GPER Deficiency in Male Mice Results in Insulin Resistance, Dyslipidemia, and a Proinflammatory State

Estrogen is an important regulator of metabolic syndrome, a collection of abnormalities including obesity, insulin resistance/glucose intolerance, hypertension, dyslipidemia, and inflammation, which together lead to increased risk of cardiovascular disease and diabetes. The role of the G protein-coupled estrogen receptor (GPER/GPR30), particularly in males, in these pathologies remains unclear. We therefore sought to determine whether loss of GPER contributes to aspects of metabolic syndrome in male mice. Although 6-month-old male and female GPER knockout (KO) mice displayed increased body weight compared with wild-type littermates, only female GPER KO mice exhibited glucose intolerance at this age. Weight gain in male GPER KO mice was associated with increases in both visceral and sc fat. GPER KO mice, however, exhibited no differences in food intake or locomotor activity. One-year-old male GPER KO mice displayed an abnormal lipid profile with higher cholesterol and triglyceride levels. Fasting blood glucose levels remained normal, whereas insulin levels were elevated. Although insulin resistance was evident in GPER KO male mice from 6 months onward, glucose intolerance was pronounced only at 18 months of age. Furthermore, by 2 years of age, a proinflammatory phenotype was evident, with increases in the proinflammatory and immunomodulatory cytokines IL-1β, IL-6, IL-12, TNFα, monocyte chemotactic protein-1, interferon γ-induced protein 10, and monokine induced by interferon gamma and a concomitant decrease in the adipose-specific cytokine adiponectin. In conclusion, our study demonstrates for the first time that in male mice, GPER regulates metabolic parameters associated with obesity and diabetes.

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Clinical and genetic risk factors for new-onset diabetes mellitus after transplantation (NODAT) in major transplant centres in Malaysia

BMC Nephrology ◽

10.1186/s12882-020-02052-9 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Rhanye Mac Guad ◽

Andrew W. Taylor-Robinson ◽

Yuan Seng Wu ◽

Siew Hua Gan ◽

Nur Lisa Zaharan ◽

...

Keyword(s):

Renal Transplantation ◽

Blood Glucose ◽

Renal Transplant ◽

Fasting Blood Glucose ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Increased Risk ◽

Daily Dose ◽

One Year ◽

New Onset

Abstract Background New-onset diabetes after transplantation (NODAT) is associated with reduced patient and graft survival. This study examined the clinical and selected genetic factors associated with NODAT among renal-transplanted Malaysian patients. Methods This study included 168 non-diabetic patients (58% males, 69% of Chinese ethnicity) who received renal transplantation between 1st January 1994 to 31st December 2014, and were followed up in two major renal transplant centres in Malaysia. Fasting blood glucose levels were used to diagnose NODAT in patients who received renal transplantation within 1 year. Two single nucleotide polymorphisms (SNPs), namely; rs1494558 (interleukin-7 receptor, IL-7R) and rs2232365 (mannose-binding leptin-2, MBL2) were selected and genotyped using Sequenom MassArray platform. Cox proportional hazard regression analyses were used to examine the risk of developing NODAT according to the different demographics and clinical covariates, utilizing four time-points (one-month, three-months, six-months, one-year) post-transplant. Results Seventeen per cent of patients (n = 29, 55% males, 69% Chinese) were found to have developed NODAT within one-year of renal transplantation based on their fasting blood glucose levels. NODAT patients had renal transplantation at an older age compared to non-NODAT (39.3 ± 13.4 vs 33.9 ± 11.8 years, p = 0.03). In multivariate analysis, renal-transplanted patients who received a higher daily dose of cyclosporine (mg) were associated with increased risk of NODAT (Hazard ratio (HR) =1.01 per mg increase in dose, 95% confidence interval (CI) 1.00–1.01, p = 0.002). Other demographic (gender, ethnicities, age at transplant) and clinical factors (primary kidney disease, type of donor, place of transplant, type of calcineurin inhibitors, duration of dialysis pre-transplant, BMI, creatinine levels, and daily doses of tacrolimus and prednisolone) were not found to be significantly associated with risk of NODAT. GA genotype of rs1494558 (HR = 3.15 95% CI 1.26, 7.86) and AG genotype of rs2232365 (HR = 2.57 95% CI 1.07, 6.18) were associated with increased risk of NODAT as compared to AA genotypes. Conclusion The daily dose of cyclosporine and SNPs of IL-7R (rs1494558) and MBL2 (rs2232365) genes are significantly associated with the development of NODAT in the Malaysian renal transplant population.

