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Yeo RX, Mau T, Ross ZM, Edenhoffer NP, Liu J, Barnes HN, Lui LY, Adkins JN, Sanford JA, Seldin MM, Viesi CH, Zhou M, Gregory HL, Toledo FGS, Stefanovic-Racic M, Lyles M, Wood AN, Mattila PE, Blakley EA, Miljkovic I, Cawthon PM, Newman AB, Kritchevsky SB, Cummings SR, Goodpaster BH, Justice JN, Kershaw EE, Sparks LM. Investigating the role of adipose tissue in mobility and aging: design and methods of the Adipose Tissue ancillary to the Study of Muscle, Mobility, and Aging (SOMMA-AT). J Gerontol A Biol Sci Med Sci 2025; 80:glaf015. [PMID: 39886989 DOI: 10.1093/gerona/glaf015] [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: 05/22/2024] [Indexed: 02/01/2025] Open
Abstract
BACKGROUND Age-related changes in adipose tissue affect chronic medical diseases and mobility disability but mechanism remains poorly understood. The goal of this study is to define methods for phenotyping unique characteristics of adipose tissue from older adults. METHODS Older adults enrolled in study of muscle, mobility, and aging selected for the adipose tissue ancillary (SOMMA-AT; N = 210, 52.38% women, 76.12 ± 4.37 years) were assessed for regional adiposity by whole-body magnetic resonance (AMRA) and underwent a needle-aspiration biopsy of abdominal subcutaneous adipose tissue (ASAT). ASAT biopsies were flash frozen, fixed, or processed for downstream applications and deposited at the biorepository. Biopsy yields, qualitative features, adipocyte sizes, and concentration of adipokines secreted in ASAT explant conditioned media were measured. Inter-measure Spearman correlations were determined. RESULTS Regional, but not total, adiposity differed by sex: women had greater ASAT mass (8.20 ± 2.73 kg, p < .001) and biopsy yield (3.44 ± 1.81 g, p < .001) than men (ASAT = 5.95 ± 2.30 kg, biopsy = 2.30 ± 1.40 g). ASAT mass correlated with leptin (r = 0.54, p < .001) and not resistin (p = .248) and adiponectin (p = .353). Adipocyte area correlated with ASAT mass (r = 0.34, p < .001), BMI (r = 0.33, p < .001), adiponectin (r = -0.22, p = .005) and leptin (r = 0.18, p = .024) but not with resistin (p = .490). CONCLUSION In addition to the detailed ASAT biopsy processing in this report, we found that adipocyte area correlated with ASAT mass, and both measures related to some key adipokines in the explant conditioned media. These results, methods, and biological repositories underscore the potential of this unique cohort to impact the understanding of aging adipose biology on disease, disability, and other aging tissues.
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Affiliation(s)
- Reichelle X Yeo
- AdventHealth Translational Research Institute, Orlando, Florida, USA
| | - Theresa Mau
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA
- Department of Epidemiology, San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, California, USA
| | - Zana M Ross
- Department of Medicine, Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Nicholas P Edenhoffer
- Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Jingfang Liu
- Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Haley N Barnes
- Department of Epidemiology, San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, California, USA
| | - Li-Yung Lui
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA
- Department of Epidemiology, San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, California, USA
| | - Joshua N Adkins
- Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA
| | - James A Sanford
- Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA
| | - Marcus M Seldin
- Department of Biological Chemistry, University of California, Irvine, Irvine, California, USA
| | - Carlos H Viesi
- Department of Biological Chemistry, University of California, Irvine, Irvine, California, USA
| | - Mingqi Zhou
- Department of Biological Chemistry, University of California, Irvine, Irvine, California, USA
| | - Heather L Gregory
- Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Frederico G S Toledo
- Department of Medicine, Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Maja Stefanovic-Racic
- Department of Medicine, Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Mary Lyles
- Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Ashlee N Wood
- Department of Medicine, Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Polly E Mattila
- Department of Medicine, Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | | | - Iva Miljkovic
- Department of Medicine, Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Peggy M Cawthon
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA
- Department of Epidemiology, San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, California, USA
| | - Anne B Newman
- Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Stephen B Kritchevsky
- Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Steven R Cummings
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA
- Department of Epidemiology, San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, California, USA
| | - Bret H Goodpaster
- AdventHealth Translational Research Institute, Orlando, Florida, USA
| | - Jamie N Justice
- Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
- XPRIZE Foundation, Culver City, California, USA
| | - Erin E Kershaw
- Department of Medicine, Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Lauren M Sparks
- AdventHealth Translational Research Institute, Orlando, Florida, USA
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Zhu J, Hou Y, Yu W, Wang J, Chu X, Zhang X, Pang H, Ma D, Tang Y, Li M, Yuan C, Xie J, Wang C, Zhang J. Adipose tissue-derived microRNA-450a-5p induces type 2 diabetes mellitus by downregulating DUSP10. MOLECULAR BIOMEDICINE 2025; 6:7. [PMID: 39912972 PMCID: PMC11803021 DOI: 10.1186/s43556-025-00247-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 01/11/2025] [Accepted: 01/17/2025] [Indexed: 02/07/2025] Open
Abstract
Type 2 diabetes mellitus (T2DM) has rapidly increased worldwide, emerging as the fifth leading cause of death. The treatment of T2DM is challenging due to the side effects of oral hypoglycemic drugs and the limited efficacy of long-term insulin therapy, which can lead to insulin resistance (IR). Consequently, there is significant in discovering new drugs that have minimal side effects and a pronounced hypoglycemic effect. In obesity, microRNA levels have been implicated in glucose metabolism disorders and T2DM, although many aspects remain unresolved. Here, we confirmed that visceral adipose tissue and serum microRNA-450a-5p content increased under obesity and T2DM, and it was significantly positively associated with fasting blood glucose, triglycerides, cholesterol, low-density lipoproteins-cholesterol levels of the subjects. In high-fat diet (HFD)-induced obese mice, microRNA-450a-5p expression was increased in the serum, liver, and white adipose tissue. Moreover, the adipose Dicer-knockout mouse model was constructed to identify adipose tissue as the main source of microRNA-450a-5p. microRNA-450a-5p could inactivate the insulin signal pathway by targeting the inhibited Dual Specificity Phosphatase 10 (DUSP10) and inducing IR and glucose metabolism disorders in vitro cultured hepatocytes and adipocytes. Additionally, microRNA-450a-5p was found to regulate DUSP10 expression and insulin signaling activity, influencing glucose tolerance and insulin sensitivity across various models, including normal diet, HFD-induced obese, adipose tissue-specific microRNA-450a-5p-knockout, and db/db mice. Furthermore, gallic acid might play a potential role in inhibiting glucose levels by decreasing microRNA-450a-5p expression. Thus, microRNA-450a-5p emerges as an attractive therapeutic target for addressing obesity, IR, and T2DM.
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Affiliation(s)
- Jiaojiao Zhu
- Medical College of Shihezi University, Bei-Er-Lu, Shihezi, Xinjiang, 832000, China
| | - Yanting Hou
- Medical College of Shihezi University, Bei-Er-Lu, Shihezi, Xinjiang, 832000, China
| | - Wei Yu
- School of Pharmacy, Xinjiang Shihezi University, Xinjiang, 832002, China
| | - Jingzhou Wang
- Medical College of Shihezi University, Bei-Er-Lu, Shihezi, Xinjiang, 832000, China
| | - Xiaolong Chu
- Medical College of Shihezi University, Bei-Er-Lu, Shihezi, Xinjiang, 832000, China
| | - Xueting Zhang
- Medical College of Shihezi University, Bei-Er-Lu, Shihezi, Xinjiang, 832000, China
| | - Huai Pang
- Medical College of Shihezi University, Bei-Er-Lu, Shihezi, Xinjiang, 832000, China
| | - Dingling Ma
- Medical College of Shihezi University, Bei-Er-Lu, Shihezi, Xinjiang, 832000, China
| | - Yihan Tang
- Medical College of Shihezi University, Bei-Er-Lu, Shihezi, Xinjiang, 832000, China
| | - Menghuan Li
- Medical College of Shihezi University, Bei-Er-Lu, Shihezi, Xinjiang, 832000, China
| | - Chenggang Yuan
- Medical College of Shihezi University, Bei-Er-Lu, Shihezi, Xinjiang, 832000, China
| | - Jianxin Xie
- Medical College of Shihezi University, Bei-Er-Lu, Shihezi, Xinjiang, 832000, China.
| | - Cuizhe Wang
- Medical College of Shihezi University, Bei-Er-Lu, Shihezi, Xinjiang, 832000, China.
| | - Jun Zhang
- Medical College of Shihezi University, Bei-Er-Lu, Shihezi, Xinjiang, 832000, China.
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Souza-Tavares H, Miranda CS, Vasques-Monteiro IML, Sandoval C, Santana-Oliveira DA, Silva-Veiga FM, Fernandes-da-Silva A, Souza-Mello V. Peroxisome proliferator-activated receptors as targets to treat metabolic diseases: Focus on the adipose tissue, liver, and pancreas. World J Gastroenterol 2023; 29:4136-4155. [PMID: 37475842 PMCID: PMC10354577 DOI: 10.3748/wjg.v29.i26.4136] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 05/26/2023] [Accepted: 06/13/2023] [Indexed: 07/10/2023] Open
Abstract
The world is experiencing reflections of the intersection of two pandemics: Obesity and coronavirus disease 2019. The prevalence of obesity has tripled since 1975 worldwide, representing substantial public health costs due to its comorbidities. The adipose tissue is the initial site of obesity impairments. During excessive energy intake, it undergoes hyperplasia and hypertrophy until overt inflammation and insulin resistance turn adipocytes into dysfunctional cells that send lipotoxic signals to other organs. The pancreas is one of the organs most affected by obesity. Once lipotoxicity becomes chronic, there is an increase in insulin secretion by pancreatic beta cells, a surrogate for type 2 diabetes mellitus (T2DM). These alterations threaten the survival of the pancreatic islets, which tend to become dysfunctional, reaching exhaustion in the long term. As for the liver, lipotoxicity favors lipogenesis and impairs beta-oxidation, resulting in hepatic steatosis. This silent disease affects around 30% of the worldwide population and can evolve into end-stage liver disease. Although therapy for hepatic steatosis remains to be defined, peroxisome proliferator-activated receptors (PPARs) activation copes with T2DM management. Peroxisome PPARs are transcription factors found at the intersection of several metabolic pathways, leading to insulin resistance relief, improved thermogenesis, and expressive hepatic steatosis mitigation by increasing mitochondrial beta-oxidation. This review aimed to update the potential of PPAR agonists as targets to treat metabolic diseases, focusing on adipose tissue plasticity and hepatic and pancreatic remodeling.
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Affiliation(s)
| | | | | | - Cristian Sandoval
- Escuela de Tecnología Médica, Facultad de Salud, Universidad Santo Tomás, Osorno 5310431, Chile
- Departamento de Ciencias Preclínicas, Universidad de la Frontera, Temuco 4780000, Chile
| | | | | | | | - Vanessa Souza-Mello
- Department of Anatomy, Rio de Janeiro State University, Rio de Janeiro 20551030, Brazil
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Sinha S, Haque M. Obesity, Diabetes Mellitus, and Vascular Impediment as Consequences of Excess Processed Food Consumption. Cureus 2022; 14:e28762. [PMID: 36105908 PMCID: PMC9441778 DOI: 10.7759/cureus.28762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/03/2022] [Indexed: 12/15/2022] Open
Abstract
Regular intake of ready-to-eat meals is related to obesity and several noninfectious illnesses, such as cardiovascular diseases, hypertension, diabetes mellitus (DM), and tumors. Processed foods contain high calories and are often enhanced with excess refined sugar, saturated and trans fat, Na+ andphosphate-containing taste enhancers, and preservatives. Studies showed that monosodium glutamate (MSG) induces raised echelons of oxidative stress, and excessive hepatic lipogenesis is concomitant to obesity and type 2 diabetes mellitus (T2DM). Likewise, more than standard salt intake adversely affects the cardiovascular system, renal system, and central nervous system (CNS), especially the brain. Globally, excessive utilization of phosphate-containing preservatives and additives contributes unswervingly to excessive phosphate intake through food. In addition, communities and even health experts, including medical doctors, are not well-informed about the adverse effects of phosphate preservatives on human health. Dietary phosphate excess often leads to phosphate toxicity, ultimately potentiating kidney disease development. The mechanisms involved in phosphate-related adverse effects are not explainable. Study reports suggested that high blood level of phosphate causes vascular ossification through the deposition of Ca2+ and substantially alters fibroblast growth factor-23 (FGF23) and calcitriol.
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Molecular Biological and Clinical Understanding of the Statin Residual Cardiovascular Disease Risk and Peroxisome Proliferator-Activated Receptor Alpha Agonists and Ezetimibe for Its Treatment. Int J Mol Sci 2022; 23:ijms23073418. [PMID: 35408799 PMCID: PMC8998547 DOI: 10.3390/ijms23073418] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/11/2022] [Accepted: 03/17/2022] [Indexed: 12/20/2022] Open
Abstract
Several randomized, double blind, placebo-controlled trials (RCTs) have demonstrated that low-density lipoprotein cholesterol (LDL-C) lowering by using statins, including high-doses of strong statins, reduced the development of cardiovascular disease (CVD). However, among the eight RCTs which investigated the effect of statins vs. placebos on the development of CVD, 56-79% of patients had the residual CVD risk after the trials. In three RCTs which investigated the effect of a high dose vs. a usual dose of statins on the development of CVD, 78-87% of patients in the high-dose statin arms still had the CVD residual risk after the trials. An analysis of the characteristics of patients in the RCTs suggests that elevated triglyceride (TG) and reduced high-density lipoprotein cholesterol (HDL-C), the existence of obesity/insulin resistance, and diabetes may be important metabolic factors which determine the statin residual CVD risk. To understand the association between lipid abnormalities and the development of atherosclerosis, we show the profile of lipoproteins and their normal metabolism, and the molecular and biological mechanisms for the development of atherosclerosis by high TG and/or low HDL-C in insulin resistance. The molecular biological mechanisms for the statin residual CVD risk include an increase of atherogenic lipoproteins such as small dense LDL and remnants, vascular injury and remodeling by inflammatory cytokines, and disturbed reverse cholesterol transport. Peroxisome proliferator-activated receptor alpha (PPARα) agonists improve atherogenic lipoproteins, reverse the cholesterol transport system, and also have vascular protective effects, such as an anti-inflammatory effect and the reduction of the oxidative state. Ezetimibe, an inhibitor of intestinal cholesterol absorption, also improves TG and HDL-C, and reduces intestinal cholesterol absorption and serum plant sterols, which are increased by statins and are atherogenic, possibly contributing to reduce the statin residual CVD risk.
