, under pathological conditions, an imbalance in redox homeostasis leads to aberrant tissue damage and β-cell death due to a lack of antioxidant defense systems. Taking into account the vulnerability of islets to oxidative damage, induction of endogenous antioxidant enzymes or exogenous antioxidant administration has been proposed as a way to protect β-cells against diabetic insults. Here, we consider recent insights into how the redox response becomes deregulated under diabetic conditions, as well as the therapeutic benefits of antioxidants, which may provide clues for developing strategies aimed at the treatment or prevention of diabetes associated with β-cell failure.
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Affiliation(s)
- Udayakumar Karunakaran
- Departments of Internal Medicine, Biochemistry and Cell Biology, Research Institute of Aging and Metabolism and World Class University Program, Kyungpook National University School of Medicine, Daegu, Korea
| | - Keun-Gyu Park
- Departments of Internal Medicine, Biochemistry and Cell Biology, Research Institute of Aging and Metabolism and World Class University Program, Kyungpook National University School of Medicine, Daegu, Korea
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Eizadi M, Bagheri G, Kasparast J, Zahedmanesh F, Afsharmand Z. Effects of training on body composition, blood lipids, and glucose homeostasis assessed by the homeostasis model assessment. Sci Sports 2013. [DOI: 10.1016/j.scispo.2012.01.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Reddy PY, Giridharan NV, Balakrishna N, Validandi V, Pullakhandam R, Reddy GB. Increased risk of cataract development in WNIN-obese rats due to accumulation of intralenticular sorbitol. IUBMB Life 2013; 65:472-8. [PMID: 23504868 DOI: 10.1002/iub.1163] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2013] [Revised: 01/26/2013] [Accepted: 01/31/2013] [Indexed: 11/08/2022]
Abstract
Epidemiological studies have reported an association between obesity and increased incidence of ocular complications including cataract, yet the underlying biochemical and molecular mechanisms remained unclear. Previously we had demonstrated accumulation of sorbitol in the lens of obese rats (WNIN/Ob) and more so in a related strain with impaired glucose tolerance (WNIN/GR-Ob). However, only a few (15-20%) WNIN/Ob and WNIN/GR-Ob rats develop cataracts spontaneously with age. To gain further insights, we investigated the susceptibility of eye lens proteins of these obese rat strains to heat- and UV-induced aggregation in vitro, lens opacification upon glucose-mediated sorbitol accumulation ex vivo, and onset and progression of cataract was followed by galactose feeding and streptozotocin (STZ) injection. The results indicated increased susceptibility toward heat- or UV-induced aggregation of lens proteins in obese animals compared to their littermate lean controls. Further, in organ culture studies glucose-induced sorbitol accumulation was found to be higher and thus the lens opacification was faster in obese animals compared to their lean littermates. Also, the onset and progression of galactose- or STZ-induced cataractogenesis was faster in obese animals compared to lean control. These results together with our previous observations suggest that obesity status could lead to hyperaccumulation of sorbitol in eye lens, predisposing them to cataract, primarily by increasing their susceptibility to environmental and/or physiological factors. Further, intralenticular sorbitol accumulation beyond a threshold level could lead to cataract in WNIN/Ob and WNIN/GR-Ob rats.