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Exposure to Common Food Additive Carrageenan Alone Leads to Fasting Hyperglycemia and in Combination with High Fat Diet Exacerbates Glucose Intolerance and Hyperlipidemia without Effect on Weight

Journal of Diabetes Research ◽

10.1155/2015/513429 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13 ◽

Cited By ~ 17

Author(s):

Sumit Bhattacharyya ◽

Leo Feferman ◽

Terry Unterman ◽

Joanne K. Tobacman

Keyword(s):

Blood Glucose ◽

Glucose Tolerance ◽

Glucose Intolerance ◽

High Fat Diet ◽

Fasting Blood Glucose ◽

Food Additive ◽

High Fat ◽

Glucose Levels ◽

Fat Consumption ◽

One Year

Aims. Major aims were to determine whether exposure to the commonly used food additive carrageenan could induce fasting hyperglycemia and could increase the effects of a high fat diet on glucose intolerance and dyslipidemia.Methods. C57BL/6J mice were exposed to either carrageenan, high fat diet, or the combination of high fat diet and carrageenan, or untreated, for one year. Effects on fasting blood glucose, glucose tolerance, lipid parameters, weight, glycogen stores, and inflammation were compared.Results. Exposure to carrageenan led to glucose intolerance by six days and produced elevated fasting blood glucose by 23 weeks. Effects of carrageenan on glucose tolerance were more severe than from high fat alone. Carrageenan in combination with high fat produced earlier onset of fasting hyperglycemia and higher glucose levels in glucose tolerance tests and exacerbated dyslipidemia. In contrast to high fat, carrageenan did not lead to weight gain. In hyperinsulinemic, euglycemic clamp studies, the carrageenan-exposed mice had higher early glucose levels and lower glucose infusion rate and longer interval to achieve the steady-state.Conclusions. Carrageenan in the Western diet may contribute to the development of diabetes and the effects of high fat consumption. Carrageenan may be useful as a nonobese model of diabetes in the mouse.

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rs1501299 Polymorphism in the Adiponectin Gene and Their Association with Total Adiponectin Levels, Insulin Resistance and Metabolic Syndrome in Obese Subjects

Annals of Nutrition and Metabolism ◽

10.1159/000453401 ◽

2016 ◽

Vol 69 (3-4) ◽

pp. 226-231 ◽

Cited By ~ 8

Author(s):

Daniel Antonio de Luis ◽

Olatz Izaola ◽

Beatriz de la Fuente ◽

David Primo ◽

Hilda Fernandez Ovalle ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Body Weight ◽

Fasting Blood Glucose ◽

Model Assessment ◽

Adipoq Gene ◽

Total Adiponectin ◽

Increased Risk ◽

Obese Subjects ◽

And Gender

Background and Aims: The aim of this study was to determine the association of single nucleotide polymorphism rs1501299 in the ADIPOQ gene with body weight, insulin resistance, serum adipokine levels and metabolic syndrome (MetS). Methods: The study involved a population of 1,007 adult obese subjects. Parameters like body weight, fat mass, waist circumferences, blood pressure, fasting blood glucose, C-reactive protein, insulin concentration, homeostasis model assessment for insulin resistance (HOMA-IR), lipid profile and adipocytokines levels (leptin, adiponectin and resistin) were all measured. The genotype of ADIPOQ gene polymorphism (rs1501299) was evaluated. Results: Insulin levels (GG: 13.6 ± 5.1 mUI/l vs. GT: 14.1 ± 5.2 mUI/l vs. TT: 16.6 ± 5.2 mUI/l; p < 0.05) and HOMA-IR (GG: 3.3 ± 1.5 units vs. GT: 4.1 ± 1.1 units vs. TT: 4.5 ± 1.3 units; p < 0.05) were higher in T-allele carriers than they were in non-T-allele carriers. Total adiponectin levels (GG: 20.2 ± 2.4 ng/dl vs. GT: 15.8 ± 3.4 ng/dl vs. TT: 13.7 ± 1.4 ng/dl; p < 0.05) were lower in T-allele carriers than they were in non-T-allele carriers. Logistic regression analysis indicated that subjects with T allele were associated with an increased risk of MetS (OR 1.15, 95% CI 1.08-1.25, p = 0.033) and an increased risk of hyperglycemia (OR 1.99, 95% CI 1.37-2.55, p = 0.028) after adjusting by age and gender. Conclusions: These data suggest an important role of this ADIPOQ variant at position +276 on insulin resistance, total adiponectin levels and MetS.