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Khateeb S, Albalawi A, Alkhedaide A. Diosgenin Modulates Oxidative Stress and Inflammation in High-Fat Diet-Induced Obesity in Mice. Diabetes Metab Syndr Obes 2022; 15:1589-1596. [PMID: 35637860 PMCID: PMC9147404 DOI: 10.2147/dmso.s355677] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Accepted: 05/17/2022] [Indexed: 12/04/2022] Open
Abstract
INTRODUCTION Obesity is a chronic metabolic disorder that results in excessive energy accumulated in adipose tissue causing dysfunction of adipocytes, inflammation, and oxidative stress. Diosgenin (DG), a steroidal saponin produced by several plants, has been reported to have antioxidant activity. This study aimed to evaluate the effects of diosgenin on oxidative stress and inflammation in mice fed with a high-fat diet (HFD). METHODS Thirty adult male mice were divided into three groups including the control group, mice fed with a normal diet; the HFD group, mice fed with a high-fat diet for 6 weeks; and the HFD+DG group, mice fed with a high-fat diet and diosgenin daily for 6 weeks. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), and total antioxidant capacity (TAC) activities were evaluated. Histopathological changes in the adipose tissues have been investigated. RESULTS Data showed that diosgenin increased TAC activities with a concomitant decrease in MDA levels. As well, DG reduces the TNF and IL-6 levels. The histopathological changes in the adipose tissues due to high-fat consumption were restored upon DG supplementation. CONCLUSION Our results suggested that diosgenin is a promising agent for regulating obesity by increasing the levels of antioxidants, modifying oxidative stress and pro-inflammatory cytokines, which might prevent the onset of many diseases.
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Affiliation(s)
- Sahar Khateeb
- Biochemistry Division, Department of Chemistry, Faculty of Science, Fayoum University, Fayoum, Egypt
| | - Aishah Albalawi
- Biology Department, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia
| | - Adel Alkhedaide
- Department of Medical Laboratory, Turabah University College, Taif University, Taif, 21944, Saudi Arabia
- Correspondence: Adel Alkhedaide, Department of Medical Laboratory, Turabah University College, Taif University, P. O. Box 11099, Taif, 21944, Saudi Arabia, Tel +966540490404, Fax +966128224366, Email
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Hooshmand Moghadam B, Bagheri R, Ghanavati M, Khodadadi F, Cheraghloo N, Wong A, Nordvall M, Suzuki K, Shabkhiz F. The Combined Effects of 6 Weeks of Jump Rope Interval Exercise and Dark Chocolate Consumption on Antioxidant Markers in Obese Adolescent Boys. Antioxidants (Basel) 2021; 10:1675. [PMID: 34829546 PMCID: PMC8614646 DOI: 10.3390/antiox10111675] [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: 09/21/2021] [Revised: 10/13/2021] [Accepted: 10/22/2021] [Indexed: 11/25/2022] Open
Abstract
Research has shown that both dark chocolate and exercise training may have favorable effects on antioxidant function in obese cohorts. However, their combined effect has not been established. We assessed the influences of six weeks of dark chocolate consumption combined with jump rope exercise on antioxidant markers in adolescent boys with obesity. Fifty adolescent boys with obesity (age = 15 ± 1 years) were randomly assigned into one of four groups; jump rope exercise + white chocolate consumption (JW; n = 13), jump rope exercise + dark chocolate consumption (JD; n = 13), dark chocolate consumption (DC; n = 12), or control (C; n = 12). Two participants dropped out of the study. Participants in JW and JD groups performed jump rope exercise three times per week for six weeks. Participants in the DC and JD groups consumed 30 g of dark chocolate containing 83% of cocoa during the same period. Serum concentrations of superoxide dismutase (SOD), total antioxidant capacity (TAC), glutathione peroxidase (GPx), and thiobarbituric acid reactive substances (TBARS) were evaluated prior to and after the interventions. All 3 intervention groups noted significant (p < 0.01) increases in serum concentrations of TAC, SOD, and GPx from baseline to post-test. In contrast, all intervention groups showed significantly reduced serum concentrations of TBARS from pre- to post-test (p ≤ 0.01). Bonferroni post hoc analysis revealed that post-test serum concentrations of TAC in the JD group were significantly greater than C (p < 0.001), DC (p = 0.010), and JW (p < 0.001) groups. In addition, post-test serum concentrations of SOD in the JD group were significantly greater than C group (p = 0.001). Post-test serum concentrations of GPx in the JD group were significantly greater than C (p < 0.001), DC (p = 0.021), and JW (p = 0.032) groups. The post-test serum concentrations of TBARS in the JD group was significantly lower than C (p < 0.001). No other significant between-group differences were observed. The current study provides evidence that dark chocolate consumption in combination with jump rope exercise is more efficient in improving antioxidant capacity than dark chocolate consumption or jump rope exercise alone among obese adolescent boys.
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Affiliation(s)
- Babak Hooshmand Moghadam
- Department of Exercise Physiology, Ferdowsi University of Mashhad, Mashhad 9177948974, Iran; (B.H.M.); (F.K.)
- Department of Exercise Physiology, University of Tehran, Tehran 1961733114, Iran
| | - Reza Bagheri
- Department of Exercise Physiology, University of Isfahan, Isfahan 8174673441, Iran;
| | - Matin Ghanavati
- National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran 1416753955, Iran;
| | - Fatemeh Khodadadi
- Department of Exercise Physiology, Ferdowsi University of Mashhad, Mashhad 9177948974, Iran; (B.H.M.); (F.K.)
| | - Neda Cheraghloo
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran 1417613151, Iran;
| | - Alexei Wong
- Department of Health and Human Performance, Marymount University, Arlington, VA 22207, USA; (A.W.); (M.N.)
| | - Michael Nordvall
- Department of Health and Human Performance, Marymount University, Arlington, VA 22207, USA; (A.W.); (M.N.)
| | - Katsuhiko Suzuki
- Faculty of Sport Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa 359-1192, Japan
| | - Fatemeh Shabkhiz
- Department of Exercise Physiology, Ferdowsi University of Mashhad, Mashhad 9177948974, Iran; (B.H.M.); (F.K.)
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Higher Physical Activity Level Improves Leptin Concentrations in Spinal Cord Injury Subjects. BIOMED RESEARCH INTERNATIONAL 2021; 2021:9415253. [PMID: 34621899 PMCID: PMC8492252 DOI: 10.1155/2021/9415253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 08/10/2021] [Accepted: 09/09/2021] [Indexed: 11/26/2022]
Abstract
The present study was designed to compare the body composition and indicators of chronic inflammatory grade, such as leptin, adiponectin, and resistin concentrations in irregularly active and active SCI subjects. Thirty-two male subjects participated in this study. They were divided into three groups: able-bodied control irregularly active (control, n = 11), irregularly active with SCI (SCI-IA, n = 8), and physically active with SCI (SCI-PA, n = 13). The enzyme-linked immunosorbent assay (ELISA) assessed serum concentrations of leptin, adiponectin, and resistin. All volunteers performed the maximum oxygen uptake (VO2max) test, 24 h total energy expenditure (TEE), and body composition by skinfold thicknesses. Leptin concentrations were higher in the SCI-IA group when compared to the other groups, while no significant differences were found between the SCI-PA and control cohorts. In addition, no significant differences were found among groups for serum adiponectin and resistin concentrations either. The SCI-PA group showed significantly higher values for TEE and VO2max when compared to the other groups. Percentages of body fat and circumference were decreased in the control and SCI-PA groups when compared to the SCI-IA cohort. Associations between leptin and cardiorespiratory capacity and anthropometric markers were also observed. Our findings highlight that the lack of physical activity in the SCI subjects leads to poor general physical fitness and higher levels of body adiposity, which may induce hyperleptinemia, an essential marker for cardiometabolic disorders.
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Schöttker B, Gào X, Jansen EHJM, Brenner H. Associations of Human Colorectal Adenoma with Serum Biomarkers of Body Iron Stores, Inflammation and Antioxidant Protein Thiols. Antioxidants (Basel) 2021; 10:1195. [PMID: 34439443 PMCID: PMC8388983 DOI: 10.3390/antiox10081195] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 07/19/2021] [Accepted: 07/20/2021] [Indexed: 12/12/2022] Open
Abstract
Red and processed meat consumption and obesity are established risk factors for colorectal adenoma (CRA). Adverse changes in biomarkers of body iron stores (total serum iron, ferritin, transferrin and transferrin saturation), inflammation (high-sensitivity C-reactive protein [hs-CRP]) and anti-oxidative capacity (total of thiol groups (-S-H) of proteins [SHP]) might reflect underlying mechanisms that could explain the association of red/processed meat consumption and obesity with CRA. Overall, 100 CRA cases (including 71 advanced cases) and 100 CRA-free controls were frequency-matched on age and sex and were selected from a colonoscopy screening cohort. Odds ratios (OR) and 95% confidence intervals (95%CI) for comparisons of top and bottom biomarker tertiles were derived from multivariable logistic regression models. Ferritin levels were significantly positively associated with red/processed meat consumption and hs-CRP levels with obesity. SHP levels were significantly inversely associated with obesity. Transferrin saturation was strongly positively associated with overall and advanced CRA (ORs [95%CIs]: 3.05 [1.30-7.19] and 2.71 [1.03-7.13], respectively). Due to the high correlation with transferrin saturation, results for total serum iron concentration were similar (but not statistically significant). Furthermore, SHP concentration was significantly inversely associated with advanced CRA (OR [95%CI]: 0.29 [0.10-0.84]) but not with overall CRA (OR [95%CI]: 0.65 [0.27-1.56]). Ferritin, transferrin, and hs-CRP levels were not associated with CRA. High transferrin saturation as a sign of iron overload and a low SHP concentration as a sign of redox imbalance in obese patients might reflect underlying mechanisms that could in part explain the associations of iron overload and obesity with CRA.
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Affiliation(s)
- Ben Schöttker
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, 69120 Heidelberg, Germany; (X.G.); (H.B.)
- Network Aging Research, Heidelberg University, 69115 Heidelberg, Germany
| | - Xīn Gào
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, 69120 Heidelberg, Germany; (X.G.); (H.B.)
- Network Aging Research, Heidelberg University, 69115 Heidelberg, Germany
| | - Eugène HJM Jansen
- Centre for Health Protection, National Institute of Public Health and the Environment, 3721 MA Bilthoven, The Netherlands;
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, 69120 Heidelberg, Germany; (X.G.); (H.B.)
- Network Aging Research, Heidelberg University, 69115 Heidelberg, Germany
- Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center, 69120 Heidelberg, Germany
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Zehravi M, Maqbool M, Ara I. Correlation between obesity, gestational diabetes mellitus, and pregnancy outcomes: an overview. Int J Adolesc Med Health 2021; 33:339-345. [PMID: 34142511 DOI: 10.1515/ijamh-2021-0058] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 05/09/2021] [Indexed: 11/15/2022]
Abstract
Obesity has been identified mainly as a raise in the body's adiposity leading to prolonged overshoot of caloric intake over expenditure. Obesity has significant health-altering implications which have been shown to be implicated in the pathogenesis and progression of other diseases through its extensive physiological assaults. The prevalence of overweight and obesity has been an increasing epidemic worldwide. The number of obese births was even on the increase, with an increasing number of women of reproductive age registering as obese. Obesity is related to adverse perinatal outcomes and increased morbidity and mortality in pregnant women. The potential risk for multiple antenatal, postpartum, intrapartum, and neonatal complications is maternal obesity. Greater risk of developing Gestational Diabetes Mellitus (GDM), pregnancy induced hypertension (PIH), pre-eclampsia, risk of venous embolism, increased need for labor induction, and cesarean sections in the mother have been recorded in a comprehensive analysis of pregnancy complications associated with obesity. The link between obesity, gestational diabetes, and pregnancy outcomes will be briefly shown in this article.
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Affiliation(s)
- Mehrukh Zehravi
- Department of Clinical Pharmacy Girls Section, Prince Sattam Bin Abdul Aziz University, Alkharj, Saudia Arabia
| | - Mudasir Maqbool
- Department of Pharmaceutical Sciences, University of Kashmir, Srinagar, Jammu and Kashmir, India
| | - Irfat Ara
- Regional Research Institute of Unani Medicine, Srinagar, Jammu and Kashmir, India
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11
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Nery M, Ferreira PS, Gonçalves DR, Spolidorio LC, Manthey JA, Cesar TB. Physiological effects of tangeretin and heptamethoxyflavone on obese C57BL/6J mice fed a high-fat diet and analyses of the metabolites originating from these two polymethoxylated flavones. Food Sci Nutr 2021; 9:1997-2009. [PMID: 33841818 PMCID: PMC8020949 DOI: 10.1002/fsn3.2167] [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: 09/16/2020] [Revised: 11/28/2020] [Accepted: 01/17/2021] [Indexed: 12/29/2022] Open
Abstract
Two compounds from citrus peel, tangeretin (TAN) and 3',4',3,5,6,7,8-heptamethoxyflavone (HMF), were investigated for their abilities to repair metabolic damages caused by an high-fat diet (HFD) in C57BL/6J mice. In the first 4 weeks, mice were fed either a standard diet (11% kcal from fat) for the control group, or a HFD (45% kcal from fat) to establish obesity in three experimental groups. In the following 4 weeks, two groups receiving the HFD were supplemented with either TAN or HMF at daily doses of 100 mg/kg body weight, while the two remaining groups continued to receive the standard healthy diet or the nonsupplemented HFD. Four weeks of supplementation with TAN and HMF resulted in intermediate levels of blood serum glucose, leptin, resistin, and insulin resistance compared with the healthy control and the nonsupplemented HFD groups. Blood serum peroxidation (TBARS) levels were significantly lower in the TAN and HMF groups compared with the nonsupplemented HFD group. Several differences occurred in the physiological effects of HMF versus TAN. TAN, but not HMF, reduced adipocyte size in the mice with pre-existent obesity, while HMF, but not TAN, decreased fat accumulation in the liver and also significantly increased the levels of an anti-inflammatory cytokine, IL-10. In an analysis of the metabolites of TAN and HMF, several main classes occurred, including a new set of methylglucuronide conjugates. It is suggested that contrasts between the observed physiological effects of TAN and HMF may be attributable to the differences in numbers and chemical structures of TAN and HMF metabolites.
