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Sample records for abdominal obesity insulin

  1. Abdominal Obesity and Insulin Resistance in People Exposed to Moderate-to-High Levels of Dioxin.

    PubMed

    Chang, Jung-Wei; Chen, Hsiu-Ling; Su, Huey-Jen; Lee, Ching-Chang

    2016-01-01

    Obesity, a risk factor for developing metabolic complications, is a major public health problem. Abdominal obesity is strongly accompanied by a cluster of metabolic abnormalities characterized by insulin resistance. The link between persistent organic pollutants (POPs) and insulin resistance has been investigated in animal and epidemiological studies. We aimed to examine whether insulin resistance is greater in people with abdominal obesity (AO) and concomitant exposure to serum dioxins (PCDD/Fs). We conducted a cross-sectional descriptive study of 2876 participants living near a PCDD/Fs contaminated area. Seventeen 2,3,7,8-substituted PCDD/Fs congeners were measured, and then the associations between the main predictor variable, serum TEQDF-1998, abdominal obesity (AO), dependent variables, and insulin resistance were examined. Twelve of the 17 congeners, widely distributed among PCDDs, and PCDFs, had trends for associations with abdominal adiposity. In men, the highest quintiles of 1,2,3,7,8-PeCDF; 1,2,3,7,8-PeCDD; 2,3,7,8-TCDD; 2,3,7,8-TCDF; and 2,3,4,7,8-PeCDF had the top five adjusted odds ratios (AORs) + 95% confidence intervals (CIs):[4.2; 2.7-6.4], [3.6; 2.3-5.7], [3.2; 2.1-5.0], [3.0; 2.0-4.5], and [2.9; 1.9-4.7], respectively. In women, the highest quintiles of 1,2,3,4,7,8,9-HpCDF; 1,2,3,6,7,8-HxCDF; and 1,2,3,4,6,7,8-HpCDF had the top three AORs + 95% CIs:[3.0; 1.9-4.7], [2.0; 1.3-3.1], and [1.9; 1.3-2.9], respectively. After confounding factors had been adjusted for, men, but not women, with higher serum TEQDF-1998 levels or abdominal obesity had a significantly (Ptrend < 0.001) greater risk for abnormal insulin resistance. The groups with the highest joint serum TEQDF-1998 and abdominal obesity levels were associated with elevated insulin resistance at 5.0 times the odds of the groups with the lowest joint levels (AOR 5.23; 95% CI: 3.53-7.77). We hypothesize that serum TEQDF-1998 and abdominal obesity affect the association with insulin resistance in

  2. Abdominal Obesity and Insulin Resistance in People Exposed to Moderate-to-High Levels of Dioxin

    PubMed Central

    Chang, Jung-Wei; Chen, Hsiu-Ling; Su, Huey-Jen; Lee, Ching-Chang

    2016-01-01

    Obesity, a risk factor for developing metabolic complications, is a major public health problem. Abdominal obesity is strongly accompanied by a cluster of metabolic abnormalities characterized by insulin resistance. The link between persistent organic pollutants (POPs) and insulin resistance has been investigated in animal and epidemiological studies. We aimed to examine whether insulin resistance is greater in people with abdominal obesity (AO) and concomitant exposure to serum dioxins (PCDD/Fs). We conducted a cross-sectional descriptive study of 2876 participants living near a PCDD/Fs contaminated area. Seventeen 2,3,7,8-substituted PCDD/Fs congeners were measured, and then the associations between the main predictor variable, serum TEQDF-1998, abdominal obesity (AO), dependent variables, and insulin resistance were examined. Twelve of the 17 congeners, widely distributed among PCDDs, and PCDFs, had trends for associations with abdominal adiposity. In men, the highest quintiles of 1,2,3,7,8-PeCDF; 1,2,3,7,8-PeCDD; 2,3,7,8-TCDD; 2,3,7,8-TCDF; and 2,3,4,7,8-PeCDF had the top five adjusted odds ratios (AORs) + 95% confidence intervals (CIs):[4.2; 2.7–6.4], [3.6; 2.3–5.7], [3.2; 2.1–5.0], [3.0; 2.0–4.5], and [2.9; 1.9–4.7], respectively. In women, the highest quintiles of 1,2,3,4,7,8,9-HpCDF; 1,2,3,6,7,8-HxCDF; and 1,2,3,4,6,7,8-HpCDF had the top three AORs + 95% CIs:[3.0; 1.9–4.7], [2.0; 1.3–3.1], and [1.9; 1.3–2.9], respectively. After confounding factors had been adjusted for, men, but not women, with higher serum TEQDF-1998 levels or abdominal obesity had a significantly (Ptrend < 0.001) greater risk for abnormal insulin resistance. The groups with the highest joint serum TEQDF-1998 and abdominal obesity levels were associated with elevated insulin resistance at 5.0 times the odds of the groups with the lowest joint levels (AOR 5.23; 95% CI: 3.53–7.77). We hypothesize that serum TEQDF-1998 and abdominal obesity affect the association with

  3. Abdominal obesity, insulin resistance, and the metabolic syndrome: contribution of physical activity/exercise.

    PubMed

    Ross, Robert; Després, Jean-Pierre

    2009-12-01

    The metabolic syndrome, a constellation of metabolic abnormalities, which include abdominal obesity, insulin resistance, an atherogenic dyslipidemia, elevated blood pressure, a prothrombotic profile, and inflammation is associated with an increased risk of type 2 diabetes (1), cardiovascular disease (2), and mortality (3). The prevalence of individuals with these clustering abnormalities has been steadily increasing over the past two decades, is now estimated to affect at least a quarter of the US population, and is particularly prevalent among older adults (4). Similarly, abdominal obesity, as crudely estimated by an elevated waist circumference, is the most prevalent manifestation of the metabolic syndrome and affects 36% of men and 52% of women, according to the 1999-2000 US National Health and Nutrition Examination Study (5).

  4. Effect of walking exercise on abdominal fat, insulin resistance and serum cytokines in obese women

    PubMed Central

    Hong, Hye-Ryun; Jeong, Jin-Ok; Kong, Ji-Young; Lee, Sang-Hee; Yang, Seung-Hun; Ha, Chang-Duk; Kang, Hyun-Sik

    2014-01-01

    [Purpose] The purpose of the study was to investigate the effect of 12-week walking exercise on abdominal fat, insulin resistance and serum cytokines in obese women. [Methods] Following baseline measurements, obese women (N = 20) who met obesity criterion of BMI at 25 kg/m2 or greater were randomly assigned to the control (n = 10) or exercise groups (n = 10). Women assigned to the exercise group participated in a walking exercise (with an intensity of 50-60% of predetermined VO2max, a frequency of 3 days per week and duration of 50-70 minutes targeting 400 kcal of energy expenditure per session) for 12 weeks, while women assigned to the control group maintained their sedentary lifestyle. After the 12-week walking intervention, post-test measurements were conducted using the same procedure as the baseline measurement. Analyses of variance with repeated measures were used to evaluate any significant time by group interactions for the measured variables. [Results] With respect to body fat parameters, significant time-by-group interactions were found in the abdominal subcutaneous (p = < 0.001) and visceral adipose tissues (p = 0.011). The exercise group had significant reductions in both subcutaneous and visceral adiposity, and the control group had no significant changes in those parameters. Similarly, there were significant time by group interactions in fasting glucose (p = 0.008), HOMA-IR (p = 0.029), serum TNF-α (p = 0.027), and IL-6 (p = 0.048) such that the exercise group had significant reductions in those parameters, with no such significant changes found in the control group. The exercise group also had a significant increase in serum adiponectin (p = 0.002), whereas the control group had no significant change in the parameter. [Conclusion] In summary, the current findings suggest that walking exercise can provide a safe and effective lifestyle strategy against abdominal obesity and serum insulin resistance markers in obese women. PMID:25566464

  5. Effects of aerobic versus resistance exercise without caloric restriction on abdominal fat, intrahepatic lipid, and insulin sensitivity in obese adolescent boys: a randomized, controlled trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The optimal exercise modality for reductions of abdominal obesity and risk factors for type 2 diabetes in youth is unknown. We examined the effects of aerobic exercise (AE) versus resistance exercise (RE) without caloric restriction on abdominal adiposity, ectopic fat, and insulin sensitivity and se...

  6. Insulin differentially modulates the peripheral endocannabinoid system in human subcutaneous abdominal adipose tissue from lean and obese individuals.

    PubMed

    Murdolo, G; Kempf, K; Hammarstedt, A; Herder, C; Smith, U; Jansson, P-A

    2007-09-01

    Human obesity has been associated with a dysregulation of the peripheral and adipose tissue (AT) endocannabinoid system (ES). The aim of this study was to elucidate the acute in vivo effects of insulin on gene expression of the cannabinoid type 1 (CB-1) and type 2 (CB-2) receptors, as well as of the fatty acid amide hydrolase (FAAH) in the sc abdominal adipose tissue (SCAAT). Nine lean (L) and 9 obese (OB), but otherwise healthy males were studied in the fasting state and during a euglycemic hyperinsulinemic clamp (40 mU/m2 * min(-1)). SCAAT biopsies were obtained at baseline and after 270 min of i.v. maintained hyperinsulinemia. The basal SCAAT gene expression pattern revealed an upregulation of the FAAH in the OB (p=0.03 vs L), whereas similar CB-1 and CB-2 mRNA levels were seen. Following hyperinsulinemia, the FAAH mRNA levels significantly increased approximately 2-fold in the L (p=0.01 vs baseline) but not in the OB. In contrast, insulin failed to significantly change both the adipose CB-1 and CB-2 gene expression. Finally, the FAAH gene expression positively correlated with the fasting serum insulin concentration (r 0.66; p=0.01), whereas an inverse association with the whole-body glucose disposal (r -0.58; p<0.05) was seen. Taken together, these first time observations demonstrate that the ES-related genes in the SCAAT differentially respond to hyperinsulinemia in lean/insulin-sensitive and in obese/insulin-resistant individuals. We suggest that insulin may play a key role in the obesity-linked dysregulation of the adipose ES at the gene level.