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Transgenerational Inheritance of Glucose Intolerance in a Mouse Model of Neonatal Overnutrition

Endocrinology ◽

10.1210/en.2010-0684 ◽

2010 ◽

Vol 151 (12) ◽

pp. 5617-5623 ◽

Cited By ~ 87

Author(s):

Thais Pentinat ◽

Marta Ramon-Krauel ◽

Judith Cebria ◽

Ruben Diaz ◽

Josep C. Jimenez-Chillaron

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Mouse Model ◽

Glucose Intolerance ◽

Cell Function ◽

Male Mice ◽

Rapid Weight Gain ◽

Abnormal Growth ◽

Peripheral Insulin Resistance ◽

The Metabolic Syndrome

Epidemiological and clinical data show that rapid weight gain early in life is strongly associated with several components of the metabolic syndrome. Strikingly, abnormal growth rates in early life can additionally influence diabetes risk in subsequent generations. Here we aim to study whether neonatal overgrowth induces diabetes in offspring and grand-offspring of affected individuals using a mouse model of neonatal overfeeding. We induced neonatal overgrowth (ON-F0) by culling offspring to four pups per dam during lactation. By age 4 months, ON-F0 mice developed many features of the metabolic syndrome, including obesity, insulin resistance, and glucose intolerance. We then studied whether male offspring (ON-F1) and grand-offspring (ON-F2) of ON-F0 male mice, which were not overfed during lactation, developed features of the metabolic syndrome with aging. ON-F1 mice developed fed and fasting hyperinsulimemia, hypertryglyceridemia, insulin resistance, and glucose intolerance, but not obesity, by age 4 months. In contrast, ON-F2 male mice showed a more moderate phenotype and only developed fasting hyperglycemia and glucose intolerance by age 4 months. Impaired glucose tolerance in ON-F1 and ON-F2 mice appeared to be accounted for primarily by peripheral insulin resistance, because beta-cell function remained normal or even increased in these cohorts. Nutritional challenges occurring during sensitive periods of development may have adverse metabolic consequences well beyond the lifespan of affected individuals and manifest in subsequent generations. Transgenerational progression of metabolic phenotypes through the male lineage supports a potential role for epigenetic mechanisms in mediating these effects.

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Association of Candidate Gene Polymorphism with Metabolic Syndrome among Mongolian Subjects: A Case-Control Study

Medical Sciences ◽

10.3390/medsci8030038 ◽

2020 ◽

Vol 8 (3) ◽

pp. 38

Author(s):

Ariunbold Chuluun-Erdene ◽

Orgil Sengeragchaa ◽

Tsend-Ayush Altangerel ◽

Purevjal Sanjmyatav ◽

Batnaran Dagdan ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Fasting Blood Glucose ◽

Density Lipoprotein ◽

Control Group ◽

Case Group ◽

Individual Snps ◽

Increased Risk

Metabolic syndrome (MetS) is complex and determined by the interaction between genetic and environmental factors and their influence on obesity, insulin resistance, and related traits associated with diabetes and cardiovascular disease risk. Some dynamic markers, including adiponectin (ADIPOQ), brain-derived neurotrophic factor (BDNF), and lipoprotein lipase (LPL), are implicated in MetS; however, the influence of their genetic variants on MetS susceptibility varies in racial and ethnic groups. We investigated the association of single nucleotide polymorphism (SNP)-SNP interactions among nine SNPs in six genes with MetS’s genetic predisposition in Mongolian subjects. A total of 160 patients with MetS for the case group and 144 healthy individuals for the control group were selected to participate in this study. Regression analysis of individual SNPs showed that the ADIPOQ + 45GG (odds ratio (OR) = 2.09, p = 0.011) and P+P+ of LPL PvuII (OR = 2.10, p = 0.038) carriers had an increased risk of MetS. Conversely, G allele of LPL S447X (OR = 0.45, p = 0.036) and PGC-1α 482Ser (OR = 0.26, p = 0.001) allele were estimated as protective factors, respectively. Moreover, a haplotype containing the G-P+-G combination was related to MetS. Significant loci were also related to body mass index (BMI), systolic blood pressure (SBP), serum high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and fasting blood glucose (FBG), adipokines, and insulin as well as insulin resistance (p < 0.05). Our results confirm that ADIPOQ + 45T > G, LPL PvII, and PGC-1α Gly482Ser loci are associated with MetS in Mongolian subjects.