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Small molecule kaempferol modulates PDX-1 protein expression and subsequently promotes pancreatic β-cell survival and function via CREB. J Nutr Biochem 2012; 24:638-46. [PMID: 22819546 DOI: 10.1016/j.jnutbio.2012.03.008] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2011] [Revised: 02/21/2012] [Accepted: 03/01/2012] [Indexed: 01/09/2023]
Abstract
Chronic hyperlipidemia causes β-cell apoptosis and dysfunction, thereby contributing to the pathogenesis of type 2 diabetes (T2D). Thus, searching for agents to promote pancreatic β-cell survival and improve its function could be a promising strategy to prevent and treat T2D. We investigated the effects of kaempferol, a small molecule isolated from ginkgo biloba, on apoptosis and function of β-cells and further determined the mechanism underlying its actions. Kaempferol treatment promoted viability, inhibited apoptosis and reduced caspase-3 activity in INS-1E cells and human islets chronically exposed to palmitate. In addition, kaempferol prevented the lipotoxicity-induced down-regulation of antiapoptotic proteins Akt and Bcl-2. The cytoprotective effects of kaempferol were associated with improved insulin secretion, synthesis, and pancreatic and duodenal homeobox-1 (PDX-1) expression. Chronic hyperlipidemia significantly diminished cyclic adenosine monophosphate (cAMP) production, protein kinase A (PKA) activation, cAMP-responsive element binding protein (CREB) phosphorylation and its regulated transcriptional activity in β-cells, all of which were restored by kaempferol treatment. Disruption of CREB expression by transfection of CREB siRNA in INS-1E cells or adenoviral transfer of dominant-negative forms of CREB in human islets ablated kaempferol protection of β-cell apoptosis and dysfunction caused by palmitate. Incubation of INS-1E cells or human islets with kaempferol for 48h induced PDX-1 expression. This effect of kaempferol on PDX-1 expression was not shared by a host of structurally related flavonoid compounds. PDX-1 gene knockdown reduced kaempferol-stimulated cAMP generation and CREB activation in INS-1E cells. These findings demonstrate that kaempferol is a novel survivor factor for pancreatic β-cells via up-regulating the PDX-1/cAMP/PKA/CREB signaling cascade.
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Lu ZQ, Sun WH, Yan J, Jiang TX, Zhai SN, Li Y. Cigarette smoking, body mass index associated with the risks of age-related cataract in male patients in northeast China. Int J Ophthalmol 2012; 5:317-22. [PMID: 22773980 DOI: 10.3980/j.issn.2222-3959.2012.03.13] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2012] [Accepted: 05/10/2012] [Indexed: 11/02/2022] Open
Abstract
AIM To determine the association between cigarettes smoking, body mass index (BMI) and the risk of age-related cataract (ARC) in middle-aged and elderly men in Northeast China. METHODS A hospital-based case control study was conducted. Cases (n =362) were men who had surgically treated ARC, 45-85 years old; controls frequency-matched (n =362) were men who had been admitted to the same hospital as cases for other diseases not related with eye diseases. Cases and controls were matched with 1:1. The cases and controls were interviewed during their hospital stay, using a structured interviewer-administrated questionnaire that included information on sociodemographic characteristics, socioeconomic, lifestyle habits (tobacco smoking and alcohol consumption, etc.), anthropometric measures, personal medical history, and family history of ARC in first-degree relatives, and simultaneously BMI was calculated. The odds ratios (OR) and 95% confidence intervals (CI) of ARC were estimated using multiple logistic regression models. RESULTS After adjusting for age and multiple potential confounders, higher BMI was associated with an increased risk of ARC. Cigarette smoking, years smoking or moderate cigarette smoking (1-29 cigarettes per day) had no relation with the risk of ARC (P>0.05), although patients smoking ≥30 cigarettes per day had an elevated risk of ARC as compared with the non-smokers (OR=1.55, 95% CI; 1.16-2.85, P=0.026). Higher BMI was associated with an increased risk of ARC. Both overweight and obesity was associated with an obviously increased risk for surgically ARC (OR=1.55, 95% CI: 1.02-1.98, P=0.015 and OR=1.71, 95% CI: 1.32-2.39, P=0.013 respectively) compared to normal BMI. Then participants were grouped into quartiles of BMI (Q1 to Q4), compared to controls in the lowest quartile, the OR for cases in the highest quartile of BMI was 1.54 (OR=1.54, 95% CI: 1.08-2.46, P=0.022). The results of univariate analysis showed cigarette smoking was not associated with ARC formation for men with lower or normal BMI (P>0.05). Compared to the non-smokers, for men of overweight or obesity, cigarette smoking was associated with a significantly increased risk for surgically ARC (OR=2.00, 95% CI: 1.49-6.65, P=0.003 and OR=1.66, 95% CI: 1.63-13.21, P=0.002 respectively). Similarly, smokers in the highest quartile of BMI had approximately 1.5 times the risk of ARC as non-smokers in the lowest quartile (OR=1.46, 95% CI: 1.06-5.29, P<0.001). Followed multivariate models revealed that the association had never changed. CONCLUSION Current cigarette smoking is positively related to ARC only among those who smoking 30 or more cigarettes per day. For men who are both overweight and obesity, cigarette smoking is associated with a significantly increased risk for ARC.