  7. Abdominal obesity and metabolic syndrome.

    PubMed

    Després, Jean-Pierre; Lemieux, Isabelle

    2006-12-14

    Metabolic syndrome is associated with abdominal obesity, blood lipid disorders, inflammation, insulin resistance or full-blown diabetes, and increased risk of developing cardiovascular disease. Proposed criteria for identifying patients with metabolic syndrome have contributed greatly to preventive medicine, but the value of metabolic syndrome as a scientific concept remains controversial. The presence of metabolic syndrome alone cannot predict global cardiovascular disease risk. But abdominal obesity - the most prevalent manifestation of metabolic syndrome - is a marker of 'dysfunctional adipose tissue', and is of central importance in clinical diagnosis. Better risk assessment algorithms are needed to quantify diabetes and cardiovascular disease risk on a global scale.

  8. Relation between abdominal obesity, insulin resistance and left ventricular hypertrophy diagnosed by electrocardiogram and magnetic resonance imaging in hypertensive patients.

    PubMed

    Vernooij, Joris W P; Cramer, Maarten J M; Visseren, Frank L J; Korndewal, Marjolein J; Bots, Michiel L; Meijs, Matthijs F L; Doevendans, Pieter A F M; Spiering, Wilko

    2012-07-15

    Obesity is related to left ventricular hypertrophy (LVH). Whether LVH on electrocardiography (ECG-LVH) is a result of increased cardiac electrical activity or due to increased left ventricular mass (LVM) remains to be determined. The aims of the present study were to investigate the relation between obesity and ECG-LVH and LVM by magnetic resonance imaging (MRI-LVM) in patients with hypertension and to investigate the relation of insulin resistance (IR) and LVH. Patients with hypertension (n = 421) were evaluated using Sokolow-Lyon voltage, Cornell voltage, and cardiac magnetic resonance imaging. Waist circumference was used as a measure of abdominal obesity. Linear regression analysis revealed an inverse relation (adjusted β = -0.02, 95% confidence interval -0.02 to -0.01) between waist circumference and Sokolow-Lyon voltage, indicating a decrease of 0.02 mV per 1-cm increase in waist circumference. There was a positive relation between waist circumference and MRI-LVM (β = 0.49, 95% confidence interval 0.32 to 0.67). Patients in the highest quartile of LVM had a worse metabolic profile than patients with the Sokolow-Lyon voltage criterion. The relations of IR with ECG-LVH and MRI-LVM were similar to those of waist circumference in relation to ECG-LVH and MRI-LVM. In conclusion, there is an inverse relation between waist circumference and ECG-LVH and a positive relation between waist circumference and MRI-LVM. This study indicates that obesity has a different relation to voltage criteria for LVH compared to anatomic criteria for LVH, supporting the hypothesis that IR decreases electrocardiographic voltages, despite an increase in MRI-LVM. The clinical implication is that especially in patients with IR, Sokolow-Lyon voltage is low in contrast to high MRI-LVM.

  9. Insulin resistance, low cardiorespiratory fitness, and increased exercise blood pressure: contribution of abdominal obesity.

    PubMed

    Huot, Maxime; Arsenault, Benoit J; Gaudreault, Valérie; Poirier, Paul; Pérusse, Louis; Tremblay, Angelo; Bouchard, Claude; Després, Jean-Pierre; Rhéaume, Caroline

    2011-12-01

    Individuals with insulin resistance and low cardiorespiratory fitness are frequently found to have an increased waist circumference and high exercise blood pressure. We tested the hypothesis that the relationships among insulin resistance, low cardiorespiratory fitness, and increased exercise blood pressure may be mediated by an elevated waist circumference. This study included 317 apparently healthy men and women (mean age: 34.8±12.8 years; mean body mass index: 26.1±5.2 kg/m(2)). Exercise blood pressure values were measured using a submaximal ergometer test evaluating physical working capacity. Plasma insulin and glucose levels were measured during a 3-hour oral glucose tolerance test. Multivariate regression analyses showed that waist circumference accounted for 32.8% (P<0.0001) and 45.1% (P<0.0001) of the variance in exercise systolic blood pressure in men and women, respectively. Participants were classified into tertiles according to either insulin response, measured during the oral glucose tolerance test, or fitness levels and then further subdivided into 2 subgroups using sex-specific waist circumference thresholds. Individuals with an increased waist circumference (≥94 cm and ≥80 cm for men and women, respectively) had higher exercise systolic blood pressure compared with individuals with low waist circumference, irrespective of their level of insulin resistance (10.6 versus 6.8, 12.2 versus 7.7, and 13.2 versus 8.7 mm Hg/metabolic equivalent, respectively, for the low, intermediate, and high tertiles; P<0.05) or fitness levels (13.1 versus 8.2, 12.0 versus 7.9, and 10.6 versus 7.1 mm Hg/metabolic equivalent, respectively, for the low, intermediate, and high tertiles; P<0.05). Individuals with a higher waist circumference have elevated exercise systolic blood pressure, regardless of their insulin sensitivity or level of cardiorespiratory fitness.

  10. Impact of weight loss with or without exercise on abdominal fat and insulin resistance in obese individuals: a randomised clinical trial.

    PubMed

    Trussardi Fayh, Ana Paula; Lopes, André Luiz; Fernandes, Pablo Rober; Reischak-Oliveira, Alvaro; Friedman, Rogério

    2013-08-28

    Evidence supports an important contribution of abdominal obesity and inflammation to the development of insulin resistance (IR) and CVD. Weight loss in obese individuals can reduce inflammation and, consequently, IR, but the role of training remains unclear. The aim of this study was to evaluate the effects of body weight reduction with and without exercise over abdominal fat tissue (primary outcome) and IR. In this randomised clinical trial, forty-eight obese individuals (age 31·8 (SD 6·0) years, BMI 34·8 (SD 2·7) kg/m2) were randomised to either a diet-only group (DI) or a diet and exercise group (DI þ EXE). Treatment was maintained until 5% of the initial body weight was lost. At baseline and upon completion, the following parameters were analysed: biochemical parameters such as glycaemia and insulin for the determination of homeostasis model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein (hs-CRP) and abdominal computed tomography for the determination of visceral and subcutaneous adipose tissue. A total of thirteen individuals dropped out before completing the weight-loss intervention and did not repeat the tests. In both the DI (n 18) and DI þ EXE (n 17) groups, we observed significant and similar decreases of visceral adipose tissue (difference between means: 7·9 (95% CI 29·5, 25·2) cm2, P¼0·36), hs-CRP (difference between means: 20·06 (95% CI 20·19, 0·03) mg/l, P¼0·39) and HOMA (difference between means: 20·04 (95% CI 20·17, 0·08), P¼0·53). In the present study, 5% weight loss reduced abdominal fat and IR in obese individuals and exercise did not add to the effect of weight loss on the outcome variables.

  11. HPMC supplementation reduces abdominal fat content, intestinal permeability, inflammation, and insulin resistance in diet-induced obese mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of hydroxypropyl methylcellulose (HPMC), a highly viscous non-fermentable soluble dietary fiber, were evaluated on adipose tissue inflammation and insulin resistance in diet induced obese (DIO) mice fed a high fat (HF) diet supplemented with either HPMC or insoluble fiber. DIO C57BL/6J m...

  12. Association of serum ferritin with insulin resistance, abdominal obesity, and metabolic syndrome in Korean adolescent and adults: The Korean National Health and Nutrition Examination Survey, 2008 to 2011.

    PubMed

    Shim, Young Suk; Kang, Min Jae; Oh, Yeon Jeong; Baek, Joon Woo; Yang, Seung; Hwang, Il Tae

    2017-02-01

    This study aimed to evaluate the associations of serum ferritin with insulin resistance indices, body fat mass/percentage, and all the components of metabolic syndrome (MetS), as well as the risk for MetS according to serum ferritin levels in Korean adolescents and adults.A total of 15,963 Korean males and females aged 16 to 80 years were analyzed using data from the Korean National Health and Nutrition Examination Survey, 2005 to 2011.The median serum ferritin concentration was 98.82 ng/mL for males and 38.60 ng/mL for females (P < 0.001). Increased risks of greater waist circumference and elevated glucose levels, elevated triglyceride levels, and reduced high-density lipoprotein cholesterol levels were noted across the serum ferritin quartiles after adjustment for confounders in both genders (P ≤ 0.012 for trend). Insulin resistance indices and abdominal obesity (trunk fat mass/percent) increased across the ferritin concentration quartiles after adjustment for confounders in males and females (P ≤ 0.011 for trend), and the risk of MetS increased across the ferritin quartiles in males (P < 0.001 for trend) and females (P = 0.001 for trend). The highest serum ferritin quartile exhibited a 1.62-fold increased risk of MetS (95% CI, 1.28-2.12) in males and a 1.36-fold increased risk of MetS (95% CI, 1.09-1.69) in females compared with the lowest quartile after adjustment for confounders.Our results suggest that ferritin is associated with insulin resistance and abdominal obesity.

  13. The link between abdominal obesity and the metabolic syndrome.

    PubMed

    Phillips, Liza K; Prins, Johannes B

    2008-04-01

    The clustering of cardiovascular risk factors associated with abdominal obesity is well established. Although currently lacking a universal definition, the metabolic syndrome describes a constellation of metabolic abnormalities, including abdominal obesity, and was originally introduced to characterize a population at high cardiovascular risk. Adipose tissue is a dynamic endocrine organ that secretes several inflammatory and immune mediators known as adipokines. Dysregulation of adipokine secretion, free fatty acid toxicity, and the site-specific differences in abdominal (visceral) versus subcutaneous fat support abdominal obesity as a causal factor mediating the insulin resistance, increased risk of diabetes, and cardiovascular disease in the metabolic syndrome.