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Affiliation(s)
- Marina Nery
- Department of Food and NutritionLaboratory of NutritionFaculty of Pharmaceutical SciencesSão Paulo State University (UNESP)AraraquaraBrazil
| | - Paula S. Ferreira
- Department of Food and NutritionLaboratory of NutritionFaculty of Pharmaceutical SciencesSão Paulo State University (UNESP)AraraquaraBrazil
- U.S. Horticultural Research LaboratoryAgricultural Research ServiceUSDAFort PierceFLUSA
| | - Danielle R. Gonçalves
- Department of Food and NutritionLaboratory of NutritionFaculty of Pharmaceutical SciencesSão Paulo State University (UNESP)AraraquaraBrazil
- U.S. Horticultural Research LaboratoryAgricultural Research ServiceUSDAFort PierceFLUSA
| | - Luis C. Spolidorio
- Department of Physiology and PathologySchool of DentistrySão Paulo State University (UNESP)AraraquaraBrazil
| | - John A. Manthey
- U.S. Horticultural Research LaboratoryAgricultural Research ServiceUSDAFort PierceFLUSA
| | - Thais B. Cesar
- Department of Food and NutritionLaboratory of NutritionFaculty of Pharmaceutical SciencesSão Paulo State University (UNESP)AraraquaraBrazil
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12
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Muller CR, Williams AT, Eaker AM, Dos Santos F, Palmer AF, Cabrales P. High fat high sucrose diet-induced dyslipidemia in guinea pigs. J Appl Physiol (1985) 2021; 130:1226-1234. [PMID: 33703947 DOI: 10.1152/japplphysiol.00013.2021] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Easy access to high-calorie and fat-dense fast food has resulted in unhealthy dietary and lifestyle changes worldwide, which affects both developed and developing economies. This predisposes populations to a considerable number of metabolic and inflammatory conditions, such as diabetes, nonalcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD). Guinea pigs have been proposed as a model to study high-fat diet-induced metabolic disease due to their similar antioxidant metabolism and lipid profile to humans, and their susceptibility to atherosclerosis and endothelial disease. This study aims to evaluate cardiovascular and metabolic disorders induced by high-fat high-sucrose diet (HFHSD) in guinea pigs. Two to three-week-old male guinea pigs were fed a normal diet (ND) or HFHSD for 12 wk. Guinea pigs fed a HFHSD developed glucose intolerance, dyslipidemia, and liver, cardiac, and kidney damage. However, hypertension, dysautonomia, endothelial disease, and obesity were absent in these HFHSD guinea pigs. Taken together, these results show that guinea pigs fed a HFHSD are a nonobese model of metabolic disorders, resulting in important cardiac damage. Moreover, our findings suggest that NAFLD may be an important risk factor for diet-induced CVD.NEW & NOTEWORTHY In this study, we show a new animal model for diet-induced disease metabolic disorders without obesity in guinea pigs. Moreover, results suggest a strong relation between liver disease and increased cardiovascular risks.
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Affiliation(s)
- Cynthia R Muller
- Department of Bioengineering, University of California San Diego, California
| | | | - Allyn M Eaker
- Department of Bioengineering, University of California San Diego, California
| | - Fernando Dos Santos
- Department of Anesthesiology & Critical Care, University of California San Diego, California
| | - Andre F Palmer
- William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio
| | - Pedro Cabrales
- Department of Bioengineering, University of California San Diego, California
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13
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Zhu J, Wang C, Zhang X, Qiu T, Ma Y, Li X, Pang H, Xiong J, Yang X, Pan C, Xie J, Zhang J. Correlation analysis of microribonucleic acid-155 and microribonucleic acid-29 with type 2 diabetes mellitus, and the prediction and verification of target genes. J Diabetes Investig 2021; 12:165-175. [PMID: 32579760 PMCID: PMC7858142 DOI: 10.1111/jdi.13334] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 06/13/2020] [Accepted: 06/18/2020] [Indexed: 12/25/2022] Open
Abstract
AIMS/INTRODUCTION Microribonucleic acid-155 (microRNA155) and microRNA29 are reported to inhibit glucose metabolism in some cell and animal models, but no evidence from susceptible populations that examines the relationship between microRNA155 or microRNA29 and type 2 diabetes mellitus currently exists. Furthermore, target genes regulated by microRNA155 and microRNA29 that affect glucose and lipid metabolism remain unknown. MATERIALS AND METHODS Human participants were divided into normal weight (n = 72), obesity (n = 120) and type 2 diabetes (n = 59) groups. The contents of microRNA155 and microRNA29 abundance in serum were measured, and candidate genes potentially related to glucose and lipid metabolism targeted by either microRNA155 or microRNA29 were screened. Overexpression of microRNA155 and microRNA29 in HepG2 cells was used to verify candidate gene expression, and measure the effects on glucose and lipid metabolism. RESULTS Serum levels of microRNA155 and microRNA29 show a significant increase in individuals with obesity and type 2 diabetes compared with normal weight individuals. Identified target genes for microRNA155 were MAPK14, MAP3K10, DUSP14 and PRKAR2B. Identified target genes for microRNA29 were PEX11A and FADS1. Overexpression of microRNA155 or microRNA29 in HepG2 cells was found to downregulate the expression of identified target genes, and result in inhibition of triglyceride synthesis and glucose incorporation. CONCLUSIONS MicroRNA155 and microRNA29 were significantly higher in type 2 diabetes patients compared with the control patients, their levels were also positively correlated with fasting plasma glucose levels, and over-expression of microRNA155 or microRNA29 were found to downregulate glucose and lipid metabolism target genes, and reduce lipid synthesis and glucose incorporation in HepG2 cells.
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Affiliation(s)
- Jiaojiao Zhu
- Department of Biochemistry and Molecular BiologyShihezi University School of MedicineShiheziXinjiangChina
| | - Cuizhe Wang
- Shihezi University School of MedicineShiheziXinjiangChina
| | - Xueting Zhang
- Department of Biochemistry and Molecular BiologyShihezi University School of MedicineShiheziXinjiangChina
| | - Tongtong Qiu
- Department of Biochemistry and Molecular BiologyShihezi University School of MedicineShiheziXinjiangChina
| | - Yinghua Ma
- Department of Biochemistry and Molecular BiologyShihezi University School of MedicineShiheziXinjiangChina
| | - Xue Li
- Department of Biochemistry and Molecular BiologyShihezi University School of MedicineShiheziXinjiangChina
| | - Huai Pang
- Department of Biochemistry and Molecular BiologyShihezi University School of MedicineShiheziXinjiangChina
| | - Jianyu Xiong
- Department of Biochemistry and Molecular BiologyShihezi University School of MedicineShiheziXinjiangChina
| | - Xin Yang
- Department of Biochemistry and Molecular BiologyShihezi University School of MedicineShiheziXinjiangChina
| | - Chongge Pan
- Department of Biochemistry and Molecular BiologyShihezi University School of MedicineShiheziXinjiangChina
| | - Jianxin Xie
- Department of Biochemistry and Molecular BiologyShihezi University School of MedicineShiheziXinjiangChina
| | - Jun Zhang
- Ministry of Education Key Laboratory of Xinjiang Endemic and Ethnic DiseaseShiheziXinjiangChina
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14
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Čolak E, Pap D. The role of oxidative stress in the development of obesity and obesity-related metabolic disorders. J Med Biochem 2021; 40:1-9. [PMID: 33584134 PMCID: PMC7857849 DOI: 10.5937/jomb0-24652] [Citation(s) in RCA: 78] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Accepted: 01/30/2020] [Indexed: 12/21/2022] Open
Abstract
Obesity is a serious medical condition, defined as excessive accumulation of fat. Abdominal fat is recognized as the major risk for obesity related diseases such as: hypertension, dyslipidemia, type 2 diabetes mellitus, coronary heart disease, stroke, non-alcoholic fatty liver disease etc. Fat accumulation is also related to pro-oxidant and pro-inflammatory states. Recently published articles suggest that oxidative stress may be a link between obesity and related complications. Adiposity leads to increased oxidative stress via several multiple biochemical processes such as superoxide generation through the action of NADPH oxidase, glyceraldehyde auto-oxidation, oxidative phosphorylation, protein kinase C (PKC) activation, and polyol and hexosamine pathways. On the other hand, oxidative stress plays a causative role in the development of obesity, by stimulating the deposition of adipose tissue, including preadipocyte proliferation, adipocyte differentiation and growth. Exercise-induced weight loss can improve the redox state by modulating both oxidative stress and antioxidant promoters, which reduce endothelial dysfunction and inflammation.
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Affiliation(s)
- Emina Čolak
- Clinical Center of Serbia, Institute of Medical Biochemistry, Department for Scientific Research and Education, Belgrade
| | - Dragana Pap
- Students Health Protection Institute, Department of Laboratory Diagnostics, Novi Sad
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15
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Fantin F, Disegna E, Manzato G, Comellato G, Zoico E, Rossi AP, Mazzali G, Rajkumar C, Zamboni M. Adipokines and Arterial Stiffness in the Elderly. Vasc Health Risk Manag 2020; 16:535-543. [PMID: 33324067 PMCID: PMC7733384 DOI: 10.2147/vhrm.s274861] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 11/18/2020] [Indexed: 12/27/2022] Open
Abstract
INTRODUCTION The aim of this study was to evaluate the relationship between adipokines and arterial stiffness in a group of 85 elderly subjects and the role of leptin and adiponectin on subclinical vascular damage, defined by a PWV>10 m/s. METHODS In each subject, we evaluated anthropometry, body composition by DXA (fat mass, fat mass%, lean mass), metabolic variables, leptin, adiponectin, systolic, diastolic, mean arterial pressure and pulse pressure (SBP, DBP, MAP, PP), carotid-femoral pulse wave velocity (cfPWV) and carotid-radial pulse wave velocity (crPWV). RESULTS In the study population, significant associations were observed between cfPWV and crPWV, age, SBP, MAP, waist circumference, fat body mass and leptin. The study population was subdivided in 2 subgroups according to adipokine patterns: group 1 included patients with high adiponectin and low leptin, and group 2 patients had high leptin and low adiponectin. SBP, PP, cfPWV were significantly higher in subjects with high leptin and low adiponectin (group 2). Even after adjustment for gender, fat mass%, MAP, HDL cholesterol and triglycerides, cfPWV was higher in group 2 than group 1. In a logistic binary regression on the entire population, considering subclinical vascular damage as a dependent variable and age, gender, MAP, fat mass%, triglycerides, HDL cholesterol and category of subjects with high leptin and low adiponectin as independent variables, MAP and category of subjects with high leptin and low adiponectin were significant predictors (OR, respectively, 1.09 and 3.61). CONCLUSION In conclusion, in the elderly, the presence at the same time of high leptin levels and low adiponectin levels seems to have synergic effects on arterial stiffness.
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Affiliation(s)
- Francesco Fantin
- Department of Medicine, Section of Geriatrics Medicine, University of Verona, Verona, Italy
| | - Eleonora Disegna
- Department of Medicine, Section of Geriatrics Medicine, University of Verona, Verona, Italy
| | - Gisella Manzato
- Department of Medicine, Section of Geriatrics Medicine, University of Verona, Verona, Italy
| | - Gabriele Comellato
- Department of Medicine, Section of Geriatrics Medicine, University of Verona, Verona, Italy
| | - Elena Zoico
- Department of Medicine, Section of Geriatrics Medicine, University of Verona, Verona, Italy
| | - Andrea P Rossi
- Department of Medicine, Section of Geriatrics Medicine, University of Verona, Verona, Italy
| | - Gloria Mazzali
- Department of Medicine, Section of Geriatrics Medicine, University of Verona, Verona, Italy
| | | | - Mauro Zamboni
- Department of Surgery, Dentistry, Paediatrics and Gynaecology, Section of Geriatrics, University of Verona, Verona, Italy
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16
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Xie ZJ, Novograd J, Itzkowitz Y, Sher A, Buchen YD, Sodhi K, Abraham NG, Shapiro JI. The Pivotal Role of Adipocyte-Na K peptide in Reversing Systemic Inflammation in Obesity and COVID-19 in the Development of Heart Failure. Antioxidants (Basel) 2020; 9:E1129. [PMID: 33202598 PMCID: PMC7697697 DOI: 10.3390/antiox9111129] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 11/11/2020] [Accepted: 11/11/2020] [Indexed: 01/10/2023] Open
Abstract
This review summarizes data from several laboratories that have demonstrated a role of the Na/K-ATPase, specifically its α1 subunit, in the generation of reactive oxygen species (ROS) via the negative regulator of Src. Together with Src and other signaling proteins, the Na/K-ATPase forms an oxidant amplification loop (NKAL), amplifies ROS, and participates in cytokines storm in obesity. The development of a peptide fragment of the α1 subunit, NaKtide, has been shown to negatively regulate Src. Several groups showed that the systemic administration of the cell permeable modification of NaKtide (pNaKtide) or its selective delivery to fat tissue-adipocyte specific expression of NaKtide-ameliorate the systemic elevation of inflammatory cytokines seen in chronic obesity. Severe acute respiratory syndrome - coronavirus 2 (SARS-CoV-2), the RNA Coronavirus responsible for the COVID-19 global pandemic, invades cells via the angiotensin converting enzyme 2 (ACE-2) receptor (ACE2R) that is appended in inflamed fat tissue and exacerbates the formation of the cytokines storm. Both obesity and heart and renal failure are well known risks for adverse outcomes in patients infected with COVID-19. White adipocytes express ACE-2 receptors in high concentration, especially in obese patients. Once the virus invades the white adipocyte cell, it creates a COVID19-porphyrin complex which degrades and produces free porphyrin and iron and increases ROS. The increased formation of ROS and activation of the NKAL results in a further potentiated formation of ROS production, and ultimately, adipocyte generation of more inflammatory mediators, leading to systemic cytokines storm and heart failure. Moreover, chronic obesity also results in the reduction of antioxidant genes such as heme oxygenase-1 (HO-1), increasing adipocyte susceptibility to ROS and cytokines. It is the systemic inflammation and cytokine storm which is responsible for many of the adverse outcomes seen with COVID-19 infections in obese subjects, leading to heart failure and death. This review will also describe the potential antioxidant drugs and role of NaKtide and their demonstrated antioxidant effect used as a major strategy for improving obesity and epicardial fat mediated heart failure in the context of the COVID pandemic.
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Affiliation(s)
- Zi-jian Xie
- Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA; (Z.-j.X.); (K.S.)
| | - Joel Novograd
- Department of Medicine, New York Medical College, Valhalla, NY 10595, USA; (J.N.); (Y.I.); (A.S.); (Y.D.B.)
| | - Yaakov Itzkowitz
- Department of Medicine, New York Medical College, Valhalla, NY 10595, USA; (J.N.); (Y.I.); (A.S.); (Y.D.B.)
| | - Ariel Sher
- Department of Medicine, New York Medical College, Valhalla, NY 10595, USA; (J.N.); (Y.I.); (A.S.); (Y.D.B.)
| | - Yosef D. Buchen
- Department of Medicine, New York Medical College, Valhalla, NY 10595, USA; (J.N.); (Y.I.); (A.S.); (Y.D.B.)
| | - Komal Sodhi
- Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA; (Z.-j.X.); (K.S.)
| | - Nader G. Abraham
- Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA; (Z.-j.X.); (K.S.)
- Department of Medicine, New York Medical College, Valhalla, NY 10595, USA; (J.N.); (Y.I.); (A.S.); (Y.D.B.)
| | - Joseph I. Shapiro
- Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA; (Z.-j.X.); (K.S.)