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Characterization of the ZDSD Rat: A Translational Model for the Study of Metabolic Syndrome and Type 2 Diabetes

Journal of Diabetes Research ◽

10.1155/2015/487816 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 17

Author(s):

Richard G. Peterson ◽

Charles V. Jackson ◽

Karen Zimmerman ◽

Willem de Winter ◽

Norman Huebert ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Metabolic Diseases ◽

Oral Glucose ◽

Glucose Levels ◽

Zdf Rat ◽

Obesity And Diabetes ◽

Elevated Glucose ◽

Polygenic Obesity

Metabolic syndrome and T2D produce significant health and economic issues. Many available animal models have monogenic leptin pathway mutations that are absent in the human population. Development of the ZDSD rat model was undertaken to produce a model that expresses polygenic obesity and diabetes with an intact leptin pathway. A lean ZDF rat with the propensity for beta-cell failure was crossed with a polygenetically obese Crl:CD (SD) rat. Offspring were selectively inbred for obesity and diabetes for >30 generations. In the current study, ZDSD rats were followed for 6 months; routine clinical metabolic endpoints were included throughout the study. In the prediabetic metabolic syndrome phase, ZDSD rats exhibited obesity with increased body fat, hyperglycemia, insulin resistance, dyslipidemia, glucose intolerance, and elevated HbA1c. As disease progressed to overt diabetes, ZDSD rats demonstrated elevated glucose levels, abnormal oral glucose tolerance, increases in HbA1c levels, reductions in body weight, increased insulin resistance with decreasing insulin levels, and dyslipidemia. The ZDSD rat develops prediabetic metabolic syndrome and T2D in a manner that mirrors the development of metabolic syndrome and T2D in humans. ZDSD rats will provide a novel, translational animal model for the study of human metabolic diseases and for the development of new therapies.

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Potential Role of Novel Myokine in Rats-Induced Metabolic Syndrome

Biointerface Research in Applied Chemistry ◽

10.33263/briac123.33053315 ◽

2021 ◽

Vol 12 (3) ◽

pp. 3305-3315

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Potential Role ◽

Serum Levels ◽

Treated Group ◽

Control Group ◽

Standard Diet ◽

The Metabolic Syndrome ◽

Obesity And Diabetes ◽

Increased Risk

One of the main health problems is metabolic syndrome (MetS). Its incidence elevates with age leading to a higher risk of evolving chronic diseases and cancer. Obesity and insulin resistance was considered the most vital components in its pathogenesis for a long time. This study aims to evaluate serum novel adipokine and myokine to establish the irrelation of insulin resistance and their impact on metabolic syndrome. Four groups of rats were included; the control group (C) fed with a standard diet, the second group (CI) fed on a standard diet and injected daily with irisin (100ng/ ml) till the end of the experiment. The third group (MetS group) fed on the HCHF diet for 20 weeks and served as a control group. Rats in the fourth group (MetS+I group) were fed on the HCHF diet until they become obese and diabetic, then injected daily with irisin (100ng/ ml) till the end of the experiment and served as a treated group. Serum levels of obesity and diabetes indices were significantly increased while HDL was significantly decreased in the metabolic syndrome group, but after treatment with irisin, their levels were improved. Both adropin and irisin were significantly decreased, while IL-6 was significantly increased in the same group that was enhanced after irisin treatment. In conclusion, this study demonstrated that lower irisin correlates with the increased risk of increased risk of insulin resistance and MetS. In addition, our results suggested that irisin could have a potential role in glucose metabolism. The relations among increased levels of circulating irisin, insulin resistance, and MetS prevalence may be elucidated with a physiological compensatory contrivance.

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Metabolic Syndrome In Ayurveda & Its Prevention

National Journal of Research in Ayurved Science ◽

10.52482/ayurlog.v6i04.67 ◽

2018 ◽

Vol 6 (04) ◽

Author(s):

Subhash Waghe ◽

Kavita Agrawal

Keyword(s):

Insulin Resistance ◽

Blood Pressure ◽

Metabolic Syndrome ◽

Blood Glucose ◽

High Blood Pressure ◽

Abdominal Fat ◽

Glucose Levels ◽

Waist Size ◽

Blood Glucose Levels ◽

Increased Risk

Metabolic syndrome, refers to a group of conditions common in people with insulin resistance, including higher than normal blood glucose levels, increased waist size due to excess abdominal fat (Obesity), high blood pressure and abnormal levels of cholesterol and triglycerides in the blood. People with metabolic syndrome have an increased risk of developing type 2diabetes and CVD. More than 10 million cases of metabolic syndrome occurs per year in India. The prevalence of metabolic syndrome increases with age and about 40% of people above 60 years are affected with metabolic syndrome. Diabetes occurs as chronic sequel of metabolic syndrome. In the whole world, nearly about 24% of the population is suffering from diabetes. As per WHO, its percentage may go as high as 40-45% in 2020. So, there is intense need to know the graveness of the disease and to understand the possible ways of prevention.