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Affiliation(s)
- Zhi-Quan Lu
- Department of Epidemiology, Liaoning Medical University, Jinzhou 121001, Liaoning Province, China
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Choi KH, Park MS, Kim JT, Chang J, Nam TS, Choi SM, Lee SH, Kim BC, Kim MK, Cho KH. Serum triglyceride level is an important predictor of early prognosis in patients with acute ischemic stroke. J Neurol Sci 2012; 319:111-6. [PMID: 22578636 DOI: 10.1016/j.jns.2012.04.018] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2012] [Revised: 04/18/2012] [Accepted: 04/18/2012] [Indexed: 01/09/2023]
Abstract
BACKGROUND Some recent studies have shown that poor outcomes after acute ischemic stroke (AIS) were closely related to lower serum triglyceride (TG) levels, not hypertriglyceridemia. However, hypertriglyceridemia has been shown to be an independent predictor for poor outcome in patients with coronary artery disease. This study attempted to evaluate the association between serum TG levels and early prognosis of AIS. METHODS We enrolled 736 consecutive patients with AIS. Based on the TG level, patients were divided into 5 groups based on the guidelines of the National Cholesterol Education Program (NCEP). We defined early neurological deterioration (END) as a 4-point or greater deterioration of the NIH stroke scale (NIHSS) score and early clinical improvement (ECI) as a 4-point reduction of NIHSS within a week after symptom onset. We compared patients with END, ECI, and neither END nor ECI. RESULTS The risk of END was significantly higher in the hyperTG and hypoTG groups compared with the normal group. The percentages of ECI were significantly lower in the hypoTG, borderline, and hyperTG groups compared with the normal group. For END, the multivariable adjusted odds ratios were significantly higher in the hypoTG, borderline, and hyperTG groups compared with the low normal group (50 to 100mg/dl). CONCLUSIONS TG had a nonlinear, J-shaped association with poor outcome and a reverse J-shaped association with good outcome in AIS. This study suggests that both hyperTG and hypoTG can be risk factors for poor early outcome in AIS.
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Affiliation(s)
- Kang-Ho Choi
- Department of Neurology, Cerebrovascular Center, Chonnam National University Hospital, Gwangju, South Korea
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Monickaraj F, Aravind S, Gokulakrishnan K, Sathishkumar C, Prabu P, Prabu D, Mohan V, Balasubramanyam M. Accelerated aging as evidenced by increased telomere shortening and mitochondrial DNA depletion in patients with type 2 diabetes. Mol Cell Biochem 2012; 365:343-50. [PMID: 22411737 DOI: 10.1007/s11010-012-1276-0] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2011] [Accepted: 02/24/2012] [Indexed: 12/13/2022]
Abstract
Although shortened telomeres were shown associated with several risk factors of diabetes, there is lack of data on their relationship with mitochondrial dysfunction. Therefore, we compared the relationship between telomere length and mitochondrial DNA (mtDNA) content in patients with type 2 diabetes mellitus (T2DM; n = 145) and in subjects with normal glucose tolerance (NGT; n = 145). Subjects were randomly recruited from the Chennai Urban Rural Epidemiology Study. mtDNA content and telomere length were assessed by Real-Time PCR. Malonodialdehyde, a marker of lipid peroxidation was measured by thiobarbituric acid reactive substances (TBARS) using fluorescence methodology. Adiponectin levels were measured by radioimmunoassay. Oxidative stress as determined by lipid peroxidation (TBARS) was significantly (p < 0.001) higher in patients with T2DM compared to NGT subjects. In contrast, the mean telomere length, adiponectin and mtDNA content were significantly (p < 0.001) lower in patients with T2DM compared to NGT subjects. Telomere length was positively correlated with adiponectin, HDL, mtDNA content and good glycemic/lipid control and negatively correlated with adiposity and insulin resistance. On regression analysis, shortened telomeres showed significant association with T2DM even after adjusting for waist circumference, insulin resistance, triglyceride, HDL, adiponectin, mtDNA & TBARS. mtDNA depletion showed significant association with T2DM after adjusting for waist circumference and adiponectin but lost its significance when further adjusted for telomere length, TBARS and insulin resistance. Our study emphasizes the clustering of accelerated aging features viz., shortened telomeres, decreased mtDNA content, hypoadiponectinemia, low HDL, and increased oxidative stress in Asian Indian type 2 diabetes patients.