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17
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Paus R, Ramot Y, Kirsner RS, Tomic-Canic M. Topical L-thyroxine: The Cinderella among hormones waiting to dance on the floor of dermatological therapy? Exp Dermatol 2020; 29:910-923. [PMID: 32682336 PMCID: PMC7722149 DOI: 10.1111/exd.14156] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 06/28/2020] [Accepted: 07/13/2020] [Indexed: 12/15/2022]
Abstract
Topical hormone therapy with natural or synthetic ligands of nuclear hormone receptors such as glucocorticoids, vitamin D analogues and retinoids has a long and highly successful tradition in dermatology. Yet the dermatological potential of thyroid hormone receptor (TR) agonists has been widely ignored, despite abundant clinical, cell and molecular biology, mouse in vivo, and human skin and hair follicle organ culture data documenting a role of TR-mediated signalling in skin physiology and pathology. Here, we review this evidence, with emphasis on wound healing and hair growth, and specifically highlight the therapeutic potential of repurposing topical L-thyroxine (T4) for selected applications in future dermatological therapy. We underscore the known systemic safety and efficacy profile of T4 in clinical medicine, and the well-documented impact of thyroid hormones on, for example, human epidermal and hair follicle physiology, hair follicle epithelial stem cells and pigmentation, keratin expression, mitochondrial energy metabolism and wound healing. On this background, we argue that short-term topical T4 treatment deserves careful further preclinical and clinical exploration for repurposing as a low-cost, effective and widely available dermatotherapeutic, namely in the management of skin ulcers and telogen effluvium, and that its predictable adverse effects are well-manageable.
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Affiliation(s)
- Ralf Paus
- Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
- Centre for Dermatology Research, University of Manchester & NIHR Manchester Biomedical Research Centre, Manchester, UK
- Monasterium Laboratory, Münster, Germany
| | - Yuval Ramot
- Department of Dermatology, Hadassah Medical Center, The Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Robert S. Kirsner
- Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Marjana Tomic-Canic
- Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
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18
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Martínez-Sánchez N. There and Back Again: Leptin Actions in White Adipose Tissue. Int J Mol Sci 2020; 21:ijms21176039. [PMID: 32839413 PMCID: PMC7503240 DOI: 10.3390/ijms21176039] [Citation(s) in RCA: 75] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 08/17/2020] [Accepted: 08/18/2020] [Indexed: 12/13/2022] Open
Abstract
Leptin is a hormone discovered almost 30 years ago with important implications in metabolism. It is primarily produced by white adipose tissue (WAT) in proportion to the amount of fat. The discovery of leptin was a turning point for two principle reasons: on one hand, it generated promising expectations for the treatment of the obesity, and on the other, it changed the classical concept that white adipose tissue was simply an inert storage organ. Thus, adipocytes in WAT produce the majority of leptin and, although its primary role is the regulation of fat stores by controlling lipolysis and lipogenesis, this hormone also has implications in other physiological processes within WAT, such as apoptosis, browning and inflammation. Although a massive number of questions related to leptin actions have been answered, the necessity for further clarification facilitates constantly renewing interest in this hormone and its pathways. In this review, leptin actions in white adipose tissue will be summarized in the context of obesity.
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19
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Tun S, Spainhower CJ, Cottrill CL, Lakhani HV, Pillai SS, Dilip A, Chaudhry H, Shapiro JI, Sodhi K. Therapeutic Efficacy of Antioxidants in Ameliorating Obesity Phenotype and Associated Comorbidities. Front Pharmacol 2020; 11:1234. [PMID: 32903449 PMCID: PMC7438597 DOI: 10.3389/fphar.2020.01234] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 07/28/2020] [Indexed: 12/13/2022] Open
Abstract
Obesity has been a worldwide epidemic for decades. Despite the abundant increase in knowledge regarding the etiology and pathogenesis of obesity, the prevalence continues to rise with estimates predicting considerably higher numbers by the year 2030. Obesity is characterized by an abnormal lipid accumulation, however, the physiological consequences of obesity are far more concerning. The development of the obesity phenotype constitutes dramatic alterations in adipocytes, along with several other cellular mechanisms which causes substantial increase in systemic oxidative stress mediated by reactive oxygen species (ROS). These alterations promote a chronic state of inflammation in the body caused by the redox imbalance. Together, the systemic oxidative stress and chronic inflammation plays a vital role in maintaining the obese state and exacerbating onset of cardiovascular complications, Type II diabetes mellitus, dyslipidemia, non-alcoholic steatohepatitis, and other conditions where obesity has been linked as a significant risk factor. Because of the apparent role of oxidative stress in the pathogenesis of obesity, there has been a growing interest in attenuating the pro-oxidant state in obesity. Hence, this review aims to highlight the therapeutic role of antioxidants, agents that negate pro-oxidant state of cells, in ameliorating obesity and associated comorbidities. More specifically, this review will explore how various antioxidants target unique and diverse pathways to exhibit an antioxidant defense mechanism.
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Affiliation(s)
- Steven Tun
- Departments of Medicine, Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, Huntington, WV, United States
| | - Caleb James Spainhower
- Departments of Medicine, Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, Huntington, WV, United States
| | - Cameron Lee Cottrill
- Departments of Medicine, Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, Huntington, WV, United States
| | - Hari Vishal Lakhani
- Departments of Medicine, Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, Huntington, WV, United States
| | - Sneha S Pillai
- Departments of Medicine, Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, Huntington, WV, United States
| | - Anum Dilip
- Departments of Medicine, Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, Huntington, WV, United States
| | - Hibba Chaudhry
- Departments of Medicine, Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, Huntington, WV, United States
| | - Joseph I Shapiro
- Departments of Medicine, Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, Huntington, WV, United States
| | - Komal Sodhi
- Departments of Medicine, Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, Huntington, WV, United States
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20
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Sindhu S, Akhter N, Wilson A, Thomas R, Arefanian H, Al Madhoun A, Al-Mulla F, Ahmad R. MIP-1α Expression Induced by Co-Stimulation of Human Monocytic Cells with Palmitate and TNF-α Involves the TLR4-IRF3 Pathway and Is Amplified by Oxidative Stress. Cells 2020; 9:1799. [PMID: 32751118 PMCID: PMC7465096 DOI: 10.3390/cells9081799] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 07/20/2020] [Accepted: 07/27/2020] [Indexed: 12/19/2022] Open
Abstract
Metabolic inflammation is associated with increased expression of saturated free fatty acids, proinflammatory cytokines, chemokines, and adipose oxidative stress. Macrophage inflammatory protein (MIP)-1α recruits the inflammatory cells such as monocytes, macrophages, and neutrophils in the adipose tissue; however, the mechanisms promoting the MIP-1α expression remain unclear. We hypothesized that MIP-1α co-induced by palmitate and tumor necrosis factor (TNF)-α in monocytic cells/macrophages could be further enhanced in the presence of reactive oxygen species (ROS)-mediated oxidative stress. To investigate this, THP-1 monocytic cells and primary human macrophages were co-stimulated with palmitate and TNF-α and mRNA and protein levels of MIP-1α were measured by using quantitative reverse transcription, polymerase chain reaction (qRT-PCR) and commercial enzyme-linked immunosorbent assays (ELISA), respectively. The cognate receptor of palmitate, toll-like receptor (TLR)-4, was blunted by genetic ablation, neutralization, and chemical inhibition. The involvement of TLR4-downstream pathways, interferon regulatory factor (IRF)-3 or myeloid differentiation (MyD)-88 factor, was determined using IRF3-siRNA or MyD88-deficient cells. Oxidative stress was induced in cells by hydrogen peroxide (H2O2) treatment and ROS induction was measured by dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. The data show that MIP-1α gene/protein expression was upregulated in cells co-stimulated with palmitate/TNF-α compared to those stimulated with either palmitate or TNF-α (P < 0.05). Further, TLR4-IRF3 pathway was implicated in the cooperative induction of MIP-1α in THP-1 cells, and this cooperativity between palmitate and TNF-α was clathrin-dependent and also required signaling through c-Jun and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Notably, ROS itself induced MIP-1α and could further promote MIP-1α secretion together with palmitate and TNF-α. In conclusion, palmitate and TNF-α co-induce MIP-1α in human monocytic cells via the TLR4-IRF3 pathway and signaling involving c-Jun/NF-κB. Importantly, oxidative stress leads to ROS-driven MIP-1α amplification, which may have significance for metabolic inflammation.
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Affiliation(s)
- Sardar Sindhu
- Animal & Imaging Core Facility, Dasman Diabetes Institute (DDI), Al-Soor Street, P.O. Box 1180, Dasman 15462, Kuwait;
| | - Nadeem Akhter
- Immunology & Microbiology, Dasman Diabetes Institute (DDI), Al-Soor Street, P.O. Box 1180, Dasman 15462, Kuwait; (N.A.); (A.W.); (R.T.); (H.A.)
| | - Ajit Wilson
- Immunology & Microbiology, Dasman Diabetes Institute (DDI), Al-Soor Street, P.O. Box 1180, Dasman 15462, Kuwait; (N.A.); (A.W.); (R.T.); (H.A.)
| | - Reeby Thomas
- Immunology & Microbiology, Dasman Diabetes Institute (DDI), Al-Soor Street, P.O. Box 1180, Dasman 15462, Kuwait; (N.A.); (A.W.); (R.T.); (H.A.)
| | - Hossein Arefanian
- Immunology & Microbiology, Dasman Diabetes Institute (DDI), Al-Soor Street, P.O. Box 1180, Dasman 15462, Kuwait; (N.A.); (A.W.); (R.T.); (H.A.)
| | - Ashraf Al Madhoun
- Animal & Imaging Core Facility, Dasman Diabetes Institute (DDI), Al-Soor Street, P.O. Box 1180, Dasman 15462, Kuwait;
- Genetics & Bioinformatics, Dasman Diabetes Institute (DDI), Al-Soor Street, P.O. Box 1180, Dasman 15462, Kuwait;
| | - Fahd Al-Mulla
- Genetics & Bioinformatics, Dasman Diabetes Institute (DDI), Al-Soor Street, P.O. Box 1180, Dasman 15462, Kuwait;
| | - Rasheed Ahmad
- Immunology & Microbiology, Dasman Diabetes Institute (DDI), Al-Soor Street, P.O. Box 1180, Dasman 15462, Kuwait; (N.A.); (A.W.); (R.T.); (H.A.)
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Bojková B, Winklewski PJ, Wszedybyl-Winklewska M. Dietary Fat and Cancer-Which Is Good, Which Is Bad, and the Body of Evidence. Int J Mol Sci 2020; 21:ijms21114114. [PMID: 32526973 PMCID: PMC7312362 DOI: 10.3390/ijms21114114] [Citation(s) in RCA: 79] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 05/27/2020] [Accepted: 06/02/2020] [Indexed: 12/13/2022] Open
Abstract
A high-fat diet (HFD) induces changes in gut microbiota leading to activation of pro-inflammatory pathways, and obesity, as a consequence of overnutrition, exacerbates inflammation, a known risk factor not only for cancer. However, experimental data showed that the composition of dietary fat has a greater impact on the pathogenesis of cancer than the total fat content in isocaloric diets. Similarly, human studies did not prove that a decrease in total fat intake is an effective strategy to combat cancer. Saturated fat has long been considered as harmful, but the current consensus is that moderate intake of saturated fatty acids (SFAs), including palmitic acid (PA), does not pose a health risk within a balanced diet. In regard to monounsaturated fat, plant sources are recommended. The consumption of plant monounsaturated fatty acids (MUFAs), particularly from olive oil, has been associated with lower cancer risk. Similarly, the replacement of animal MUFAs with plant MUFAs decreased cancer mortality. The impact of polyunsaturated fatty acids (PUFAs) on cancer risk depends on the ratio between ω-6 and ω-3 PUFAs. In vivo data showed stimulatory effects of ω-6 PUFAs on tumour growth while ω-3 PUFAs were protective, but the results of human studies were not as promising as indicated in preclinical reports. As for trans FAs (TFAs), experimental data mostly showed opposite effects of industrially produced and natural TFAs, with the latter being protective against cancer progression, but human data are mixed, and no clear conclusion can be made. Further studies are warranted to establish the role of FAs in the control of cell growth in order to find an effective strategy for cancer prevention/treatment.
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Affiliation(s)
- Bianka Bojková
- Department of Animal Physiology, Institute of Biology and Ecology, Faculty of Science, P.J. Šafárik University in Košice, 041 54 Košice, Slovakia;
| | - Pawel J. Winklewski
- Department of Human Physiology, Medical University of Gdansk, 80-210 Gdansk, Poland;
- Department of Anatomy and Physiology, Pomeranian University of Slupsk, 76-200 Slupsk, Poland
- Correspondence: ; Tel./Fax: +48-58-3491515
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Cannabinoid Receptor Type 2: A Possible Target in SARS-CoV-2 (CoV-19) Infection? Int J Mol Sci 2020; 21:ijms21113809. [PMID: 32471272 PMCID: PMC7312493 DOI: 10.3390/ijms21113809] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 05/22/2020] [Accepted: 05/26/2020] [Indexed: 01/08/2023] Open
Abstract
In late December 2019, a novel coronavirus (SARS-CoV-2 or CoV-19) appeared in Wuhan, China, causing a global pandemic. SARS-CoV-2 causes mild to severe respiratory tract inflammation, often developing into lung fibrosis with thrombosis in pulmonary small vessels and causing even death. COronaVIrus Disease (COVID-19) patients manifest exacerbated inflammatory and immune responses, cytokine storm, prevalence of pro-inflammatory M1 macrophages and increased levels of resident and circulating immune cells. Men show higher susceptibility to SARS-CoV-2 infection than women, likely due to estrogens production. The protective role of estrogens, as well as an immune-suppressive activity that limits the excessive inflammation, can be mediated by cannabinoid receptor type 2 (CB2). The role of this receptor in modulating inflammation and immune response is well documented in fact in several settings. The stimulation of CB2 receptors is known to limit the release of pro-inflammatory cytokines, shift the macrophage phenotype towards the anti-inflammatory M2 type and enhance the immune-modulating properties of mesenchymal stromal cells. For these reasons, we hypothesize that CB2 receptor can be a therapeutic target in COVID-19 pandemic emergency.