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Metabolic Syndrome During Menopause

Current Vascular Pharmacology ◽

10.2174/1570161116666180904094149 ◽

2019 ◽

Vol 17 (6) ◽

pp. 595-603 ◽

Cited By ~ 4

Author(s):

Sezcan Mumusoglu ◽

Bulent Okan Yildiz

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Central Obesity ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Natural Menopause ◽

The Metabolic Syndrome ◽

Increased Risk ◽

Aging Women

The metabolic syndrome (MetS) comprises individual components including central obesity, insulin resistance, dyslipidaemia and hypertension and it is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The menopause per se increases the incidence of MetS in aging women. The effect(s) of menopause on individual components of MetS include: i) increasing central obesity with changes in the fat tissue distribution, ii) potential increase in insulin resistance, iii) changes in serum lipid concentrations, which seem to be associated with increasing weight rather than menopause itself, and, iv) an association between menopause and hypertension, although available data are inconclusive. With regard to the consequences of MetS during menopause, there is no consistent data supporting a causal relationship between menopause and CVD. However, concomitant MetS during menopause appears to increase the risk of CVD. Furthermore, despite the data supporting the association between early menopause and increased risk of T2DM, the association between natural menopause itself and risk of T2DM is not evident. However, the presence and the severity of MetS appears to be associated with an increased risk of T2DM. Although the mechanism is not clear, surgical menopause is strongly linked with a higher incidence of MetS. Interestingly, women with polycystic ovary syndrome (PCOS) have an increased risk of MetS during their reproductive years; however, with menopausal transition, the risk of MetS becomes similar to that of non-PCOS women.

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Is depression a cause of metabolic abnormality? A European Small State experience

European Journal of Public Health ◽

10.1093/eurpub/ckaa166.1009 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

S Cuschieri

Keyword(s):

Metabolic Syndrome ◽

Cholesterol Level ◽

Fasting Blood Glucose ◽

Depression Symptoms ◽

Health Examination ◽

High Cholesterol ◽

Small State ◽

The Metabolic Syndrome ◽

High Cholesterol Level ◽

Increased Risk

Abstract Background A relationship between depression and metabolic syndrome has been reported. Considering the diabesity rates effecting the small state of Malta it was considered appropriate to explore for links between these diseases, their metabolic determinants with depression. Methods A national health examination survey was conducted. A validated questionnaire note down (1) self-reported depression (2) anti-depressive medication (3) PHQ-9 depression symptoms score (>5 positive for depression). Participants with the presence of one or more of these variables were labelled as having depression. Body mass index (BMI), waist circumference (WC) and blood pressure (BP) were measured. Blood testing for fasting blood glucose (FBG) and lipid profile were performed. The biochemical (FBG, Lipid profiles) and anthropometric profiles (BMI, WC, BP) of the depression population were compared to those without this disease. Univariant and multivariant binary logistic regression models were performed. Results The depression population (17.2% of the total population) had significantly higher median LDL, triglyceride (TG) and total cholesterol (TC) levels when compared to those without the disease (p = <0.01). On univariant modelling each variable (LDL OR:1.15 p = 0.01; TG OR:1.16 p = 0.01; TC OR:1.64 p = <0.01) showed a positive association with having depression even after adjusting for confounding factors (sex, age, education, smoking, alcohol habits). On multivariant modelling only an increase in TC was associated with increased risk of having depression (OR: 1.36 CI95%: 1.05-1.76 p = 0.02) after adjusting for confounders. Conclusions The various components of the metabolic syndrome appeared not to be associated with a diagnosis of depression. Only high cholesterol level exhibited a metabolic link with depression. Although further research is merited, it is suggested that physicians incorporate a depression screening tool as part of their consultation when examining high-risk patients. Key messages A metabolic syndrome profile is not linked with depression. A high cholesterol level is linked with depression, making these individuals susceptible to potential cardiovascular disease.

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