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Affiliation(s)
- Finny Monickaraj
- Department of Cell and Molecular Biology, Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention and Control, IDF Centre of Education, Gopalapuram, Chennai 600 086, Tamilnadu, India
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Fabrizi F, Martin P, Dixit V, Messa P. Hepatitis C virus infection and kidney disease: a meta-analysis. Clin J Am Soc Nephrol 2012; 7:549-57. [PMID: 22403269 DOI: 10.2215/cjn.06920711] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND OBJECTIVES Hepatitis C virus (HCV) infection and kidney disease are both highly prevalent diseases. The association between HCV and GN has been supported by previous research but little is known about the relationship between HCV and kidney disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A systematic review of the published medical literature was conducted to determine if HCV is associated with increased likelihood of kidney disease in the general population. A random-effects model was used to generate a summary estimate of the relative risk for kidney disease, defined as an estimated GFR <60 ml/min per 1.73 m(2) or proteinuria, with HCV across the published studies. RESULTS Nine clinical studies (817,917 unique individuals) were identified. Pooling of study results demonstrated the absence of a relationship between HCV seropositive status and reduced estimated GFR (adjusted relative risk, 1.12; 95% confidence interval, 0.91, 1.38; P=0.28) according to the random-effects model. HCV seropositive serology was an independent and significant risk factor for proteinuria (defined by urine dipstick test or spot urine albumin/creatinine ratio) in the general population, with a summary estimate for adjusted relative risk of 1.47 (95% confidence interval, 1.12, 1.94; P=0.006). Significant heterogeneity was observed between studies (Ri=0.82; P value by Q test, <0.001). CONCLUSIONS This meta-analysis shows that HCV is independently associated with proteinuria but not with reduced GFR in the general population. Substantial heterogeneity occurred.
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Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology and Dialysis, Maggiore Policlinico Hospital, IRCCS Foundation, Milan, Italy.
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Cagnone GLM, Dufort I, Vigneault C, Sirard MA. Differential gene expression profile in bovine blastocysts resulting from hyperglycemia exposure during early cleavage stages. Biol Reprod 2012; 86:50. [PMID: 22075474 DOI: 10.1095/biolreprod.111.094391] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
To understand the compromised survival of embryos derived from assisted reproductive techniques, transcriptome survey of early embryonic development has shown the impact of in vitro culture environment on gene expression in bovine or other living species. However, how the differentially expressed genes translate into developmentally compromised embryos is unresolved. We therefore aimed to characterize transcriptomic markers expressed by bovine blastocysts cultured in conditions that are known to impair embryo development. As increasing glucose concentrations has been shown to be stressful for early cleavage stages of mammalian embryos and to decrease subsequent blastocyst survival, in vitro-matured/fertilized bovine zygotes were cultured in control (0.2 mM) or high-glucose (5 mM) conditions until the 8- to 16-cell stage, and then transferred to control media until they reached the blastocyst stage. The concentration of 5 mM glucose was chosen as a stress treatment because there was a significant effect on blastocyst rate without the treatment's being lethal as with 10 mM. Microarray analysis revealed gene expression differences unrelated to embryo sex or hatching. Overrepresented processes among differentially expressed genes in treated blastocysts were extracellular matrix signalling, calcium signaling, and energy metabolism. On a pathophysiological level, higher glucose treatment impacts pathways associated with diabetes and tumorigenesis through genes controlling the Warburg effect, i.e., emphasis on use of anaerobic glycolysis rather than oxidative phosphorylation. These results allowed us to conclude that disruption of in vitro preattachment development is concomitant with gene expression modifications involved in metabolic control.