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Sharath SS, Ramu J, Nair SV, Iyer S, Mony U, Rangasamy J. Human Adipose Tissue Derivatives as a Potent Native Biomaterial for Tissue Regenerative Therapies. Tissue Eng Regen Med 2020; 17:123-140. [PMID: 31953618 PMCID: PMC7105544 DOI: 10.1007/s13770-019-00230-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 11/07/2019] [Accepted: 11/15/2019] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Human adipose tissue is a great source of translatable biomaterials owing to its ease of availability and simple processing. Reusing discardable adipose tissue for tissue regeneration helps in mimicking the exact native microenvironment of tissue. Over the past 10 years, extraction, processing, tuning and fabrication of adipose tissue have grabbed the attention owing to their native therapeutic and regenerative potential. The present work gives the overview of next generation biomaterials derived from human adipose tissue and their development with clinical relevance. METHODS Around 300 articles have been reviewed to widen the knowledge on the isolation, characterization techniques and medical applications of human adipose tissue and its derivatives from bench to bedside. The prospective applications of adipose tissue derivatives like autologous fat graft, stromal vascular fraction, stem cells, preadipocyte, adipokines and extracellular matrix, their behavioural mechanism, rational property of providing native bioenvironment, circumventing their translational abilities, recent advances in featuring them clinically have been reviewed extensively to reveal the dormant side of human adipose tissue. RESULTS Basic understanding about the molecular and structural aspect of human adipose tissue is necessary to employ it constructively. This review has nailed the productive usage of human adipose tissue, in a stepwise manner from exploring the methods of extracting derivatives, concerns during processing and its formulations to turning them into functional biomaterials. Their performance as functional biomaterials for skin regeneration, wound healing, soft tissue defects, stem cell and other regenerative therapies under in vitro and in vivo conditions emphasizes the translational efficiency of adipose tissue derivatives. CONCLUSION In the recent years, research interest has inclination towards constructive tissue engineering and regenerative therapies. Unravelling the maximum utilization of human adipose tissue derivatives paves a way for improving existing tissue regeneration and cellular based therapies and other biomedical applications.
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Affiliation(s)
- Siva Sankari Sharath
- Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041, India
| | - Janarthanan Ramu
- Department of Plastic and Reconstructive Surgery, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041, India
| | - Shantikumar Vasudevan Nair
- Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041, India
| | - Subramaniya Iyer
- Department of Plastic and Reconstructive Surgery, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041, India
| | - Ullas Mony
- Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041, India.
| | - Jayakumar Rangasamy
- Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041, India.
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Gegin S, Celikel S, Celik D, Pazarli AC. Evaluation of Interleukin-6, Leukotriene B-4, and Nitric Oxide Levels in Exhaled Breath Condensate of Asymptomatic Obese Individuals: Are Obese Patients Under Risk of Developing Asthma? Eurasian J Med 2020; 52:25-28. [PMID: 32158309 DOI: 10.5152/eurasianjmed.2019.19181] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Objective If systemic inflammation in relation with obesity causes asthma, the detection of increased airway inflammation among obese individuals who do not have any respiratory symptoms can be also beneficial in indentifying obese patients who are at risk of developing asthma. The aim of this study was to evaluate the systemic and airway inflammation of asymptomatic obese and non-obese individuals. Materials and Methods Obese and non-obese individuals with no respiratory symptoms were included. Inflammatory biomarkers such as C-reactive protein (CRP), exhaled breath condensate (EBC) interleukin-6 (IL-6), EBC leukotriene B-4 (LTB-4), and EBC nitric oxide (NO) levels of obese and non-obese individuals were determined. Results Forty-five obese individuals (body mass index [BMI]≥30) and 31 non-obese individuals (BMI≤25) as a control group were included in this study. The mean age of the obese group (38.7±11.4 years) was significantly higher than the one of the non-obese group (29.5±8.6 years; p<0.001). There was no significant relationship between gender and BMI (χ2 =1.471, p=0.225). CRP levels were significantly higher in the obese group (6.94±8.28) than the non-obese group (3.29±0.39; p<0.001). The levels of EBC IL-6 in obese and non-obese group were found as 22.61±12.53 and 21.08±14.39, respectively (p=0.624). There was no significant difference between EBC NO levels of the obese group and non-obese group (24.35±10.9 vs. 21.56±7.83; p=0.226). No significant difference was found between the EBC LTB-4 level in the obese group and the non-obese group (36.39±89.82 vs. 16.64±17.45; p=0.231). Conclusion Increased systemic inflammation in obese individuals who had no respiratory symptoms might indicate the tendency of asthma. However, airway inflammation was not significantly different between groups. Therefore the relationship between obesity and asthma should be investigated in future large-scale studies determining the direct effects of adipokines on airways.
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Affiliation(s)
- Savas Gegin
- Department of Pulmonary Diseases, University of Health Sciences, Samsun Training and Research Hospital, Samsun, Turkey
| | - Serhat Celikel
- Department of Pulmonary Diseases, İstanbul Medipol University, İstanbul, Turkey
| | - Deniz Celik
- Department of Pulmonary Diseases and Thoracic Surgery, University of Health Sciences, Ankara Atatürk Training and Research Hospital, Ankara, Turkey
| | - Ahmet Cemal Pazarli
- Department of Pulmonary Diseases, Gaziosmanpaşa University School of Medicine, Tokat, Turkey
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Anusruti A, Xuan Y, Gào X, Jansen EHJM, Laetsch DC, Brenner H, Schöttker B. Factors associated with high oxidative stress in patients with type 2 diabetes: a meta-analysis of two cohort studies. BMJ Open Diabetes Res Care 2020; 8:8/1/e000933. [PMID: 32079612 PMCID: PMC7039603 DOI: 10.1136/bmjdrc-2019-000933] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 12/10/2019] [Accepted: 01/15/2020] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE Our objective is to identify the potential factors associated with serum Diacron's reactive oxygen metabolites test (D-ROM) levels of patients with type 2 diabetes mellitus (T2DM) by conducting cross-sectional and longitudinal analyses in two large cohorts and further strengthening these results by performing a meta-analysis. METHODS Serum D-ROM concentrations were measured in 1045 and 1101 patients with T2DM from two independent cohort studies from Germany at baseline and repeatedly 3-4 years later. The cross-sectional and longitudinal associations of various potential determinants with D-ROM levels were assessed with a backwards selection algorithm in multivariable adjusted models. RESULTS In the meta-analysis of the cross-sectional analysis, female sex, low education, obesity, smoking, high total cholesterol, hemoglobin A1c ≥7%, no diabetes medication, a history of myocardial infarction, heart failure, a history of cancer and C reactive protein levels (CRP) >3 mg/L were statistically significantly associated with increased D-ROM levels in patients with T2DM. The meta-analysis of the longitudinal analysis revealed that old age, female sex, obesity, smoking, physical inactivity, high alcohol consumption, ≥5 years since diabetes diagnosis and CRP levels between 3 mg/L and 10 mg/L were statistically significantly associated with D-ROM levels measured 3-4 years later. CONCLUSIONS VALIDITY, LIMITATIONS AND CLINICAL APPLICABILITY This comprehensive analysis confirmed that several modifiable risk factors are being associated with oxidative stress in patients with T2DM within an observational study design. We discuss potential prevention measures against these risk factors that might help to reduce oxidative stress and to prevent some cases of premature mortality in patients with T2DM.
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Affiliation(s)
- Ankita Anusruti
- Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Heidelberg, Germany
- Network Aging Research, University of Heidelberg, Heidelberg, Germany
| | - Yang Xuan
- Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Heidelberg, Germany
- Network Aging Research, University of Heidelberg, Heidelberg, Germany
| | - Xīn Gào
- Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Heidelberg, Germany
| | - Eugène H J M Jansen
- Centre for Health Protection, National Institute of Public Health and the Environment, Bilthoven, The Netherlands
| | - Dana Clarissa Laetsch
- Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Heidelberg, Germany
- Network Aging Research, University of Heidelberg, Heidelberg, Germany
| | - Ben Schöttker
- Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Heidelberg, Germany
- Network Aging Research, University of Heidelberg, Heidelberg, Germany
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Anusruti A, Jansen EHJM, Gào X, Xuan Y, Brenner H, Schöttker B. Longitudinal Associations of Body Mass Index, Waist Circumference, and Waist-to-Hip Ratio with Biomarkers of Oxidative Stress in Older Adults: Results of a Large Cohort Study. Obes Facts 2020; 13:66-76. [PMID: 31986512 PMCID: PMC7098284 DOI: 10.1159/000504711] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 11/10/2019] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND In the literature, obesity is discussed as a determinant of high oxidative stress (OS). Hence, prevention or reduction of obesity could prevent high OS and subsequently serve as a target for "healthy aging." METHODS Diacron's reactive oxygen metabolites test (D-ROM) and total thiol levels (TTL), a marker of antioxidant defense capacity, were measured in 1,734 participants of a population-based cohort study of older adults (age range: 57-83 years) at 2 time points 3 years apart. The longitudinal associations of body mass index, waist-to-hip ratio, and waist circumference with D-ROM and TTL were assessed with multivariable adjusted generalized linear models. Dose-response analyses were conducted with restricted cubic splines. RESULTS D-ROM was not significantly associated with any of the weight measures. On the contrary, TTL showed statistically significant, inverse linear associations with all weight measures. CONCLUSION A healthy body weight seems to be highly relevant for the antioxidative defense capacity of human beings. In contrast, D-ROM levels were independent of the study participant's weight. Clinical trials are needed to corroborate if loss of weight by obese individuals can effectively increase TTL and subsequently also life expectancy.
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Affiliation(s)
- Ankita Anusruti
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Network Aging Research, Heidelberg University, Heidelberg, Germany
| | - Eugène H J M Jansen
- Center for Health Protection, National Institute of Public Health and the Environment, Bilthoven, The Netherlands
| | - Xīn Gào
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Network Aging Research, Heidelberg University, Heidelberg, Germany
| | - Yang Xuan
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Network Aging Research, Heidelberg University, Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Network Aging Research, Heidelberg University, Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Ben Schöttker
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany,
- Network Aging Research, Heidelberg University, Heidelberg, Germany,
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Alsaggar M, Bdour S, Ababneh Q, El-Elimat T, Qinna N, Alzoubi KH. Silibinin attenuates adipose tissue inflammation and reverses obesity and its complications in diet-induced obesity model in mice. BMC Pharmacol Toxicol 2020; 21:8. [PMID: 31973745 PMCID: PMC6979281 DOI: 10.1186/s40360-020-0385-8] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Accepted: 01/17/2020] [Indexed: 01/21/2023] Open
Abstract
Background Obesity is a multifactorial chronic disease that comprises several pathological events, such as adipose hypertrophy, fatty liver and insulin resistance. Inflammation is a key contributer to development of these events, and therefore, targeting inflammation is increasingly considered for management of obesity and its complications. The aim of the current study was to investigate therapeutic outcomes of anti-inflammatory activities of the natural compound Silibinin in reversing obesity and its complication in mice. Methods C57BL/6 male mice were fed high-fat diet for 8 weeks until development of obesity, and then injected with 50 mg/kg silibinin intraperitoneally twice per week, or vehicle for 8 weeks. Throughout the experiment, mice were continuously checked for body weight and food intake, and glucose tolerance test was performed toward the end of the experiment. Animals were sacrificed and serum and tissues were collected for biochemical, histological, and gene expression analysis to assess silibinin effects on adipose inflammation, fat accumulation, liver adipogenesis and glucose homeostasis. Results Silibinin treatment reversed adipose tissue inflammation and adipocyte hypertrophy, and blocked progression in weight gain and obesity development with no significant effects on rates of food intake. Silibinin also reversed fatty liver disease and restored glucose homeostasis in treated animals, and reversed hyperglycemia, hyperinsulinemia and hypertriglyceridemia. Conclusion In this study, we demonstrated that silibinin as an anti-inflammatory therapy is a potential alternative to manage obesity, as well as its related complications. Moreover, silibinin-based therapies could further evolve as a novel treatment to manage various inflammation-driven disorders.
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Affiliation(s)
- Mohammad Alsaggar
- Department of Pharmaceutical Technology, School of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid, 22110, Jordan.
| | - Shifa Bdour
- Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, Jordan
| | - Qutaibah Ababneh
- Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, Jordan
| | - Tamam El-Elimat
- Department of Medicinal Chemistry and Pharmacognosy, Jordan University of Science and Technology, Irbid, Jordan
| | - Nidal Qinna
- Department of Pharmacology and Biomedical Sciences, University of Petra, Amman, Jordan
| | - Karem H Alzoubi
- Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, Jordan
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Gong M, Wen S, Nguyen T, Wang C, Jin J, Zhou L. Converging Relationships of Obesity and Hyperuricemia with Special Reference to Metabolic Disorders and Plausible Therapeutic Implications. Diabetes Metab Syndr Obes 2020; 13:943-962. [PMID: 32280253 PMCID: PMC7125338 DOI: 10.2147/dmso.s232377] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 03/09/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Obesity and hyperuricemia mutually influence metabolic syndrome. This study discusses the metabolic relationships between obesity and hyperuricemia in terms of pathophysiology, complications, and treatments. METHODS We searched for preclinical or clinical studies on the pathophysiology, complications, and therapy of obesity and hyperuricemia on the PubMed database. RESULTS In this systemic review, we summarized our searching results on topics of pathophysiology, complications and therapeutic strategy. In pathophysiology, we firstly introduce genetic variations for obesity, hyperuricemia and their relationships by genetic studies. Secondly, we talk about the epigenetic influences on obesity and hyperuricemia. Thirdly, we describe the central metabolic regulation and the role of hyperuricemia. Then, we refer to the character of adipose tissue inflammation and oxidative stress in the obesity and hyperuricemia. In the last part of this topic, we reviewed the critical links of gut microbiota in the obesity and hyperuricemia. In the following part, we review the pathophysiology of major complications in obesity and hyperuricemia including insulin resistance and type 2 diabetes mellitus, chronic kidney disease, cardiovascular diseases, and cancers. Finally, we recapitulate the therapeutic strategies especially the novel pharmaceutic interventions for obesity and hyperuricemia, which concurrently show the mutual metabolic influences between two diseases. CONCLUSION The data reviewed here delineate the metabolic relationships between obesity and hyperuricemia, and provide a comprehensive overview of the therapeutic targets for the management of metabolic syndromes.
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Affiliation(s)
- Min Gong
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai201399, People’s Republic of China
| | - Song Wen
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai201399, People’s Republic of China
| | - Thiquynhnga Nguyen
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai201399, People’s Republic of China
| | - Chaoxun Wang
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai201399, People’s Republic of China
| | - Jianlan Jin
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai201399, People’s Republic of China
| | - Ligang Zhou
- Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai201399, People’s Republic of China
- Correspondence: Ligang Zhou Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai201399, ChinaTel +8613611927616 Email
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Oxidative/Antioxidative Status in Patients after Myocardial Infarction and in Those without Cardiovascular Event Depending on Anthropometric Factors Defining Body Weight. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16214077. [PMID: 31652762 PMCID: PMC6862597 DOI: 10.3390/ijerph16214077] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 10/14/2019] [Accepted: 10/19/2019] [Indexed: 01/04/2023]
Abstract
Obesity is one of the factors leading to the development of atherosclerosis. This metabolic disorder is associated with an increased production of reactive oxygen species, which affect the oxidative stress levels. The aim of this study was to evaluate oxidative/antioxidative status and to investigate the correlation between redox markers and anthropometric parameters and body composition in adult patients after myocardial infarction and in individuals without a cardiovascular event in the past. Descriptive data on socio-demographic, clinical, and anthropometric features and blood samples were collected and categorized into two equal groups: after myocardial infarction (study group (SG), n = 80) and without a cardiovascular event (control group (CG), n = 80). The oxidative/antioxidative status was assessed in plasma on the basis of total oxidative/capacitive status (PerOx), total antioxidative status/capacity (ImAnOx), and oxidized low-density lipoprotein (oxLDL). The oxLDL was significantly higher in the CG group compared to the SG group (p = 0.02). No significant differences were found with regard to PerOx and ImAnOx values between the groups studied. A significant positive correlation between PerOx and percentage of adipose tissue (FM%) and body adiposity index (BAI) was found in the two studied groups. ImAnOx significantly positively correlated with visceral adiposity indexes(VAIs) in SG and FM% in CG. OxLDL negatively correlated with body mass index and waist to hip circumference ratio in CG. The total oxidative/antioxidative status is related to the amount of adipose tissue and the BAIs of the subjects. It was observed that it correlates more frequently with the visceral distribution of body fat.