  14. [METHODS IN ABDOMINAL OBESITY].

    PubMed

    Savchenko, O; Zavalskaya, T; Lizogub, V; Kuzhel, O; Baitser, M; Zapeka, Y

    2015-01-01

    This article describes the anatomical and physiological, histological and topographic features of adipose tissue on the relationship of metabolic syndrome, insulin resistance and cardiovascular disease. An advanced diagnostic techniques of total body fat and visceral fat content quantification as the most metabolically active are described.

  15. Factors associated with abdominal obesity in children

    PubMed Central

    Melzer, Matheus Ribeiro Theodósio Fernandes; Magrini, Isabella Mastrangi; Domene, Semíramis Martins Álvares; Martins, Paula Andrea

    2015-01-01

    Objective: To identify the association of dietary, socioeconomic factors, sedentary behaviors and maternal nutritional status with abdominal obesity in children. Methods: A cross-sectional study with household-based survey, in 36 randomly selected census tracts in the city of Santos, SP. 357 families were interviewed and questionnaires and anthropometric measurements were applied in mothers and their 3-10 years-old children. Assessment of abdominal obesity was made by maternal and child's waist circumference measurement; for classification used cut-off points proposed by World Health Organization (1998) and Taylor et al. (2000) were applied. The association between variables was performed by multiple logistic regression analysis. Results: 30.5% of children had abdominal obesity. Associations with children's and maternal nutritional status and high socioeconomic status were shown in the univariate analysis. In the regression model, children's body mass index for age (OR=93.7; 95%CI 39.3-223.3), female gender (OR=4.1; 95%CI 1.8-9.3) and maternal abdominal obesity (OR=2.7; 95%CI 1.2-6.0) were significantly associated with children's abdominal obesity, regardless of the socioeconomic status. Conclusions: Abdominal obesity in children seems to be associated with maternal nutritional status, other indicators of their own nutritional status and female gender. Intervention programs for control of childhood obesity and prevention of metabolic syndrome should consider the interaction of the nutritional status of mothers and their children. PMID:26298655

  16. Physical activity and abdominal obesity in youth.

    PubMed

    Kim, YoonMyung; Lee, SoJung

    2009-08-01

    Childhood obesity continues to escalate despite considerable efforts to reverse the current trends. Childhood obesity is a leading public health concern because overweight-obese youth suffer from comorbidities such as type 2 diabetes mellitus, nonalcoholic fatty liver disease, metabolic syndrome, and cardiovascular disease, conditions once considered limited to adults. This increasing prevalence of chronic health conditions in youth closely parallels the dramatic increase in obesity, in particular abdominal adiposity, in youth. Although mounting evidence in adults demonstrates the benefits of regular physical activity as a treatment strategy for abdominal obesity, the independent role of regular physical activity alone (e.g., without calorie restriction) on abdominal obesity, and in particular visceral fat, is largely unclear in youth. There is some evidence to suggest that, independent of sedentary activity levels (e.g., television watching or playing video games), engaging in higher-intensity physical activity is associated with a lower waist circumference and less visceral fat. Several randomized controlled studies have shown that aerobic types of exercise are protective against age-related increases in visceral adiposity in growing children and adolescents. However, evidence regarding the effect of resistance training alone as a strategy for the treatment of abdominal obesity is lacking and warrants further investigation.

  17. Association of obesity and leptin with insulin resistance in type 2 diabetes mellitus in Indian population.

    PubMed

    Das, Piyali; Bhattacharjee, Debojyoti; Bandyopadhyay, Subir Kumar; Bhattacharya, Gorachand; Singh, Ramji

    2013-01-01

    Obesity and diabetes mellitus are two modern epidemics. But their interrelationship is debated. Here we explored the probable association among obesity, leptin and insulin resistance in type 2 diabetes mellitus. 60 recent onset (< 5 years) diabetics and age-sex matched 33 non diabetic controls were assessed for physical and chemical parameters like Body Mass Index, abdominal circumference, waist/hip ratio, fasting blood glucose, insulin and leptin. Degree of insulin resistance was calculated by HOMA-IR method (Homeostatic Model Assessment). All the physical parameters showed positive correlation with leptin and the HOMA-IR score, strength of association being highest between insulin resistance and abdominal circumference. Leptin and insulin resistance showed no correlation. Findings were lower in controls. Study concluded that, obesity mainly central type might be responsible for insulin resistance in type 2 diabetes mellitus where as leptin, a potential marker for obesity, may not. This perhaps points towards the multifactorial causation of insulin resistance in type 2 diabetes mellitus.

  18. Metabolic syndrome and insulin resistance in obese adolescents

    PubMed Central

    Gobato, Amanda Oliva; Vasques, Ana Carolina J.; Zambon, Mariana Porto; Barros, Antonio de Azevedo; Hessel, Gabriel

    2014-01-01

    Objective: To verify the prevalence of metabolic syndrome and insulin resistance in obese adolescents and its relationship with different body composition indicators. Methods: A cross-sectional study comprising 79 adolescents aged ten to 18 years old. The assessed body composition indicators were: body mass index (BMI), body fat percentage, abdominal circumference, and subcutaneous fat. The metabolic syndrome was diagnosed according to the criteria proposed by Cook et al. The insulin resistance was determined by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index for values above 3.16. The analysis of ROC curves was used to assess the BMI and the abdominal circumference, aiming to identify the subjects with metabolic syndrome and insulin resistance. The cutoff point corresponded to the percentage above the reference value used to diagnose obesity. Results: The metabolic syndrome was diagnosed in 45.5% of the patients and insulin resistance, in 29.1%. Insulin resistance showed association with HDL-cholesterol (p=0.032) and with metabolic syndrome (p=0.006). All body composition indicators were correlated with insulin resistance (p<0.01). In relation to the cutoff point evaluation, the values of 23.5 and 36.3% above the BMI reference point allowed the identification of insulin resistance and metabolic syndrome. The best cutoff point for abdominal circumference to identify insulin resistance was 40%. Conclusions: All body composition indicators, HDL-cholesterol and metabolic syndrome showed correlation with insulin resistance. The BMI was the most effective anthropometric indicator to identify insulin resistance. PMID:24676191

  19. Abdominal Obesity and Metabolic Syndrome Burden in Adolescents-Penn State Children Cohort Study

    PubMed Central

    He, Fan; Rodriguez-Colon, Sol; Fernandez-Mendoza, Julio; Vgontzas, Alexandros N.; Bixler, Edward O.; Berg, Arthur; Kawasawa, Yuka Imamura; Sawyer, Marjorie D.; Liao, Duanping

    2014-01-01

    INTRODUCTION To investigate the association between abdominal obesity and metabolic syndrome (MetS) burden in a population-based sample of adolescents. METHODS We used the data from 421 adolescents who completed the follow-up examination in the Penn State Children Cohort study. Dual-energy x-ray absorptiometry (DXA) was used to assess abdominal obesity, as measured by android/gynoid fat ratio (A/G ratio), android/whole body fat proportion (A/W proportion), visceral (VAT) and subcutaneous fat (SAT) areas. Continuous metabolic syndrome score (cMetS), calculated as the sum of the age and sex-adjusted standardized residual (Z-score) of five established MetS components, was used to assess the MetS burden. Linear regression models were used to analyze the impact of DXA measures on cMetS and individual cMetS components. All models were adjusted for age, race, sex, and general obesity. RESULTS Abdominal obesity is significantly associated with increased cMetS. With 1 standard deviation (SD) increase in A/G ratio, A/W proportion, VAT area, and SAT area, cMetS increased by 1.34 (SE=0.17), 1.25 (SE=0.19), 1.67 (SE=0.17), and 1.84 (SE=0.20) units, respectively. At individual component level, strongest association was observed between abdominal obesity and insulin resistance than lipid-based or blood pressure-based components. VAT and SAT had a stronger impact on insulin resistance than android ratio-based DXA measurements. CONCLUSIONS Abdominal obesity is associated with higher MetS burden in adolescent population. The association between abdominal obesity and insulin resistance measure is the strongest, suggesting the key impact of abdominal obesity on insulin resistance in adolescents Mets burden. PMID:25220887

  20. A randomized, double blind, cross-over, placebo-controlled clinical trial to assess the effects of Candesartan on the insulin sensitivity on non diabetic, non hypertense subjects with dysglyce mia and abdominal obesity. "ARAMIA"

    PubMed Central

    López-Jaramillo, Patricio; Pradilla, Lina P; Lahera, Vicente; Sieger, Federico A Silva; Rueda-Clausen, Christian F; Márquez, Gustavo A

    2006-01-01

    Candesartan, could improve the HOMA index, the response to the oral glucose tolerance test and reduce the plasma levels of adipoquines, oxidative stress and prothrombotic markers, in non diabetic, non hypertense subjects with dysglycemia and abdominal obesity, recruited from a population at high risk of developing insulin resistance. These effects are independent of the changes in arterial blood pressure. Trial registration: NCT00319202 PMID:16959033

  1. Association of Oxidative Stress and Obesity with Insulin Resistance in Type 2 Diabetes Mellitus.

    PubMed

    Das, P; Biswas, S; Mukherjee, S; Bandyopadhyay, S K

    2016-01-01

    Oxidative stress occurs due to delicate imbalance between pro-oxidant and anti oxidant forces in our system. It has been found to be associated with many morbidities but its association with obesity and insulin resistance is still controversial. Here in our study we examined 167 patients of recent onset type 2 diabetes mellitus and 60 age sex matched non-diabetic control. Body Mass Index (BMI), abdominal circumference, fasting blood glucose, serum insulin and plasma Malondealdehyde (MDA, marker for oxidative stress) were measured in them. On the basis of BMI, subjects were divided into obese (BMI≥25) and non obese (BMI<25) groups. Insulin resistance scores were calculated by Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) method. Physical parameters (BMI, abdominal circumference) as well as levels of insulin and MDA were found to be significantly higher in subjects with diabetes than their non diabetic controls. The said parameters also showed significant difference in obese and non-obese sub groups. Insulin resistance score showed positive correlation with BMI, abdominal circumference, and plasma MDA, strength of association being highest with abdominal circumference. Plasma MDA was found to have positive correlation with physical parameters. Study concludes that, obesity mainly central type may predispose to insulin resistance and oxidative stress may be a crucial factor in its pathogenesis. Thus, oxidative stress may be the connecting link between obesity and type 2 diabetes mellitus, two on going global epidemics.