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Affiliation(s)
- Gaël L M Cagnone
- Département des Sciences Animales, Centre de Recherche en Biologie de la Reproduction, Université Laval, Québec, Canada
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Peng CH, Chyau CC, Chan KC, Chan TH, Wang CJ, Huang CN. Hibiscus sabdariffa polyphenolic extract inhibits hyperglycemia, hyperlipidemia, and glycation-oxidative stress while improving insulin resistance. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2011; 59:9901-9909. [PMID: 21870884 DOI: 10.1021/jf2022379] [Citation(s) in RCA: 82] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
H. sabdariffa polyphenolic extract (HPE) was demonstrated to inhibit high glucose-stimulated cellular changes. In this study, we analyzed the composition of HPE and used a type 2 diabetic rat model to test its protective effect. At least 18 phenolic compounds were found in HPE. Treatment with HPE reduced hyperglycemia and hyperinsulinemia, especially at the dose of 200 mg/kg. HPE decreased serum triacylglycerol, cholesterol, and the ratio of low density lipoprotein/high density lipoprotein (LDL/HDL). Diabetes promoted plasma advanced glycation end product (AGE) formation and lipid peroxidation, while HPE significantly reduced these elevations. Immunohistological observation revealed that HPE inhibited the expression of connective tissue growth factor (CTGF) and receptor of AGE (RAGE), which was increased in type 2 diabetic aortic regions. Furthermore, HPE recovered the weight loss found in type 2 diabetic rats. In conclusion, we demonstrated the anti-insulin resistance properties of HPE and its effect on hypoglycemia, hypolipidemia, and antioxidation. HPE has the potential to be an adjuvant for diabetic therapy.
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Affiliation(s)
- Chiung-Huei Peng
- Division of Basic Medical Science and Institute of Biotechnology, Hungkuang University, and Department of Internal Medicine, Chung Shan Medical University Hospital, Number 34, Chung Chie Road, Shalu County, Taichung 433, Taiwan
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Lee SD, Ju G, Choi JA, Kim JW, Yoon IY. The association of oxidative stress with central obesity in obstructive sleep apnea. Sleep Breath 2011; 16:511-7. [PMID: 21614576 DOI: 10.1007/s11325-011-0536-7] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2011] [Revised: 05/04/2011] [Accepted: 05/11/2011] [Indexed: 11/30/2022]
Abstract
PURPOSE The purpose of this paper is to evaluate concentrations of multiple oxidative stress and antioxidant status markers in patients with obstructive sleep apnea (OSA) and normal controls of comparable obesity. METHODS A total of 73 male subjects, recruited from a sleep clinic or advertisements, were enrolled in this study. All subjects underwent overnight polysomnography. The subjects were divided into normal control (n = 20), mild to moderate OSA (n = 31), and severe OSA (n = 22) with no difference in obesity. Blood was withdrawn from subjects, and markers of oxidative stress and antioxidant status, and parameters of glucose metabolism were assessed. RESULTS There was no significant difference in either oxidative stress or antioxidant status markers among the three groups. There was no significant correlation between the oxidative stress markers and the OSA variables. However, there were correlations between waist-to-hip ratio (WHR)-oxidized low-density lipoprotein cholesterol (oxLDL) (r = 0.424), WHR-glutathione peroxidase (GPX) (r = 0.318), WHR-total antioxidant status (TAS) (r = -0.317), and WHR-superoxide dismutase (SOD) (r = -0.338). In multiple regression analysis, WHR was a significant independent variable of oxLDL, GPX, TAS, and SOD. CONCLUSIONS The oxidative stress in OSA was related to central obesity rather than intermittent hypoxia or respiratory disturbances. To control cardiovascular complications in OSA, weight reduction should be a component in the treatment strategy.
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Affiliation(s)
- Sang Don Lee
- Department of Neuropsychiatry, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, South Korea
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Yoshino T, Nakae I, Matsumoto T, Mitsunami K, Horie M. Association between brachial-ankle pulse wave velocity and endothelium-dependent and -independent coronary vasomotor function. Clin Exp Pharmacol Physiol 2010; 38:34-41. [DOI: 10.1111/j.1440-1681.2010.05455.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Rubel R, Dalla Santa HS, Fernandes LC, Bonatto SJR, Bello S, Figueiredo BC, Lima Filho JHC, Santos CAM, Soccol CR. Hypolipidemic and antioxidant properties of Ganoderma lucidum (Leyss:Fr) Karst used as a dietary supplement. World J Microbiol Biotechnol 2010. [DOI: 10.1007/s11274-010-0554-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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