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Squillacioti G, Bellisario V, Grignani E, Mengozzi G, Bardaglio G, Dalmasso P, Bono R. The Asti Study: The Induction of Oxidative Stress in A Population of Children According to Their Body Composition and Passive Tobacco Smoking Exposure. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16030490. [PMID: 30744094 PMCID: PMC6388278 DOI: 10.3390/ijerph16030490] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Revised: 02/01/2019] [Accepted: 02/07/2019] [Indexed: 02/06/2023]
Abstract
Obesity and exposure to second-hand tobacco smoking (SHS) may influence oxidative stress (OS) levels, especially in children. This study investigated body composition and SHS influence on OS induction in the paediatric population. The first purpose was identifying an appropriate BMI standard for adiposity assessment in OS investigations. Secondly, SHS and obesity were analysed as inductors of OS. The epidemiologic sample involved 330 children. Three BMI (body mass index) references (IOTF, CDC, and WHO) and an impedentiometric scale supplied body-composition measurements. Partecipants filled out a questionnaire and provided urinary samples for biomarker quantifications: isoprostane (15-F2t IsoP) and cotinine as OS and SHS biomarker, respectively. Obesity prevalence changed over different BMI references (14%, 21%, and 34% for IOTF, CDC, and WHO, respectively). Obese children, by IOTF, showed an increase of 56% in 15-F2t IsoP compared to those normal weight (p = 0.020). Children belonging to the third and the fourth cotinine quartile compared to those of the first quartile had higher 15-F2t IsoP (1.45 ng/mg, 95% CI: 1.06⁻1.97, p = 0.020 and 2.04 ng/mg, 95% CI: 1.55⁻2.69, p < 0.0001, respectively). Obesity assessment in children requires appropriate BMI reference depending on research field. Both SHS exposure and obesity may increase OS in children.
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Affiliation(s)
- Giulia Squillacioti
- Department of Public Health and Pediatrics, University of Turin, 10126 Turin, Italy.
| | - Valeria Bellisario
- Department of Public Health and Pediatrics, University of Turin, 10126 Turin, Italy.
| | - Elena Grignani
- Maugeri Scientific Clinical Institutes, 27100 Pavia, Italy.
| | - Giulio Mengozzi
- City of Health and Science of Turin, Molinette Hospital, 10145 Turin, Italy.
| | - Giulia Bardaglio
- SUISM, Structure of Hygiene, Sport Sciences and Physical Activities, headquarters of Asti, University of Turin, 10126 Turin, Italy.
| | - Paola Dalmasso
- Department of Public Health and Pediatrics, University of Turin, 10126 Turin, Italy.
| | - Roberto Bono
- Department of Public Health and Pediatrics, University of Turin, 10126 Turin, Italy.
- SUISM, Structure of Hygiene, Sport Sciences and Physical Activities, headquarters of Asti, University of Turin, 10126 Turin, Italy.
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Cheng N, Chen S, Liu X, Zhao H, Cao W. Impact of SchisandraChinensis Bee Pollen on Nonalcoholic Fatty Liver Disease and Gut Microbiota in HighFat Diet Induced Obese Mice. Nutrients 2019; 11:E346. [PMID: 30736329 PMCID: PMC6412546 DOI: 10.3390/nu11020346] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 01/25/2019] [Accepted: 01/31/2019] [Indexed: 01/22/2023] Open
Abstract
Schisandrachinensisbee pollen has been used as a health food in China for centuries; however, its bioactive constituents and functions are not very clear. In this study, we investigated the phenolic compounds of Schisandrachinensisbee pollen extract (SCPE) by UHPLC-Q-Orbitrap-HRMS/HPLC-DAD-ECD and its prevention from nonalcoholic fatty liver disease (NAFLD) and modulation of gut microbiota in high fat diet induced obese C57BL/6 mice. The results showed that 12 phenolic compounds were identified in SCPE, and naringenin, rutin and chrysin were the main constituents. The content of naringenin reached 1.89 mg/g, and total phenolic content (TPC) of SCPE were 101.83 mg GA/g. After obese mice were administrated with SCPE at 7.86 and 15.72 g/kg BW for 8 weeks, body weight gains were reduced by 18.23% and 19.37%. SCPE could decrease fasting blood glucose, cut down the lipid accumulation in serum and liver, lessen oxidative injury and inflammation in obesity mice. Moreover, SCPE could effectively inhibit the formation of NAFLD by inhibition of LXR-α, SREBP-1c and FAS genes expression, and modulate the structural alteration of gut microbiota in obesity mice. These findings suggested that SCPE could attenuate the features of the metabolism syndrome in obesity mice, which can be used to prevent obesity and NAFLD of human beings.
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Affiliation(s)
- Ni Cheng
- College of Food Science and Technology, Northwest University, 229 North TaiBai Road, Xi'an 710069, China.
- Bee Product Research Center of Shaanxi Province, Xi'an 710065, China.
| | - Sinan Chen
- College of Food Science and Technology, Northwest University, 229 North TaiBai Road, Xi'an 710069, China.
| | - Xinyan Liu
- College of Food Science and Technology, Northwest University, 229 North TaiBai Road, Xi'an 710069, China.
| | - Haoan Zhao
- School of Chemical Engineering, Northwest University, 229 North TaiBai Road, Xi'an 710069, China.
| | - Wei Cao
- College of Food Science and Technology, Northwest University, 229 North TaiBai Road, Xi'an 710069, China.
- Bee Product Research Center of Shaanxi Province, Xi'an 710065, China.
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Oxidative Stress and Nutraceuticals in the Modulation of the Immune Function: Current Knowledge in Animals of Veterinary Interest. Antioxidants (Basel) 2019; 8:antiox8010028. [PMID: 30669304 PMCID: PMC6356544 DOI: 10.3390/antiox8010028] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Revised: 01/11/2019] [Accepted: 01/15/2019] [Indexed: 12/20/2022] Open
Abstract
In the veterinary sector, many papers deal with the relationships between inflammation and oxidative stress. However, few studies investigate the mechanisms of action of oxidised molecules in the regulation of immune cells. Thus, authors often assume that these events, sometime leading to oxidative stress, are conserved among species. The aim of this review is to draw the state-of-the-art of the current knowledge about the role of oxidised molecules and dietary antioxidant compounds in the regulation of the immune cell functions and suggest some perspectives for future investigations in animals of veterinary interest.
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Li J, Shen X. Oxidative stress and adipokine levels were significantly correlated in diabetic patients with hyperglycemic crises. Diabetol Metab Syndr 2019; 11:13. [PMID: 30774721 PMCID: PMC6364461 DOI: 10.1186/s13098-019-0410-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 01/31/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND To investigate the relationship between blood adipokine level and oxidative stress in diabetic patients with hyperglycemic crises before and after treatment. METHODS We measured superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, total antioxidant capacity (TAC), and levels of 8-iso-prostaglandin F2α (8-iso-PGF2α), adiponectin, leptin, and resistin in 63 diabetic patients with hyperglycemic crises. RESULTS Prior to treatment, patients with hyperglycemic crises had significantly lower serum SOD activity, TAC, and adiponectin and leptin levels, and higher serum levels of MDA, 8-iso-PGF2α, and resistin compared with the healthy control individuals (all at P < 0.05). After treatment, SOD, TAC, adiponectin, and leptin levels increased significantly, while MDA, 8-iso-PGF2α, and resistin levels decreased significantly (all at P < 0.05) in the patients. CONCLUSIONS Diabetic patients with hyperglycemic crises have increased oxidative stress, which is associated with serum adipokine abnormalities; improved oxidative stress after treatment suggests that oxidative stress may serve as target and/or indicator for the treatment of hyperglycemic crises.
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Affiliation(s)
- Juan Li
- Department of Emergency, Zhongshan Hospital Xiamen University, Xiamen, 361004 Fujian China
| | - Xingping Shen
- Department of Endocrinology, Zhongshan Hospital Xiamen University, Xiamen, 361004 Fujian China
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Polycystic Ovary Syndrome as a systemic disease with multiple molecular pathways: a narrative review. Endocr Regul 2018; 52:208-221. [DOI: 10.2478/enr-2018-0026] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Abstract
Polycystic Ovary Syndrome (PCOS) is characterized by hyperandrogenism, amenorrhea, and polycystic ovaries. This endocrinopathy is associated with many metabolic disorders such as dyslipidemia and insulin resistance, with increased risk of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular complications. Inflammation is likely to play an important role in the promoting these metabolic imbalances, while prothrombotic and pro-oxidative mechanisms further contribute to the cardiovascular risk of these patients. The etiology of PCOS is still not fully understood, but there is evidence of genetic and environmental components. This review aims to discuss some molecular pathways associated with PCOS that could contribute to the better understanding about this syndrome. Recent evidence suggests that intrauterine exposure of female mice to an excess of anti-Müllerian hormone may induce PCOS features in their post-natal life. High cytokine levels and cytokine gene polymorphisms also appear to be associated with the pathophysiology of PCOS. Furthermore, high levels of microparticles may contribute to the altered hemostasis and enhanced inflammation in PCOS. All these mechanisms may be relevant to clarify some aspects of PCOS pathogenesis and inspire new strategies to prevent the syndrome as well as treat its symptoms and mitigate the risk of long-term complications.
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Association of serum markers of oxidative stress with myocardial infarction and stroke: pooled results from four large European cohort studies. Eur J Epidemiol 2018; 34:471-481. [PMID: 30406496 DOI: 10.1007/s10654-018-0457-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2018] [Accepted: 10/23/2018] [Indexed: 12/13/2022]
Abstract
Oxidative stress contributes to endothelial dysfunction and is involved in the pathogenesis of myocardial infarction (MI) and stroke. However, associations of biomarkers of oxidative stress with MI and stroke have not yet been addressed in large cohort studies. A nested case-control design was applied in four population-based cohort studies from Germany, Czech Republic, Poland and Lithuania. Derivatives of reactive oxygen metabolites (d-ROMs) levels, as a proxy for the reactive oxygen species burden, and total thiol levels (TTL), as a proxy for the reductive capacity, were measured in baseline serum samples of 476 incident MI cases and 454 incident stroke cases as well as five controls per case individually matched by study center, age and sex. Statistical analyses were conducted with multi-variable adjusted conditional logistic regression models. d-ROMs levels were associated with both MI (odds ratio (OR), 1.21 [95% confidence interval (CI) 1.05-1.40] for 100 Carr units increase) and stroke (OR, 1.17 [95% CI 1.01-1.35] for 100 Carr units increase). TTL were only associated with stroke incidence (OR, 0.79 [95% CI 0.63-0.99] for quartiles 2-4 vs. quartile 1). The observed relationships were stronger with fatal than with non-fatal endpoints; association of TTL with fatal MI was statistically significant (OR, 0.69 [95% CI 0.51-0.93] for 100 μmol/L-increase). This pooled analysis of four large population-based cohorts suggests an important contribution of an imbalanced redox system to the etiology of mainly fatal MI and stroke events.
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Visceral fat and insulin resistance - what we know? Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2018; 163:19-27. [PMID: 30398218 DOI: 10.5507/bp.2018.062] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Accepted: 10/02/2018] [Indexed: 02/08/2023] Open
Abstract
One of the most significant challenges of current medicine is the increasing prevalence of obesity worldwide that is accompanied by a wide range of chronic health complications and increased mortality. White adipose tissue actively contributes to metabolic regulation by production of a variety of hormones and cytokines, commonly referred to as adipokines. The spectrum and quantity of adipokines produced by the adipose tissue of obese patients is directly or indirectly involved in much obesity-related pathology (type 2 diabetes mellitus, cardiovascular disease, inflammatory response). One of the underlying mechanisms linking obesity, diabetes, and cardiovascular complications is subclinical inflammation, primarily arising in visceral adipose tissue. Adipocyte size, number and polarization of lymphocytes and infiltrated macrophages are closely related to metabolic and obesity-related diseases. The storage capacity of hypertrophic adipocytes in obese patients is limited. This results in chronic energy overload and leads to increased apoptosis of adipocytes that in turn stimulates the infiltration of visceral adipose tissue by immune cells, in particular macrophages. These cells produce many proinflammatory factors; while the overall production of anti-inflammatory cytokines and adipokines is decreased. The constant release of proinflammatory factors into the circulation then contributes to a subclinical systemic inflammation, which is directly linked to the metabolic and cardiovascular complications of obesity.
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Inhibitory Effects of Cichorium Intybus Root Extract on the Proliferation and Lipogenesis of the SKBR3 Cells. INTERNATIONAL JOURNAL OF CANCER MANAGEMENT 2018. [DOI: 10.5812/ijcm.9436] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Differential actions of PPAR-α and PPAR-β/δ on beige adipocyte formation: A study in the subcutaneous white adipose tissue of obese male mice. PLoS One 2018; 13:e0191365. [PMID: 29351550 PMCID: PMC5774787 DOI: 10.1371/journal.pone.0191365] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Accepted: 01/03/2018] [Indexed: 12/18/2022] Open
Abstract
Background and aims Obesity compromises adipocyte physiology. PPARs are essential to adipocyte plasticity, but its isolated role in the browning phenomenon is not clear. This study aimed to examine whether activation of PPAR-α or PPAR-β/δ could induce beige cell depots in the subcutaneous white adipose tissue of diet-induced obese mice. Material and methods Sixty animals were randomly assigned to receive a control diet (C, 10% lipids) or a high-fat diet (HF, 50% lipids) for ten weeks. Then each group was re-divided to begin the treatments that lasted 4 weeks, totalizing six groups: C, C-α (C plus PPAR-α agonist, 2.5 mg/kg BM), C-β (C plus PPAR-β/δ agonist, 1 mg/kg BM), HF, HF-α (HF plus PPAR-α agonist), HF-β (HF plus PPAR-β/δ agonist). Results HF animals presented with overweight, glucose intolerance and subcutaneous white adipocyte hypertrophy. Both treatments significantly attenuated these parameters. Browning, verified by UCP1 positive beige cells and enhanced body temperature, was just observed in PPAR-α treated groups. PPAR-α agonism also elicited an enhanced gene expression of the thermogenesis effector UCP1, the beige-selective gene TMEM26 and the PRDM16, an essential gene for brown-like phenotype maintenance in the beige adipocytes when compared to their counterparts. The enhanced CIDEA and the reduced UCP1 gene levels might justify the white phenotype predominance after the treatment with the PPAR-β/δ agonist. Conclusions This work provides evidence that the PPAR-β/δ agonist ameliorated metabolic disorders through enhanced beta-oxidation and better tolerance to glucose, whereas the PPAR-α agonism was confirmed as a promising therapeutic target for treating metabolic diseases via beige cell induction and enhanced thermogenesis.