  2. Abdominal Obesity, Race and Chronic Kidney Disease in Young Adults: Results from NHANES 1999-2010

    PubMed Central

    Sarathy, Harini; Henriquez, Gabriela; Abramowitz, Matthew K.; Kramer, Holly; Rosas, Sylvia E.; Johns, Tanya; Kumar, Juhi; Skversky, Amy; Kaskel, Frederick; Melamed, Michal L.

    2016-01-01

    Objective Kidney dysfunction in obesity may be independent of and may precede the development of hypertension and/or diabetes mellitus. We aimed to examine if abdominal obesity is associated with early markers of CKD in a young healthy population and whether these associations differ by race and/or ethnicity. Methods We analyzed data from the NHANES 1999–2010 for 6918 young adults ages 20–40 years. Abdominal obesity was defined by gender criteria of waist circumference. CKD markers included estimated glomerular filtration rate and albuminuria ≥30 mg/g. Race stratified analyses were done overall and in subgroups with normal blood pressures, normoglycemia and normal insulin sensitivity. Awareness of CKD was assessed in participants with albuminuria. Results Abdominal obesity was present in over one-third of all young adults and was more prevalent among non-Hispanic blacks (45.4%) versus Mexican-Americans (40.6%) or non-Hispanic whites (37.4%) (P-value = 0.004). Mexican-American young adults with abdominal obesity had a higher odds of albuminuria even among those with normal blood pressure, normal glucose, and normal insulin sensitivity [adjusted odds ratio 4.5; 95% confidence interval (1.6–12.2), p = 0.004]. Less than 5% of young adults with albuminuria of all races and ethnicities had been told they had kidney disease. Conclusion Abdominal obesity in young adults, especially in Mexican-Americans, is independently associated with albuminuria even with normal blood pressures, normoglycemia and normal insulin levels. Greater awareness of CKD is needed to protect this young population from long-standing exposure to abdominal obesity and early progressive renal disease. PMID:27224643

  3. Mechanisms of insulin resistance in obesity.

    PubMed

    Ye, Jianping

    2013-03-01

    Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy.

  4. Abdominal obesity and metabolic syndrome burden in adolescents--Penn State Children Cohort study.

    PubMed

    He, Fan; Rodriguez-Colon, Sol; Fernandez-Mendoza, Julio; Vgontzas, Alexandros N; Bixler, Edward O; Berg, Arthur; Imamura Kawasawa, Yuka; Sawyer, Marjorie D; Liao, Duanping

    2015-01-01

    To investigate the association between abdominal obesity and metabolic syndrome (MetS) burden in a population-based sample of adolescents, we used data from 421 adolescents who completed the follow-up examination in the Penn State Children Cohort study. Dual-energy x-ray absorptiometry (DXA) was used to assess abdominal obesity, as measured by android/gynoid fat ratio (A/G ratio), android/whole body fat proportion (A/W proportion), visceral (VAT) and subcutaneous fat (SAT) areas. Continuous metabolic syndrome score (cMetS), calculated as the sum of the age and sex-adjusted standardized residual (Z-score) of five established MetS components, was used to assess the MetS burden. Linear regression models were used to analyze the impact of DXA measures on cMetS components. All models were adjusted for age, race, sex, and general obesity. We found abdominal obesity is significantly associated with increased cMetS. With 1 standard deviation (SD) increase in A/G ratio, A/W proportion, VAT area, and SAT area, cMetS increased by 1.34 (SE=0.17), 1.25 (SE=0.19), 1.67 (SE=0.17), and 1.84 (SE=0.20) units, respectively. At individual component level, strongest association was observed between abdominal obesity and insulin resistance (IR) than lipid-based or blood pressure-based components. VAT and SAT had a stronger impact on IR than android ratio-based DXA measurements. In conclusion, abdominal obesity is associated with higher MetS burden in adolescent population. The association between abdominal obesity and IR measure is the strongest, suggesting the key impact of abdominal obesity on IR in adolescents MetS burden.

  5. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk.

    PubMed

    Després, Jean-Pierre; Lemieux, Isabelle; Bergeron, Jean; Pibarot, Philippe; Mathieu, Patrick; Larose, Eric; Rodés-Cabau, Josep; Bertrand, Olivier F; Poirier, Paul

    2008-06-01

    There is currently substantial confusion between the conceptual definition of the metabolic syndrome and the clinical screening parameters and cut-off values proposed by various organizations (NCEP-ATP III, IDF, WHO, etc) to identify individuals with the metabolic syndrome. Although it is clear that in vivo insulin resistance is a key abnormality associated with an atherogenic, prothrombotic, and inflammatory profile which has been named by some the "metabolic syndrome" or by others "syndrome X" or "insulin resistance syndrome", it is more and more recognized that the most prevalent form of this constellation of metabolic abnormalities linked to insulin resistance is found in patients with abdominal obesity, especially with an excess of intra-abdominal or visceral adipose tissue. We have previously proposed that visceral obesity may represent a clinical intermediate phenotype reflecting the relative inability of subcutaneous adipose tissue to act as a protective metabolic sink for the clearance and storage of the extra energy derived from dietary triglycerides, leading to ectopic fat deposition in visceral adipose depots, skeletal muscle, liver, heart, etc. Thus, visceral obesity may partly be a marker of a dysmetabolic state and partly a cause of the metabolic syndrome. Although waist circumference is a better marker of abdominal fat accumulation than the body mass index, an elevated waistline alone is not sufficient to diagnose visceral obesity and we have proposed that an elevated fasting triglyceride concentration could represent, when waist circumference is increased, a simple clinical marker of excess visceral/ectopic fat. Finally, a clinical diagnosis of visceral obesity, insulin resistance, or of the metabolic syndrome is not sufficient to assess global risk of cardiovascular disease. To achieve this goal, physicians should first pay attention to the classical risk factors while also considering the additional risk resulting from the presence of abdominal

  6. IMPACT OF ABDOMINAL OBESITY ON INCIDENCE OF ADVERSE METABOLIC EFFECTS ASSOCIATED WITH ANTIHYPERTENSIVE MEDICATIONS

    PubMed Central

    Cooper-DeHoff, Rhonda M.; Wen, Sheron; Beitelshees, Amber L.; Zineh, Issam; Gums, John G.; Turner, Stephen T.; Gong, Yan; Hall, Karen; Parekh, Vishal; Chapman, Arlene B.; Boerwinkle, Eric; Johnson, Julie A.

    2009-01-01

    We assessed adverse metabolic effects (AMEs) of atenolol and hydrochlorothiazide (HCTZ) among hypertensive patients with and without abdominal obesity using data from a randomized, open-label study of hypertensive patients without evidence of cardiovascular disease or diabetes. Intervention included randomization to HCTZ 25mg or atenolol 100mg monotherapy followed by their combination. Fasting glucose, insulin, triglycerides, HDL cholesterol and uric acid were measured at baseline and after mono-and combination therapy. Outcomes included new occurrence of and predictors for new cases of glucose ≥ 100mg/dl (impaired fasting glucose [IFG]), triglyceride ≥ 150 mg/dl, HDL ≤ 40mg/dl for men or ≤ 50mg/dl for women, or new onset diabetes according to presence or absence of abdominal obesity. Abdominal obesity was present in 167/395 (58%). Regardless of strategy, in those with abdominal obesity, 20% had IFG at baseline compared with 40% at end of study (p<0.0001). Proportion with triglycerides ≥ 150 mg/dl increased from 33% at baseline to 46% at end of study (p<0.01). New onset diabetes occurred in 13 (6%) with and in 4 (2%) without abdominal obesity. Baseline levels of glucose, triglyceride and HDL predicted adverse outcomes and predictors for new onset diabetes after monotherapy in those with abdominal obesity included HCTZ strategy (OR 47, 95% CI 2.55-862), female sex (OR 31.3, 95% CI 2.10-500) and uric acid (OR 3.2, 95% CI 2.35-7.50). Development of AME, including new onset diabetes associated with short term exposure to HCTZ and atenolol was more common in those with abdominal obesity. PMID:19917874

  7. Insulin resistance is associated with gallstones even in non-obese, non-diabetic Korean men.

    PubMed

    Chang, Yoosoo; Sung, Eunju; Ryu, Seungho; Park, Yong-Woo; Jang, Yu Mi; Park, Minseon

    2008-08-01

    It remains unclear as to whether insulin resistance alone or in the presence of wellknown risk factors, such as diabetes or obesity, is associated with gallstones in men. The aim of this study was to determine whether insulin resistance is associated independently with gallstone disease in non-diabetic men, regardless of obesity. Study subjects were 19,503 Korean men, aged 30-69 yr, with fasting blood glucose level <126 mg/dL and without a documented history of diabetes. Gallbladder status was assessed via abdominal ultrasonography after overnight fast. Body mass index and waist circumference were measured. Insulin resistance was estimated by the Homeostasis Model Assessment of insulin resistance (HOMA-IR). The prevalence of obesity, abdominal obesity, and metabolic syndrome in the subjects with gallstones were higher than in those without. The prevalence of elevated HOMA (>75 percentile) in subjects with gallstones was significantly higher than in those without, and this association remained even after the obesity stratification was applied. In multiple logistic regression analyses, only age and HOMA proved to be independent predictors of gallstones. Insulin resistance was positively associated with gallstones in non-diabetic Korean men, and this occurred regardless of obesity. Gallstones appear to be a marker for insulin resistance, even in non-diabetic, nonobese men.

  8. Risk factors associated with the metabolic syndrome in abdominal obesity.

    PubMed

    Schneider, H J; Klotsche, J; Friedrich, N; Schipf, S; Völzke, H; Silber, S; März, W; Nauck, M; Pittrow, D; Wehling, M; Sievers, C; Lehnert, H; Stalla, G K; Wittchen, H-U; Wallaschofski, H

    2012-10-01

    Obesity is associated with the metabolic syndrome. However, not all obese individuals have cardiovascular risk factors (CVRF). It is not clear how many abdominally obese individuals are free of CVRF and what distinguishes them from the group of obese individuals with CVRF. In this study, we aimed to assess the associated factors and prevalence of abdominal obesity without CVRF. In our cross-sectional analysis, we included n = 4244 subjects from the Study of Health in Pomerania (SHIP), a population-based study and n = 6671 subjects from the Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment (DETECT) study, a representative primary care study in Germany. We defined abdominal obesity by waist-to-height ratio (WHtR) of 0.5 or greater. We assessed how many subjects with abdominal obesity had CVRF based on the definition of the metabolic syndrome. We analysed which conditions were associated with the absence of CVRF in abdominal obesity. In SHIP and DETECT, 2652 (62.5%) and 5126 (76.8%) subjects had a WHtR ≥ 0.5. Among those with a WHtR ≥ 0.5, 9.0% and 13.8% were free of CVRF and 49.9% and 52.7% had at least two CVRF in SHIP and DETECT, respectively. In both studies, after backward elimination, age, male sex, body mass index and high liver enzymes and unemployment were consistently inversely associated with the absence of CVRF. Among abdominally obese subjects, the prevalence of metabolically healthy subjects is low. Conditions consistently associated with the absence of CVRF in abdominal obesity are younger age, female sex, low BMI, and normal liver enzymes, the latter likely reflecting the absence of steatohepatitis.

  9. Evaluation of the impact of abdominal obesity on glucose and lipid metabolism disorders in adults with Down syndrome.

    PubMed

    Real de Asua, Diego; Parra, Pedro; Costa, Ramón; Moldenhauer, Fernando; Suarez, Carmen

    2014-11-01

    We aimed to describe anthropometric differences in weight-related disorders between adults with Down syndrome (DS) and healthy controls, as well as their disparate impact on glucose and lipid metabolism disorders. We underwent a cross-sectional study of 49 consecutively selected, community-residing adults with DS and 49 healthy controls in an outpatient clinic of a tertiary care hospital in Madrid, Spain. Siblings of adults with DS were studied as controls in 42 cases. Epidemiological data (age and gender), anthropometric data (body mass index, waist circumference, and waist-to-height ratio [WHR]), coexisting clinical conditions, and laboratory data (fasting glucose, insulin, glycated hemoglobin, creatinine, thyroid hormones, and lipid profile) were measured and compared between the groups. Adults with DS were significantly younger and more often male, with a higher prevalence of overweight and obesity than controls. Adults with DS also had a higher WHR, and more frequently presented abdominal obesity. Moreover, insulin resistance measured using the homeostatic model assessment was more prevalent among adults with DS and abdominal obesity. However, lipid profiles were similar between groups. The kappa correlation index for the diagnosis of abdominal obesity between waist circumference and WHR was 0.24 (95%CI: 0.13-0.34). We concluded that the prevalence of overweight, obesity, and abdominal obesity was higher in adults with DS than in controls. Adults with DS and abdominal obesity showed higher indexes of insulin resistance than their non-obese peers. WHR was a useful tool for the evaluation of abdominal obesity in this population.

  10. Obesity and insulin resistance associated with lower plasma vitamin B12 in PCOS.

    PubMed

    Kaya, Cemil; Cengiz, Sevim Dinçer; Satiroğlu, Hakan

    2009-11-01

    Polycystic ovary syndrome (PCOS) shares some or most components of metabolic cardiovascular syndrome, manifested by abdominal obesity, insulin resistance, dyslipidaemia and atherosclerosis. It has been previously demonstrated that folate and vitamin B(12) treatment improved insulin resistance in patients with metabolic syndrome. This study first investigated whether PCOS patients have lower or higher vitamin B(12), folate and homocysteine concentrations when compared with healthy, age and body mass index matched controls, and, then examined associations between vitamin B(12), folate, homocysteine and insulin resistance and obesity in PCOS patients. Homocysteine concentrations and homeostasis model assessment index were higher, whereas concentrations of vitamin B(12) were lower in PCOS patients with insulin resistance compared with those without insulin resistance. Serum vitamin B(12) concentrations were significantly lower in obese PCOS women in comparison with obese control women (P < 0.05). Fasting insulin, insulin resistance and homocysteine are independent determinants of serum vitamin B(12) concentrations in PCOS patients. Insulin resistance, obesity, and elevated homocysteine were associated with lower serum vitamin B(12) concentrations in PCOS patients.

  11. Optimal waist circumference cutoff values for the diagnosis of abdominal obesity in korean adults.

    PubMed

    Yoon, Yeong Sook; Oh, Sang Woo

    2014-12-29

    Abdominal obesity is associated closely with insulin resistance, diabetes, and cardiovascular disease. Waist circumference (WC) is a useful surrogate marker commonly used for abdominal adiposity. The determination of WC cutoff levels is important in the prevention and treatment of obesity, type 2 diabetes, and related cardiovascular diseases. Recent epidemiological evidence suggested that appropriate optimal cutoffs for Koreans ranged over 80 to 89.8 cm in males and 76.1 to 86.5 cm in females. We analyzed the data from two large cohorts using receiver operating characteristic curve analysis with the incidences of diabetes, hypertension, dyslipidemia, cerebrovascular disease, myocardial infarct, angina, coronary artery disease, and multiple metabolic risk factors as outcome variables. Optimal WC cutoff points for Koreans were 85 cm in males and 80 cm in females. However, considering the prevalence of abdominal obesity and the health costs for its prevention and management, 90 cm in males and 85 cm in females are probably more appropriate thresholds for abdominal obesity. These values may be modified once better research is performed through prospective studies using representative populations, common health outcomes, and proper analytical approaches.

  12. Interaction between corticosterone and insulin in obesity: regulation of lard intake and fat stores.

    PubMed

    la Fleur, Susanne E; Akana, Susan F; Manalo, Sotara L; Dallman, Mary F

    2004-05-01

    Passive elevations in glucocorticoids result in increased insulin and abdominal obesity with peripheral wasting, as observed in Cushing's syndrome, with little effect on chow intake. In the absence of insulin (streptozotocin-induced diabetes) diabetic rats markedly increase their chow intake in proportion to glucocorticoids. Given a choice of lard or chow, diabetic rats first eat lard, then reduce caloric intake to normal for 48 h before returning to hyperphagia on chow alone. We performed three experiments to determine the relationship of corticosterone and insulin to lard intake, chow intake, body weight, hormones, and fat depots. The results of these studies clarify the actions of both circulating glucocorticoids and insulin on caloric intake in adult male rats. Our experiments show that glucocorticoids provoke dose-related increases in total caloric intake that persist for days and weeks; the results also suggest that increasing insulin concentrations stimulated by glucocorticoids determine the amount of fat intake. Furthermore, we show that lard intake is associated with increasing insulin concentrations. Additionally, the results in adrenalectomized and adrenalectomized, streptozotocin-induced diabetic rats strongly suggest that it is a combination of corticosterone and insulin that increases abdominal fat depot weight. Independently of the hormonally manipulated rats, the results also show that intact rats voluntarily eat a considerable and stable proportion of their daily calories as lard when given a choice between lard and chow. These results suggest that some human obesities may result from elevated glucocorticoids and insulin increasing the proportional intake of high density calories.

  13. Waist circumference and cardiorespiratory fitness are independently associated with glucose tolerance and insulin resistance in obese women.

    PubMed

    Shalev-Goldman, Einat; McGuire, K Ashlee; Ross, Robert

    2014-03-01

    The purpose of this study was to determine the independent associations between physical activity (PA), cardiorespiratory fitness (CRF), abdominal obesity and insulin action in obese women. We studied 141 abdominally obese women (waist circumference (WC): 106.4 ± 10.2 cm). PA duration (min/day) and intensity (counts/min) were obtained by accelerometry. CRF was measured using a treadmill. WC was measured at the iliac crest; abdominal adiposity was measured by magnetic resonance imaging. Glucose and insulin measures were obtained during a 75-g, 2-h glucose tolerance test. The homeostasis model of assessment iHOMA2-IS was used to estimate insulin sensitivity. PA duration and intensity were not associated with glucose or insulin metabolism (p > 0.05). However, moderate-to-vigorous PA (MVPA) duration was associated with fasting insulin and iHOMA2-IS (p < 0.01). CRF was associated with fasting insulin and iHOMA2-IS (r = 0.27, p ≤ 0.01), whereas WC was associated with fasting insulin (r = 0.50, p < 0.01) and iHOMA2-IS (r = -0.52, p ≤ 0.01). Following adjustment for CRF, MVPA, and age, WC remained associated with fasting glucose, insulin, 2-h glucose and iHOMA2-IS (r = -0.44, p ≤ 0.01). CRF was associated with fasting glucose as well as 1- and 2-h glucose (r = 0.24, p < 0.01) after adjusting for WC, MVPA, and age. MVPA was not associated with glucose or insulin measures after control for CRF and WC (p > 0.05). Mediation analysis revealed that CRF and WC combined mediated the relationship between MVPA and both glucose tolerance and insulin resistance (p < 0.05). In conclusion, among abdominally obese women, WC and CRF are independently associated with measures of glucose tolerance and insulin resistance and mediate the association between MVPA and insulin resistance.

  14. Increased insulin translation from an insulin splice-variant overexpressed in diabetes, obesity, and insulin resistance.