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Song M, Liu Y, Hui L. Preparation and characterization of acellular adipose tissue matrix using a combination of physical and chemical treatments. Mol Med Rep 2017; 17:138-146. [PMID: 29115567 PMCID: PMC5780077 DOI: 10.3892/mmr.2017.7857] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Accepted: 05/04/2017] [Indexed: 12/16/2022] Open
Abstract
Decellularized adipose extracellular matrix (ECM) has been used in the clinic to support the regeneration of adipose tissues. The methods used to produce adipose tissue ECM scaffolds exhibit distinct effects upon the structural and functional components of the resultant scaffold material. The current study presents an acellular ECM scaffold from human adipose tissues derived using successive physical and chemical treatments, including repeated freeze-thaw cycles followed by centrifugation, polar solvent extraction and enzymatic digestion. Cellular components, including nucleic acids were effectively removed without significant disruption of the morphology or structure of the ECM. The compositions of major ECM components were evaluated, including acid/pepsin soluble collagen, sulfated glycosaminoglycan and laminin. The decellularized ECM exhibited satisfactory mechanical properties. Cell seeding experiments involving human adipose-derived stem cells indicated that the decellularized ECM provided an inductive microenvironment for adipogenesis without the need for exogenous differentiation factors. Higher levels of glycerol-3-phosphate dehydrogenase activity were observed among induced cells in the ECM scaffolds when compared with induced cells in collagen type I scaffolds. In conclusion, the results suggested that the decellularized ECM, containing biological and chemical cues of native human ECM, may be an ideal scaffold material for autologous and allograft tissue engineering.
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Affiliation(s)
- Mei Song
- Burns and Plastic Surgery Center, General Hospital of Lanzhou Military Command of The People's Liberation Army, Institute of Orthopedics of Gansu Province, Lanzhou, Gansu 730050, P.R. China
| | - Yi Liu
- Burns and Plastic Surgery Center, General Hospital of Lanzhou Military Command of The People's Liberation Army, Institute of Orthopedics of Gansu Province, Lanzhou, Gansu 730050, P.R. China
| | - Ling Hui
- Department of Clinical Laboratories, General Hospital of Lanzhou Military Command of The People's Liberation Army, Key Laboratory of Stem Cells and Gene Medicine of Gansu Province, Lanzhou, Gansu 730050, P.R. China
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Waniek S, di Giuseppe R, Plachta-Danielzik S, Ratjen I, Jacobs G, Koch M, Borggrefe J, Both M, Müller HP, Kassubek J, Nöthlings U, Esatbeyoglu T, Schlesinger S, Rimbach G, Lieb W. Association of Vitamin E Levels with Metabolic Syndrome, and MRI-Derived Body Fat Volumes and Liver Fat Content. Nutrients 2017; 9:nu9101143. [PMID: 29057829 PMCID: PMC5691759 DOI: 10.3390/nu9101143] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Revised: 10/02/2017] [Accepted: 10/11/2017] [Indexed: 12/26/2022] Open
Abstract
We aimed to relate circulating α- and γ-tocopherol levels to a broad spectrum of adiposity-related traits in a cross-sectional Northern German study. Anthropometric measures were obtained, and adipose tissue volumes and liver fat were quantified by magnetic resonance imaging in 641 individuals (mean age 61 years; 40.6% women). Concentrations of α- and γ-tocopherol were measured using high performance liquid chromatography. Multivariable-adjusted linear and logistic regression were used to assess associations of circulating α- and γ-tocopherol/cholesterol ratio levels with visceral (VAT) and subcutaneous adipose tissue (SAT), liver signal intensity (LSI), fatty liver disease (FLD), metabolic syndrome (MetS), and its individual components. The α-tocopherol/cholesterol ratio was positively associated with VAT (β scaled by interquartile range (IQR): 0.036; 95%Confidence Interval (CI): 0.0003; 0.071) and MetS (Odds Ratio (OR): 1.83; 95% CI: 1.21–2.76 for 3rd vs. 1st tertile), and the γ-tocopherol/cholesterol ratio was positively associated with VAT (β scaled by IQR: 0.066; 95% CI: 0.027; 0.104), SAT (β scaled by IQR: 0.048; 95% CI: 0.010; 0.087) and MetS (OR: 1.87; 95% CI: 1.23–2.84 for 3rd vs. 1st tertile). α- and γ-tocopherol levels were positively associated with high triglycerides and low high density lipoprotein cholesterol levels (all Ptrend < 0.05). No association of α- and γ-tocopherol/cholesterol ratio with LSI/FLD was observed. Circulating vitamin E levels displayed strong associations with VAT and MetS. These observations lay the ground for further investigation in longitudinal studies.
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Affiliation(s)
- Sabina Waniek
- Institute of Epidemiology, Christian-Albrechts University of Kiel, 24105 Kiel, Germany.
| | - Romina di Giuseppe
- Institute of Epidemiology, Christian-Albrechts University of Kiel, 24105 Kiel, Germany.
| | | | - Ilka Ratjen
- Institute of Epidemiology, Christian-Albrechts University of Kiel, 24105 Kiel, Germany.
| | - Gunnar Jacobs
- Institute of Epidemiology, Christian-Albrechts University of Kiel, 24105 Kiel, Germany.
- Biobank PopGen, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
| | - Manja Koch
- Institute of Epidemiology, Christian-Albrechts University of Kiel, 24105 Kiel, Germany.
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
| | - Jan Borggrefe
- Institute of Diagnostic and Interventional Radiology, University Hospital Cologne, 50937 Cologne, Germany.
| | - Marcus Both
- Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
| | | | - Jan Kassubek
- Department of Neurology, University of Ulm, 89081 Ulm, Germany.
| | - Ute Nöthlings
- Department of Nutrition and Food Science, University of Bonn, 53113 Bonn, Germany.
| | - Tuba Esatbeyoglu
- Institute of Human Nutrition and Food Science, Christian-Albrechts University of Kiel, 24118 Kiel, Germany.
| | - Sabrina Schlesinger
- Institute for Biometrics and Epidemiology, German Diabetes Center (DDZ) at Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
| | - Gerald Rimbach
- Institute of Human Nutrition and Food Science, Christian-Albrechts University of Kiel, 24118 Kiel, Germany.
| | - Wolfgang Lieb
- Institute of Epidemiology, Christian-Albrechts University of Kiel, 24105 Kiel, Germany.
- Biobank PopGen, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
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Torday JS, Nielsen HC. The Molecular Apgar Score: A Key to Unlocking Evolutionary Principles. Front Pediatr 2017; 5:45. [PMID: 28373969 PMCID: PMC5357830 DOI: 10.3389/fped.2017.00045] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2016] [Accepted: 02/17/2017] [Indexed: 01/06/2023] Open
Abstract
One of the first "tools" used for systematically evaluating successful newborn transitional physiology at birth was the Apgar Score, devised by Virginia Apgar in 1953. This objective assessment tool allowed clinicians to immediately gauge the relative success of a newborn infant making the transition from the in utero liquid immersive environment to the ex utero gas environment in the delivery room during the first minutes after birth. The scoring system, although eponymous, is generally summarized as an acronym based on Appearance, Pulse, Grimace, Activity, and Respiration, criteria evaluated and scored at 1 and 5 min after birth. This common clinical appraisal is a guide for determining the elements of integrated physiology involved as the infant makes the transition from a "sea water" environment of 3% oxygen to a "land" environment in 21% oxygen. Appearance determines the perfusion of the skin with oxygenated blood-turning it pink; Pulse is the rate of heart beat, reflecting successful oxygen delivery to organs; Grimace, or irritability, is a functional marker for nervous system integration; Activity represents locomotor capacity; and, of course, Respiration represents pulmonary function as well as the successful neuro-feedback-mediated drive to breathe, supplying oxygen by inspiring atmospheric gas. Respiration, locomotion, and metabolism are fundamental processes adapted for vertebrate evolution from a water-based to an atmosphere-based life and are reflected by the Apgar Score. These physiologic processes last underwent major phylogenetic changes during the water-land transition some 300-400 million years ago, during which specific gene duplications occurred that facilitated terrestrial adaptation, in particular the parathyroid hormone-related protein receptor, the β-adrenergic receptor, and the glucocorticoid receptor. All these genetic traits and the gene regulatory networks they comprise represent the foundational substructure of the Apgar Score. As such, these molecular elements can be examined using a Molecular Apgar evaluation of keystone evolutionary events that predict successful evolutionary adaptation of physiologic functions necessary for neonatal transition and survival.
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Affiliation(s)
- John S Torday
- Pediatrics, Harbor - UCLA Medical Center , Torrance, CA , USA
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Kim DW, Kim EJ, Kim EN, Sung MW, Kwon TK, Cho YW, Kwon SK. Human Adipose Tissue Derived Extracellular Matrix and Methylcellulose Hydrogels Augments and Regenerates the Paralyzed Vocal Fold. PLoS One 2016; 11:e0165265. [PMID: 27768757 PMCID: PMC5074505 DOI: 10.1371/journal.pone.0165265] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Accepted: 10/07/2016] [Indexed: 12/15/2022] Open
Abstract
Vocal fold paralysis results from various etiologies and can induce voice changes, swallowing complications, and issues with aspiration. Vocal fold paralysis is typically managed using injection laryngoplasty with fat or synthetic polymers. Injection with autologous fat has shown excellent biocompatibility. However, it has several disadvantages such as unpredictable resorption rate, morbidities associated with liposuction procedure which has to be done in operating room under general anesthesia. Human adipose-derived extracellular matrix (ECM) grafts have been reported to form new adipose tissue and have greater biostability than autologous fat graft. Here, we present an injectable hydrogel that is constructed from adipose tissue derived soluble extracellular matrix (sECM) and methylcellulose (MC) for use in vocal fold augmentation. Human sECM derived from adipose tissue was extracted using two major steps—ECM was isolated from human adipose tissue and was subsequently solubilized. Injectable sECM/MC hydrogels were prepared by blending of sECM and MC. Sustained vocal fold augmentation and symmetric vocal fold vibration were accomplished by the sECM/MC hydrogel in paralyzed vocal fold which were confirmed by laryngoscope, histology and a high-speed imaging system. There were increased number of collagen fibers and fatty granules at the injection site without significant inflammation or fibrosis. Overall, these results indicate that the sECM/MC hydrogel can enhance vocal function in paralyzed vocal folds without early resorption and has potential as a promising material for injection laryngoplasty for stable vocal fold augmentation which can overcome the shortcomings of autologous fat such as unpredictable duration and morbidity associated with the fat harvest.
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Affiliation(s)
- Dong Wook Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Eun Ji Kim
- Department of Chemical Engineering, Hanyang University, Ansan, Gyeonggi-do 426–791, Republic of Korea
| | - Eun Na Kim
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Myung Whun Sung
- Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Tack-Kyun Kwon
- Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yong Woo Cho
- Department of Chemical Engineering, Hanyang University, Ansan, Gyeonggi-do 426–791, Republic of Korea
- * E-mail: (SKK); (YWC)
| | - Seong Keun Kwon
- Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
- * E-mail: (SKK); (YWC)
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Kilic E, Özer ÖF, Erek Toprak A, Erman H, Torun E, Kesgin Ayhan S, Caglar HG, Selek S, Kocyigit A. Oxidative Stress Status in Childhood Obesity: A Potential Risk Predictor. Med Sci Monit 2016; 22:3673-3679. [PMID: 27733746 PMCID: PMC5066503 DOI: 10.12659/msm.897965] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Background Childhood obesity characterized by excessive fat in the body is one of the most serious health problems worldwide due to the social, medical, and physiological complications. Obesity and associated diseases are triggering factors for oxidative stress and inflammation. The aim of this study was to explore the possible association between childhood obesity and inflammatory and oxidative status. Material/Methods Thirty-seven obese children and 37 healthy controls selected from among children admitted to BLIND University Paediatrics Department were included in the study. Anthropometric measurements were performed using standard methods. Glucose, lipid parameters, CRP, insulin, total oxidant status (TOS), total anti-oxidant status (TAS) levels, and total thiol levels (TTL) were measured in serum. HOMA index (HOMA-IR) were calculated. The differences between the groups were evaluated statistically using the Mann-Whitney U test. Results Body mass index was significantly higher in the obese group (median: 28.31(p<0.001). Glucose metabolism, insulin, and HOMA-IR levels were significantly higher in the obese group (both p<0.001). Total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride levels were significantly higher in the obese group (p<0.001). TAS (med: 2.5 μmol Trolox eq/L (1.7–3.3)) and TOS (med: 49.1 μmol H2O2 eq/L (34.5–78.8)) levels and TTL (med: 0.22 mmol/L (0.16–0.26)) were significantly higher in the obese group (p=0.001). CRP levels showed positive correlation with TOS and negative correlation with TTL levels (p=0.005, r=0.473; p=0.01, r=−0.417; respectively). TTL levels exhibited negative correlation with TOS levels (p=0.03, r=−0.347). Conclusions In conclusion, obese children were exposed to more oxidative burden than children with normal weight. Increased systemic oxidative stress induced by childhood obesity can cause development of obesity-related complications and diseases. Widely focussed studies are required on the use of oxidative parameters as early prognostic parameters in detection of obesity-related complications.