    PubMed

    Minn, Alexandra H; Lan, Hong; Rabaglia, Mary E; Harlan, David M; Peculis, Brenda A; Attie, Alan D; Shalev, Anath

    2005-03-01

    Type 2 diabetes occurs when pancreatic beta-cells become unable to compensate for the underlying insulin resistance. Insulin secretion requires beta-cell insulin stores to be replenished by insulin biosynthesis, which is mainly regulated at the translational level. Such translational regulation often involves the 5'-untranslated region. Recently, we identified a human insulin splice-variant (SPV) altering only the 5'-untranslated region and conferring increased translation efficiency. We now describe a mouse SPV (mSPV) that is found in the cytoplasm and exhibits increased translation efficiency resulting in more normal (prepro)insulin protein per RNA. The RNA stability of mSPV is not increased, but the predicted secondary RNA structure is altered, which may facilitate translation. To determine the role of mSPV in insulin resistance and diabetes, mSPV expression was measured by quantitative real-time RT-PCR in islets from three diabetic and/or insulin-resistant, obese and nonobese, mouse models (BTBRob/ob, C57BL/6ob/ob, and C57BL/6azip). Interestingly, mSPV expression was significantly higher in all diabetic/insulin-resistant mice compared with wild-type littermates and was dramatically induced in primary mouse islets incubated at high glucose. This raises the possibility that the mSPV may represent a compensatory beta-cell mechanism to enhance insulin biosynthesis when insulin requirements are elevated by hyperglycemia/insulin resistance.

  15. Cardiovascular disease risk of abdominal obesity vs. metabolic abnormalities.

    PubMed

    Wildman, Rachel P; McGinn, Aileen P; Lin, Juan; Wang, Dan; Muntner, Paul; Cohen, Hillel W; Reynolds, Kristi; Fonseca, Vivian; Sowers, MaryFran R

    2011-04-01

    It remains unclear whether abdominal obesity increases cardiovascular disease (CVD) risk independent of the metabolic abnormalities that often accompany it. Therefore, the objective of this study was to evaluate the independent effects of abdominal obesity vs. metabolic syndrome and diabetes on the risk for incident coronary heart disease (CHD) and stroke. The Framingham Offspring, Atherosclerosis Risk in Communities, and Cardiovascular Health studies were pooled to assess the independent effects of abdominal obesity (waist circumference >102 cm for men and >88 cm for women) vs. metabolic syndrome (excluding the waist circumference criterion) and diabetes on risk for incident CHD and stroke in 20,298 men and women aged ≥45 years. The average follow-up was 8.3 (s.d. 1.9) years. There were 1,766 CVD events. After adjustment for demographic factors, smoking, alcohol intake, number of metabolic syndrome components, and diabetes, abdominal obesity was not significantly associated with an increased risk of CVD (hazard ratio (HR) (95% confidence interval): 1.09 (0.98, 1.20)). However, after adjustment for demographics, smoking, alcohol intake, and abdominal obesity, having 1-2 metabolic syndrome components, the metabolic syndrome and diabetes were each associated with a significantly increased risk of CVD (2.12 (1.80, 2.50), 2.82 (1.92, 4.12), and 5.33 (3.37, 8.41), respectively). Although abdominal obesity is an important clinical tool for identification of individuals likely to possess metabolic abnormalities, these data suggest that the metabolic syndrome and diabetes are considerably more important prognostic indicators of CVD risk.

  16. Role of human lipocalin proteins in abdominal obesity after acute pancreatitis.

    PubMed

    Singh, Ruma G; Pendharkar, Sayali A; Plank, Lindsay D; Petrov, Maxim S

    2017-03-07

    Lipocalin proteins are small regulatory peptides implicated in metabolism, inflammation, and immunity. Although lipocalin proteins have been linked to various clinical conditions, their role in the acute inflammatory setting, such as acute pancreatitis (AP), has only been sparsely investigated. Two members of the lipocalin family, lipocalin-2 (LCN-2) and retinol binding protein -4 (RBP-4), play an important role in obesity and insulin resistance. In this study, we analysed circulating levels of LCN-2 and RBP-4 in 92 individuals after AP, of whom 41 individuals had abdominal obesity and 51 did not. Binary logistic regression analyses were performed to determine whether abdominal obesity was associated with the two lipocalin proteins. Lipocalin-2 was significantly associated with abdominal obesity in the unadjusted model (Odds ratio (OR)=1.014 [95% confidence interval (CI): 1.000, 1.028], P=0.05) and after adjusting for patient related (age, ethnicity, and diabetes mellitus) and pancreatitis related (aetiology, severity, recurrence, and duration of AP) characteristics (OR=1.018 [95% CI: 1.001, 1.036], p=0.04). Further, the association of LCN-2 with waist circumference was significant in individuals with alcohol aetiology of AP (β=1.082 [95% CI: 1.011, 1.158], p=0.02]. The association between RBP-4 and abdominal obesity was not significant in both unadjusted and adjusted models. These findings indicate that circulating levels of LCN-2 in patients after AP may play a role in chronic low grade inflammation associated with abdominal adiposity and that alcohol consumption may further exacerbate adipose tissue dysfunction.

  17. Splanchnic insulin metabolism in obesity. Influence of body fat distribution.

    PubMed Central

    Peiris, A N; Mueller, R A; Smith, G A; Struve, M F; Kissebah, A H

    1986-01-01

    The effects of obesity and body fat distribution on splanchnic insulin metabolism and the relationship to peripheral insulin sensitivity were assessed in 6 nonobese and 16 obese premenopausal women. When compared with the nonobese women, obese women had significantly greater prehepatic production and portal vein levels of insulin both basally and following glucose stimulation. This increase correlated with the degree of adiposity but not with waist-to-hip girth ratio (WHR). WHR, however, correlated inversely with the hepatic extraction fraction and directly with the posthepatic delivery of insulin. The latter correlated with the degree of peripheral insulinemia. The decline in hepatic insulin extraction with increasing WHR also correlated with the accompanying diminution in peripheral insulin sensitivity. Increasing adiposity is thus associated with insulin hypersecretion. The pronounced hyperinsulinemia of upper body fat localization, however, is due to an additional defect in hepatic insulin extraction. This defect is closely allied with the decline in peripheral insulin sensitivity. PMID:3537010

  18. [Metabolic parameters and risk factors associated with abdominal obesity among female adolescents in public schools in the Distrito Federal (Brazil)].

    PubMed

    Pinto, Karina Alves de Castro; Priore, Silvia Eloiza; de Carvalho, Kênia Mara Baiocchi

    2011-03-01

    This study aimed to estimate the prevalence of abdominal obesity and investigate their association with parameters markers of metabolic syndrome (MS) and its risk factors in female adolescents. It is a cross-sectional study with 150 adolescents from 10 public schools in the Federal District, Brazil. The presence of abdominal obesity was considered by measuring waist circumference above the 80th percentile, according to Taylor et al. (2000). The associated factors included sociodemographic characteristics, health status of adolescents and their parents, physical activity, eating habits, blood pressure and biochemical profile. The abdominal obesity prevalence ratio (PR) was estimated by Poisson regression model, with 95% CI. Among the adolescents studied (age= 15.6 +/- 0.8 years; BMI = 21.0 +/- 3.0 kg/m2), prevalence of abdominal obesity was 20%, and this condition was not associated with sociodemographic variables, physical activity and diet. However, abdominal obesity was significantly associated with intake of less than 4 meals a day (PR = 2.27; IC95% 1.27-4.10), previous obesity (PR = 2.36; IC95% 1.31-4.01), history of parental chronic disease (PR = 3.55; IC 95% 1.63-7.75), fasting insulin = 15 uUi/mL (PR = 3.05; IC 95% 1.36-6.82) e HDL-c > 40 mg/dL (PR = 0.39; IC95% 0.23-0.67). In this population, modifiable factors, family history and determinants of MS, such as insulin and HDL-c were associated with abdominal obesity, which points to the need for effective health promotion among adolescents.

  19. Abdominal Adiposity, Not Cardiorespiratory Fitness, Mediates the Exercise-Induced Change in Insulin Sensitivity in Older Adults

    PubMed Central

    Ko, Gifferd; Davidson, Lance E.; Brennan, Andrea M.; Lam, Miu; Ross, Robert

    2016-01-01

    Abdominal obesity and low cardiorespiratory fitness (CRF) are associated with insulin resistance in older adults. Exercise is associated with improvement in insulin sensitivity. Whether this association is mediated by change in CRF and/or abdominal obesity is unclear. The current study is a secondary analysis of data from a randomized controlled trial in Kingston, Ontario. Sedentary older adults (60–80 years) (N = 80) who completed the exercise (N = 59) or control (N = 21) conditions for 6 months were included. CRF was measured using a treadmill test, adipose tissue (AT) by magnetic resonance imaging, and insulin sensitivity by hyperinsulinemic-euglycemic clamp. Waist circumference (WC) was measured at the iliac crest. Mediation analyses were used to assess whether abdominal AT and/or CRF mediated the exercise-induced change in insulin sensitivity. By comparison to controls, reduction (mean ± SD) was observed for visceral (-0.4 ± 0.4 kg) and abdominal subcutaneous (-0.4 ± 0.4) AT depots, WC (-4.1 ± 3.2 cm) and BMI (-0.9 ± 0.8 kg/m2) (p < 0.05). Insulin sensitivity (4.2 ± 5.2 M/I) and CRF (0.2 ± 0.3 L/min) improved in the exercise group (p < 0.05). All AT variables, BMI and WC were mediators of the change in insulin sensitivity (p < 0.05). After adjustment for change in total AT, abdominal AT remained a mediator with an effect ratio of 0.79 (p < 0.05), whereas total AT was not significant when adjusted for abdominal AT (p > 0.05). The effect ratio for change in WC and BMI combined (0.63, p<0.05) was greater than either alone. In conclusion, CRF did not mediate the exercise-induced change in insulin sensitivity in older adults. Abdominal adiposity was a strong mediator independent of change in total adiposity. PMID:27936206

  20. Abdominal obesity: a marker of ectopic fat accumulation.

    PubMed

    Smith, Ulf

    2015-05-01

    In the early 1980s, we analyzed the metabolic profile of 930 men and women and concluded that an abdominal distribution of fat for a given BMI is associated with increased insulin resistance and risk of developing type 2 diabetes and cardiovascular disease. The correlation between abdominal fat and metabolic dysfunction has since been validated in many studies, and waist circumference is now a criterion for the diagnosis of metabolic syndrome. Several mechanisms for this relationship have been postulated; however, we now know that visceral fat is only one of many ectopic fat depots used when the subcutaneous adipose tissue cannot accommodate excess fat because of its limited expandability.

  1. [Influence of smoking and abdominal obesity on lung age].

    PubMed

    Sakamoto, Kyoko; Sonobe, Hiroshi; Hiroi, Ayako; Tanaka, Hiromi; Hino, Yumiko; Takahuta, Keisuke; Ikeda, Taeko; Habara, Toshiyuki

    2011-09-01

    Smoking is the riskiest factor for impairment of pulmonary function. Recent researches have indicated that abdominal obesity is also associated with the impairment. 'Lung age' is a novel index to evaluate respiratory function, and it is calculated from the data of the height, sex, and forced expiratory volume in 1-second. Using 'lung age' as an index, we studied on the relationship of 'lung age' to smoking, waist circumference, BMI, or metabolic syndrome. The study population included 1,681 persons who visited our Medical Checkup Office, and the population consisted of smoker group (n = 279) and non-smoker group (n = 1,402). In both men and women, 'lung age' was significantly higher in the smoker group than in non-smoker group (p < 0.05). In addition, the smoker group and non-smoker group were classified by waist circumference, BMI, and the presence of metabolic syndrome, respectively. As a result, 'lung age' of smoker with abdominal obesity group, smoker with obesity group, and smoker with metabolic syndrome group were significantly high. Furthermore, in multivariate linear regression analysis, we examined relation between 'lung age' and the following factors including gender, smoking, waist circumference, BMI and metabolic syndrome. There was closely related to 'lung age' in order of gender, smoking, metabolic syndrome, and waist circumference. Both smoking and abdominal obesity should be significant risk factors in increasing 'lung age'.

  2. Determinants of High Fasting Insulin and Insulin Resistance Among Overweight/Obese Adolescents

    PubMed Central

    Ling, Jerri Chiu Yun; Mohamed, Mohd Nahar Azmi; Jalaludin, Muhammad Yazid; Rampal, Sanjay; Zaharan, Nur Lisa; Mohamed, Zahurin

    2016-01-01

    Hyperinsulinaemia is the earliest subclinical metabolic abnormality, which precedes insulin resistance in obese children. An investigation was conducted on the potential predictors of fasting insulin and insulin resistance among overweight/obese adolescents in a developing Asian country. A total of 173 overweight/obese (BMI > 85th percentile) multi-ethnic Malaysian adolescents aged 13 were recruited from 23 randomly selected schools in this cross-sectional study. Waist circumference (WC), body fat percentage (BF%), physical fitness score (PFS), fasting glucose and fasting insulin were measured. Insulin resistance was calculated using homeostasis model assessment of insulin resistance (HOMA-IR). Adjusted stepwise multiple regression analysis was performed to predict fasting insulin and HOMA-IR. Covariates included pubertal stage, socioeconomic status, nutritional and physical activity scores. One-third of our adolescents were insulin resistant, with girls having significantly higher fasting insulin and HOMA-IR than boys. Gender, pubertal stage, BMI, WC and BF% had significant, positive moderate correlations with fasting insulin and HOMA-IR while PFS was inversely correlated (p < 0.05). Fasting insulin was primarily predicted by gender-girls (Beta = 0.305, p < 0.0001), higher BMI (Beta = −0.254, p = 0.02) and greater WC (Beta = 0.242, p = 0.03). This study demonstrated that gender, BMI and WC are simple predictors of fasting insulin and insulin resistance in overweight/obese adolescents. PMID:27824069

  3. Physical inactivity and obesity underlie the insulin resistance of aging.

    PubMed

    Amati, Francesca; Dubé, John J; Coen, Paul M; Stefanovic-Racic, Maja; Toledo, Frederico G S; Goodpaster, Bret H

    2009-08-01

    OBJECTIVE Age-associated insulin resistance may underlie the higher prevalence of type 2 diabetes in older adults. We examined a corollary hypothesis that obesity and level of chronic physical inactivity are the true causes for this ostensible effect of aging on insulin resistance. RESEARCH DESIGN AND METHODS We compared insulin sensitivity in 7 younger endurance-trained athletes, 12 older athletes, 11 younger normal-weight subjects, 10 older normal-weight subjects, 15 younger obese subjects, and 15 older obese subjects using a glucose clamp. The nonathletes were sedentary. RESULTS Insulin sensitivity was not different in younger endurance-trained athletes versus older athletes, in younger normal-weight subjects versus older normal-weight subjects, or in younger obese subjects versus older obese subjects. Regardless of age, athletes were more insulin sensitive than normal-weight sedentary subjects, who in turn were more insulin sensitive than obese subjects. CONCLUSIONS Insulin resistance may not be characteristic of aging but rather associated with obesity and physical inactivity.

  4. Obesity is associated with increased seminal insulin and leptin alongside reduced fertility parameters in a controlled male cohort

    PubMed Central

    2014-01-01

    Background Obesity appears to be associated with male reproductive dysfunction and infertility, although this has been inconsistent and inconclusive. Insulin and leptin are known mediators and modulators of the hypothalamus-pituitary-testes axis, contributing to the regulation of male reproductive potential and overall wellbeing. These hormones are also present in semen influencing sperm functions. Although abdominal obesity is closely associated with insulin resistance (hyperinsulinaemia), hyperleptinaemia and glucose dysfunction, changes in seminal plasma concentrations of insulin, leptin and glucose in obese males has not previously been investigated. Methods This small case controlled study assessed serum and seminal concentrations of insulin, leptin and glucose in obese (BMI > =30; n = 23) and non-obese (BMI < 30; n = 19) males. Following a detailed medical history and examination, participants meeting the inclusion criteria were entered for data analysis. Body parameters such as BMI, waist and hip circumference and the waist hip ratio were measured. Serum and semen samples were collected and assayed for insulin, leptin and glucose. Semen samples also underwent a standard semen analysis, with sperm mitochondrial membrane potential (MMP) and DNA fragmentation (DF). Results Obesity was associated with increased serum and seminal insulin and leptin, with no significant difference in seminal glucose. Serum and seminal concentrations of insulin and leptin were positively correlated. Furthermore, obesity was associated with decreased sperm concentration, sperm vitality and increased MMP and DF, with a non-significant impact on motility and morphology. Conclusions Hyperinsulinaemia and hyperleptinaemia are associated with increased seminal insulin and leptin concentrations, which may negatively impact male reproductive function in obesity. Insulin was also found to be highly concentrated in the seminal plasma of both groups. This data will contribute

  5. Obesity, insulin resistance, NASH and hepatocellular carcinoma.

    PubMed

    Yu, Jun; Shen, Jiayun; Sun, Ting Ting; Zhang, Xiang; Wong, Nathalie

    2013-12-01

    Epidemiological and clinical data have clearly demonstrated that non-alcoholic steatohepatitis (NASH) predisposes risk to the development of hepatocellular carcinoma (HCC). NASH is the liver manifestation of metabolic syndrome, which constellates obesity, insulin resistance and dyslipidemia. Although the percentage of patients diagnosed annually with NASH-associated HCC is still relatively low, this number signifies a large population due to the rapidly increasing incidence of obesity and diabetes globally. Fundamental studies on lipid storage, regulation of adipose factors, inflammatory cytokine recruitments and oxidative stress have provided insights into NASH as well as metabolic syndrome. Recent evidence also indicates the significant role of genetic factors in contributing to the pathogenesis of NASH and induced hepatic malignancy. In this review, we attempt to collate current research on NASH biology that lead to our understandings on how metabolic disorders may intersect with cancer development. We also discuss study models that have supported discoveries of molecular and cellular defects, and offered a perspective on therapeutic developments. These studies have collectively increased our knowledge on the complex signaling pathways involved in NASH and cancer, and provided the foundation for improved clinical management of patients with metabolic diseases.

  6. Dysregulation of the peripheral and adipose tissue endocannabinoid system in human abdominal obesity.

    PubMed

    Blüher, Matthias; Engeli, Stefan; Klöting, Nora; Berndt, Janin; Fasshauer, Mathias; Bátkai, Sándor; Pacher, Pál; Schön, Michael R; Jordan, Jens; Stumvoll, Michael

    2006-11-01

    The endocannabinoid system has been suspected to contribute to the association of visceral fat accumulation with metabolic diseases. We determined whether circulating endocannabinoids are related to visceral adipose tissue mass in lean, subcutaneous obese, and visceral obese subjects (10 men and 10 women in each group). We further measured expression of the cannabinoid type 1 (CB(1)) receptor and fatty acid amide hydrolase (FAAH) genes in paired samples of subcutaneous and visceral adipose tissue in all 60 subjects. Circulating 2-arachidonoyl glycerol (2-AG) was significantly correlated with body fat (r = 0.45, P = 0.03), visceral fat mass (r = 0.44, P = 0.003), and fasting plasma insulin concentrations (r = 0.41, P = 0.001) but negatively correlated to glucose infusion rate during clamp (r = 0.39, P = 0.009). In visceral adipose tissue, CB(1) mRNA expression was negatively correlated with visceral fat mass (r = 0.32, P = 0.01), fasting insulin (r = 0.48, P < 0.001), and circulating 2-AG (r = 0.5, P < 0.001), whereas FAAH gene expression was negatively correlated with visceral fat mass (r = 0.39, P = 0.01) and circulating 2-AG (r = 0.77, P < 0.001). Our findings suggest that abdominal fat accumulation is a critical correlate of the dysregulation of the peripheral endocannabinoid system in human obesity. Thus, the endocannabinoid system may represent a primary target for the treatment of abdominal obesity and associated metabolic changes.