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Affiliation(s)
- Elif Kilic
- Department of Biochemistry, Bezmialem Vakif University, Medical Faculty, Istanbul, Turkey
| | - Ömer Faruk Özer
- Department of Biochemistry, Bezmialem Vakif University, Medical Faculty, Istanbul, Turkey
| | - Aybala Erek Toprak
- Department of Biochemistry, Medeniyet University, Medical Faculty, Istanbul, Turkey
| | - Hayriye Erman
- Department of Biochemistry, Medeniyet University, Medical Faculty, Istanbul, Turkey
| | - Emel Torun
- Department of Paediatrics, Bezmialem Vakif University, Medical Faculty, Istanbul, Turkey
| | - Sıddıka Kesgin Ayhan
- Department of Biochemistry, Bezmialem Vakif University, Medical Faculty, Istanbul, Turkey
| | - Hifa Gülru Caglar
- Department of Biochemistry, Bezmialem Vakif University, Medical Faculty, Istanbul, Turkey
| | - Sahbettin Selek
- Department of Biochemistry, Bezmialem Vakif University, Medical Faculty, Istanbul, Turkey
| | - Abdurrahim Kocyigit
- Department of Biochemistry, Bezmialem Vakif University, Medical Faculty, Istanbul, Turkey
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Mafort TT, Rufino R, Costa CH, Lopes AJ. Obesity: systemic and pulmonary complications, biochemical abnormalities, and impairment of lung function. Multidiscip Respir Med 2016; 11:28. [PMID: 27408717 PMCID: PMC4940831 DOI: 10.1186/s40248-016-0066-z] [Citation(s) in RCA: 174] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Accepted: 05/10/2016] [Indexed: 12/11/2022] Open
Abstract
Obesity is currently one of the major epidemics of this millennium and affects individuals throughout the world. It causes multiple systemic complications, some of which result in severe impairment of organs and tissues. These complications involve mechanical changes caused by the accumulation of adipose tissue and the numerous cytokines produced by adipocytes. Obesity also significantly interferes with respiratory function by decreasing lung volume, particularly the expiratory reserve volume and functional residual capacity. Because of the ineffectiveness of the respiratory muscles, strength and resistance may be reduced. All these factors lead to inspiratory overload, which increases respiratory effort, oxygen consumption, and respiratory energy expenditure. It is noteworthy that patterns of body fat distribution significantly influence the function of the respiratory system, likely via the direct mechanical effect of fat accumulation in the chest and abdominal regions. Weight loss caused by various types of treatment, including low-calorie diet, intragastric balloon, and bariatric surgery, significantly improves lung function and metabolic syndrome and reduces body mass index. Despite advances in the knowledge of pulmonary and systemic complications associated with obesity, longitudinal randomized studies are needed to assess the impact of weight loss on metabolic syndrome and lung function.
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Affiliation(s)
- Thiago Thomaz Mafort
- Laboratory of Respiration Physiology, Pulmonary Medicine Department, Pedro Ernesto University Hospital, State University of Rio de Janeiro, Boulevard 28 de Setembro, 77, Vila Isabel, 20551-030 Rio de Janeiro Brazil
| | - Rogério Rufino
- Laboratory of Respiration Physiology, Pulmonary Medicine Department, Pedro Ernesto University Hospital, State University of Rio de Janeiro, Boulevard 28 de Setembro, 77, Vila Isabel, 20551-030 Rio de Janeiro Brazil ; Postgraduate Programme in Medical Sciences, State University of Rio de Janeiro, Av. Prof. Manoel de Abreu, 444, Vila Isabel, 20550-170 Rio de Janeiro Brazil
| | - Cláudia Henrique Costa
- Laboratory of Respiration Physiology, Pulmonary Medicine Department, Pedro Ernesto University Hospital, State University of Rio de Janeiro, Boulevard 28 de Setembro, 77, Vila Isabel, 20551-030 Rio de Janeiro Brazil ; Postgraduate Programme in Medical Sciences, State University of Rio de Janeiro, Av. Prof. Manoel de Abreu, 444, Vila Isabel, 20550-170 Rio de Janeiro Brazil
| | - Agnaldo José Lopes
- Laboratory of Respiration Physiology, Pulmonary Medicine Department, Pedro Ernesto University Hospital, State University of Rio de Janeiro, Boulevard 28 de Setembro, 77, Vila Isabel, 20551-030 Rio de Janeiro Brazil ; Postgraduate Programme in Medical Sciences, State University of Rio de Janeiro, Av. Prof. Manoel de Abreu, 444, Vila Isabel, 20550-170 Rio de Janeiro Brazil
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Increased Gustatory Response Score in Obesity and Association Levels with IL-6 and Leptin. J Nutr Metab 2016; 2016:7924052. [PMID: 27413547 PMCID: PMC4928000 DOI: 10.1155/2016/7924052] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Revised: 05/08/2016] [Accepted: 05/17/2016] [Indexed: 12/30/2022] Open
Abstract
Background. The aim of this study was to investigate the relationship between the circulating IL-6 and leptin levels with taste alteration in young obese patients. Methods. A retrospective case-control study was conducted in thirty obese patients and thirty age- and sex-matched healthy controls. Results. Circulating levels of IL-6 and leptin were significantly increased in obese patients than in controls. However, catalase and ORAC levels were significantly decreased in obese patients compared to controls. Additionally, obese participants had high scores for the detection of fats (gustatory response scores [GRS]; p < 0.001). Moreover, IL-6 and leptin were strongly associated with GRS alteration among patients with GRS 4 (resp., OR =17.5 [95% CI, 1.56–193.32; p = 0.007]; OR = 16 [95% CI, 1.69–151.11; p = 0.006]). For the Mantel-Haenszel common odds ratio estimate (MH OR), IL-6 and leptin were strongly associated with obesity, in patients with either GRS 4 or GRS > 4 (resp., MH OR = 8.77 [95% CI, 2.06–37.44; p = 0.003]; MH OR = 5.76 [95% CI, 1.64–20.24; p = 0.006]). Conclusions. In a low grade inflammation linked to obesity, taste alteration is associated with high levels of IL-6 and leptin.
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46
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Martin R, Shapiro JI. Role of adipocytes in hypertension. World J Hypertens 2016; 6:66-75. [DOI: 10.5494/wjh.v6.i2.66] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Accepted: 06/02/2016] [Indexed: 02/06/2023] Open
Abstract
Although it has known for some time that obesity is associated with salt sensitivity and hypertension, recent data suggests that the adipocyte may actually be the proximate cause of this physiological changes. In the following review, the data demonstrating this association as well as the potentially operative pathophysiological mechanisms are reviewed and discussed.
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Jumabay M, Boström KI. Dedifferentiated fat cells: A cell source for regenerative medicine. World J Stem Cells 2015; 7:1202-1214. [PMID: 26640620 PMCID: PMC4663373 DOI: 10.4252/wjsc.v7.i10.1202] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Revised: 04/02/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
The identification of an ideal cell source for tissue regeneration remains a challenge in the stem cell field. The ability of progeny cells to differentiate into other cell types is important for the processes of tissue reconstruction and tissue engineering and has clinical, biochemical or molecular implications. The adaptation of stem cells from adipose tissue for use in regenerative medicine has created a new role for adipocytes. Mature adipocytes can easily be isolated from adipose cell suspensions and allowed to dedifferentiate into lipid-free multipotent cells, referred to as dedifferentiated fat (DFAT) cells. Compared to other adult stem cells, the DFAT cells have unique advantages in their abundance, ease of isolation and homogeneity. Under proper condition in vitro and in vivo, the DFAT cells have exhibited adipogenic, osteogenic, chondrogenic, cardiomyogenc, angiogenic, myogenic, and neurogenic potentials. In this review, we first discuss the phenomena of dedifferentiation and transdifferentiation of cells, and then dedifferentiation of adipocytes in particular. Understanding the dedifferentiation process itself may contribute to our knowledge of normal growth processes, as well as mechanisms of disease. Second, we highlight new developments in DFAT cell culture and summarize the current understanding of DFAT cell properties. The unique features of DFAT cells are promising for clinical applications such as tissue regeneration.
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48
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Gamboa-Gómez CI, Rocha-Guzmán NE, Gallegos-Infante JA, Moreno-Jiménez MR, Vázquez-Cabral BD, González-Laredo RF. Plants with potential use on obesity and its complications. EXCLI JOURNAL 2015; 14:809-31. [PMID: 26869866 PMCID: PMC4746997 DOI: 10.17179/excli2015-186] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/11/2015] [Accepted: 06/16/2015] [Indexed: 01/07/2023]
Abstract
Obesity is the most prevalent nutritional disease and a growing public health problem worldwide. This disease is a causal component of the metabolic syndrome related with abnormalities, including hyperglycemia, dyslipidemia, hypertension, inflammation, among others. There are anti-obesity drugs, affecting the fundamental processes of the weight regulation; however they have shown serious side effects, which outweigh their beneficial effects. Most recent studies on the treatment of obesity and its complications have focused on the potential role of different plants preparation that can exert a positive effect on the mechanisms involved in this pathology. For instance, anti-obesity effects of green tea and its isolated active principles have been reported in both in vitro (cell cultures) and in vivo (animal models) that possess healthy effects, decreasing adipose tissue through reduction of adipocytes differentiation and proliferation. A positive effect in lipid profile, and lipid and carbohydrates metabolisms were demonstrated as well. In addition, anti-inflammatory and antioxidant activities were studied. However, the consumption of green tea and its products is not that common in Western countries, where other plants with similar bioactivity predominate; nevertheless, the effect extension has not been analyzed in depth, despite of their potential as alternative treatment for obesity. In this review the anti-obesity potential and reported mechanisms of action of diverse plants such as: Camellia sinensis, Hibiscus sabdariffa, Hypericum perforatum, Persea americana, Phaseolus vulgaris, Capsicum annuum, Rosmarinus officinalis, Ilex paraguariensis, Citrus paradisi, Citrus limon, Punica granatum, Aloe vera, Taraxacum officinale and Arachis hypogaea is summarized. We consider the potential of these plants as natural alternative treatments of some metabolic alterations associated with obesity.
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Affiliation(s)
| | - Nuria E. Rocha-Guzmán
- Instituto Tecnológico de Durango, Felipe Pescador 1830 Ote., 34080 Durango, Dgo., México
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Perry RJ, Camporez JPG, Kursawe R, Titchenell PM, Zhang D, Perry CJ, Jurczak MJ, Abudukadier A, Han MS, Zhang XM, Ruan HB, Yang X, Caprio S, Kaech SM, Sul HS, Birnbaum MJ, Davis RJ, Cline GW, Petersen KF, Shulman GI. Hepatic acetyl CoA links adipose tissue inflammation to hepatic insulin resistance and type 2 diabetes. Cell 2015; 160:745-758. [PMID: 25662011 DOI: 10.1016/j.cell.2015.01.012] [Citation(s) in RCA: 535] [Impact Index Per Article: 53.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2014] [Revised: 11/10/2014] [Accepted: 01/05/2015] [Indexed: 01/15/2023]
Abstract
Impaired insulin-mediated suppression of hepatic glucose production (HGP) plays a major role in the pathogenesis of type 2 diabetes (T2D), yet the molecular mechanism by which this occurs remains unknown. Using a novel in vivo metabolomics approach, we show that the major mechanism by which insulin suppresses HGP is through reductions in hepatic acetyl CoA by suppression of lipolysis in white adipose tissue (WAT) leading to reductions in pyruvate carboxylase flux. This mechanism was confirmed in mice and rats with genetic ablation of insulin signaling and mice lacking adipose triglyceride lipase. Insulin's ability to suppress hepatic acetyl CoA, PC activity, and lipolysis was lost in high-fat-fed rats, a phenomenon reversible by IL-6 neutralization and inducible by IL-6 infusion. Taken together, these data identify WAT-derived hepatic acetyl CoA as the main regulator of HGP by insulin and link it to inflammation-induced hepatic insulin resistance associated with obesity and T2D.
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Affiliation(s)
- Rachel J Perry
- Howard Hughes Medical Institute, Yale University, New Haven, CT 06519, USA; Department of Internal Medicine, Yale University, New Haven, CT 06520, USA; Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06520, USA
| | | | - Romy Kursawe
- Department of Internal Medicine, Yale University, New Haven, CT 06520, USA
| | - Paul M Titchenell
- The Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Dongyan Zhang
- Howard Hughes Medical Institute, Yale University, New Haven, CT 06519, USA
| | - Curtis J Perry
- Department of Immunobiology, Yale University, New Haven, CT 06520, USA
| | - Michael J Jurczak
- Department of Internal Medicine, Yale University, New Haven, CT 06520, USA
| | | | - Myoung Sook Han
- Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
| | - Xian-Man Zhang
- Howard Hughes Medical Institute, Yale University, New Haven, CT 06519, USA
| | - Hai-Bin Ruan
- Department of Comparative Medicine, Yale University, New Haven, CT 06520, USA
| | - Xiaoyong Yang
- Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06520, USA; Department of Comparative Medicine, Yale University, New Haven, CT 06520, USA
| | - Sonia Caprio
- Department of Pediatrics, Yale University, New Haven, CT 06520, USA
| | - Susan M Kaech
- Department of Immunobiology, Yale University, New Haven, CT 06520, USA
| | - Hei Sook Sul
- Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA
| | - Morris J Birnbaum
- The Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Roger J Davis
- Howard Hughes Medical Institute, Yale University, New Haven, CT 06519, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
| | - Gary W Cline
- Department of Internal Medicine, Yale University, New Haven, CT 06520, USA
| | - Kitt Falk Petersen
- Department of Internal Medicine, Yale University, New Haven, CT 06520, USA
| | - Gerald I Shulman
- Howard Hughes Medical Institute, Yale University, New Haven, CT 06519, USA; Department of Internal Medicine, Yale University, New Haven, CT 06520, USA; Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06520, USA.
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50
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Marseglia L, Manti S, D'Angelo G, Nicotera A, Parisi E, Di Rosa G, Gitto E, Arrigo T. Oxidative stress in obesity: a critical component in human diseases. Int J Mol Sci 2014; 16:378-400. [PMID: 25548896 PMCID: PMC4307252 DOI: 10.3390/ijms16010378] [Citation(s) in RCA: 615] [Impact Index Per Article: 55.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2014] [Accepted: 12/15/2014] [Indexed: 02/07/2023] Open
Abstract
Obesity, a social problem worldwide, is characterized by an increase in body weight that results in excessive fat accumulation. Obesity is a major cause of morbidity and mortality and leads to several diseases, including metabolic syndrome, diabetes mellitus, cardiovascular, fatty liver diseases, and cancer. Growing evidence allows us to understand the critical role of adipose tissue in controlling the physic-pathological mechanisms of obesity and related comorbidities. Recently, adipose tissue, especially in the visceral compartment, has been considered not only as a simple energy depository tissue, but also as an active endocrine organ releasing a variety of biologically active molecules known as adipocytokines or adipokines. Based on the complex interplay between adipokines, obesity is also characterized by chronic low grade inflammation with permanently increased oxidative stress (OS). Over-expression of oxidative stress damages cellular structures together with under-production of anti-oxidant mechanisms, leading to the development of obesity-related complications. The aim of this review is to summarize what is known in the relationship between OS in obesity and obesity-related diseases.
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Affiliation(s)
- Lucia Marseglia
- Neonatal and Pediatric Intensive Care Unit, Department of Pediatrics, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy.
| | - Sara Manti
- Unit of Paediatric Genetics and Immunology, Department of Paediatrics, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy.
| | - Gabriella D'Angelo
- Neonatal and Pediatric Intensive Care Unit, Department of Pediatrics, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy.
| | - Antonio Nicotera
- Unit of Child Neurology and Psychiatry, Department of Pediatrics, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy.
| | - Eleonora Parisi
- Unit of Child Neurology and Psychiatry, Department of Pediatrics, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy.
| | - Gabriella Di Rosa
- Unit of Child Neurology and Psychiatry, Department of Pediatrics, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy.
| | - Eloisa Gitto
- Neonatal and Pediatric Intensive Care Unit, Department of Pediatrics, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy.
| | - Teresa Arrigo
- Unit of Paediatric Genetics and Immunology, Department of Paediatrics, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy.
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