  7. Prevalence of Overweight, Obesity, and Abdominal Obesity in a Representative Sample of Portuguese Adults

    PubMed Central

    Sardinha, Luís B.; Santos, Diana A.; Silva, Analiza M.; Coelho-e-Silva, Manuel J.; Raimundo, Armando M.; Moreira, Helena; Santos, Rute; Vale, Susana; Baptista, Fátima; Mota, Jorge

    2012-01-01

    This study determined the prevalence of overweight, obesity, and abdominal obesity in the Portuguese adults and examined the relationship between above mentioned prevalences and educational level. Body mass, stature, and waist circumference were measured in a representative sample of the Portuguese population aged 18–103 years (n = 9,447; 18–64 years: n = 6,908; ≥65 years: n = 2,539). Overweight and obesity corresponded to a body mass index ranging between 25–29.9 kg/m2 and ≥30 kg/m2, respectively. Abdominal obesity was assessed as >102 cm for males and >88 cm for females. After adjusting for educational level, the combined prevalences of overweight and obesity were 66.6% in males and 57.9% in females (18–64 years). Respective values in older adults (≥65 years) were 70.4% for males and 74.7% for females. About 19.3% of adult males and 37.9% of adult females presented abdominal obesity. Correspondent values in older adults were 32.1%, for males, and 69.7%, for females. In adults, low educational level was related to an increased risk for overweight (OR = 2.54; 95% CI: 2.08–3.09), obesity (OR = 2.76; 95% CI: 2.20–3.45), and abdominal obesity (OR = 5.48; 95% CI: 4.60–6.52). This reinforces the importance of adjusting public health strategies for educational level. PMID:23118905

  8. Grizzly bears exhibit augmented insulin sensitivity while obese prior to a reversible insulin resistance during hibernation.

    PubMed

    Nelson, O Lynne; Jansen, Heiko T; Galbreath, Elizabeth; Morgenstern, Kurt; Gehring, Jamie Lauren; Rigano, Kimberly Scott; Lee, Jae; Gong, Jianhua; Shaywitz, Adam J; Vella, Chantal A; Robbins, Charles T; Corbit, Kevin C

    2014-08-05

    The confluence of obesity and diabetes as a worldwide epidemic necessitates the discovery of new therapies. Success in this endeavor requires translatable preclinical studies, which traditionally employ rodent models. As an alternative approach, we explored hibernation where obesity is a natural adaptation to survive months of fasting. Here we report that grizzly bears exhibit seasonal tripartite insulin responsiveness such that obese animals augment insulin sensitivity but only weeks later enter hibernation-specific insulin resistance (IR) and subsequently reinitiate responsiveness upon awakening. Preparation for hibernation is characterized by adiposity coupled to increased insulin sensitivity via modified PTEN/AKT signaling specifically in adipose tissue, suggesting a state of "healthy" obesity analogous to humans with PTEN haploinsufficiency. Collectively, we show that bears reversibly cope with homeostatic perturbations considered detrimental to humans and describe a mechanism whereby IR functions not as a late-stage metabolic adaptation to obesity, but rather a gatekeeper of the fed-fasting transition.

  9. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance.

    PubMed Central

    Steinberg, H O; Chaker, H; Leaming, R; Johnson, A; Brechtel, G; Baron, A D

    1996-01-01

    To test the hypothesis that obesity/insulin resistance impairs both endothelium-dependent vasodilation and insulin-mediated augmentation of endothelium-dependent vasodilation, we studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of methacholine chloride (MCh) or sodium nitroprusside (SNP) during saline infusion and euglycemic hyperinsulinemia in lean insulin-sensitive controls (C), in obese insulin-resistant subjects (OB), and in subjects with non-insulin-dependent diabetes mellitus (NIDDM). MCh induced increments in LBF were approximately 40% and 55% lower in OB and NIDDM, respectively, as compared with C (P < 0.05). Euglycemic hyperinsulinemia augmented the LBF response to MCh by - 50% in C (P < 0.05 vs saline) but not in OB and NIDDM. SNP caused comparable increments in LBF in all groups. Regression analysis revealed a significant inverse correlation between the maximal LBF change in response to MCh and body fat content. Thus, obesity/insulin resistance is associated with (a) blunted endothelium-dependent, but normal endothelium-independent vasodilation and (b) failure of euglycemic hyperinsulinemia to augment endothelium-dependent vasodilation. Therefore, obese/insulin-resistant subjects are characterized by endothelial dysfunction and endothelial resistance to insulin's effect on enhancement of endothelium-dependent vasodilation. This endothelial dysfunction could contribute to the increased risk of atherosclerosis in obese insulin-resistant subjects. PMID:8647954

  10. Insulin and Leptin Relations in Obesity: A Multimedia Approach

    ERIC Educational Resources Information Center

    Yokaichiya, Daniela K.; Galembeck, Eduardo; Torres, Bayardo B.; Da Silva, Jose Antonio; de Araujo, Daniele R.

    2008-01-01

    Obesity has been recognized as a worldwide public health problem. It significantly increases the chances of developing several diseases, including Type II diabetes. The roles of insulin and leptin in obesity involve reactions that can be better understood when they are presented step by step. The aim of this work was to design software with data…

  11. Harmonizing the diagnosis of metabolic syndrome--focusing on abdominal obesity.

    PubMed

    Silva, Valter; Stanton, Kenneth R; Grande, Antonio José

    2013-04-01

    In 2009, important health organizations met to construct a Joint Scientific Statement (JSS) intended to harmonize the diagnosis of metabolic syndrome worldwide. The JSS aimed to unify the diagnostic criteria of metabolic syndrome, particularly in relation to whether to include abdominal obesity as a criterion of diagnosis. A large part of the JSS is devoted to discussing the diagnosis of abdominal obesity. More specifically, 9 of the 16 papers focused on abdominal obesity. Continuing this emphasis, we discuss the harmonization of the diagnosis of metabolic syndrome worldwide, specifically focusing on the need to improve the diagnosis of abdominal obesity.

  12. [MORPHOLOGICAL PECULIARITIES OF MUSCULO-APONEUROTIC TISSUES OF ANTERIOR ABDOMINAL WALL IN PATIENTS, SUFFERING MORBID OBESITY].

    PubMed

    Usenko, O Yu; Gomolyako, I V; Kondratenko, B M; Moskalenko, V V

    2015-11-01

    Results of morphological investigation of musculo-aponeurotic structures of anterior abdominal wall were presented in the morbid obesity patients. The role of obesity as a primary cause for morphofunctional insufficience of musculo-aponeurotic structures was established.

  13. Homocysteine levels in morbidly obese patients: its association with waist circumference and insulin resistance.

    PubMed

    Vayá, Amparo; Rivera, Leonor; Hernández-Mijares, Antonio; de la Fuente, Miguel; Solá, Eva; Romagnoli, Marco; Alis, R; Laiz, Begoña

    2012-01-01

    The association between morbid obesity and hyperhomocysteinemia (HH) remains controversial and the nature of this relationship needs to be clarified as several metabolic, lipidic, inflammatory and anthropometric alterations that accompany morbid obesity may be involved. In 66 morbidly obese patients, 47 women and 19 men aged 41 ± 12 years and 66 normo-weight subjects, 43 women and 23 men, aged 45 ± 11 years, we determined homocysteine (Hcy) levels along with lipidic, anthropometric, inflammatory and insulin resistance markers. In addition, we investigated the effect of Metabolic Syndrome (MS) and its components on Hcy levels. Obese patients had statistically higher Hcy levels than controls: 12.76 ± 5.30 μM vs. 10.67 ± 2.50 μM; p = 0.006. Moreover, morbidly obese subjects showed higher waist circumference, glucose, insulin, HOMA, leptin, triglycerides, fibrinogen, C reactive protein (CRP) (p < 0.001, respectively), and lower vitamin B12 (p = 0.002), folic acid and HDL-cholesterol (p < 0.001, respectively). In the multivariate regression analysis, waist circumference, glucose, leptin and folic acid levels were independent predictors for Hcy values (p < 0.050). When obese patients were classified as having MS or not, no differences in Hcy levels were found between the two groups (p = 0.752). Yet when we analysed separately each MS component, only abdominal obesity was associated with Hcy levels (p = 0.031). Moreover when considering glucose >110 mg/dL (NCEP-ATPIII criteria) instead of glucose intolerance >100 mg/dl (updated ATPIII criteria), it also was associated with HH (p = 0.042). These results were confirmed in the logistic regression analysis where abdominal obesity and glucose >115 mg/dL constitute independent predictors for HH (OR = 3.2; CI: 1.23-13.2; p = 0.032, OR: 4.6; CI: 1.7-22.2; p = 0.016, respectively). The results of our study indicate that increased Hcy levels are related mostly with abdominal obesity and with insulin resistance. Thus, HH may

  14. Obesity, insulin resistance and comorbidities – Mechanisms of association

    PubMed Central

    Castro, Ana Valeria B.; Kolka, Cathryn M.; Kim, Stella P.; Bergman, Richard N.

    2015-01-01

    Overall excess of fat, usually defined by the body mass index, is associated with metabolic (e.g. glucose intolerance, type 2 diabetes mellitus (T2DM), dyslipidemia) and non-metabolic disorders (e.g. neoplasias, polycystic ovary syndrome, non-alcoholic fat liver disease, glomerulopathy, bone fragility etc.). However, more than its total amount, the distribution of adipose tissue throughout the body is a better predictor of the risk to the development of those disorders. Fat accumulation in the abdominal area and in non-adipose tissue (ectopic fat), for example, is associated with increased risk to develop metabolic and non-metabolic derangements. On the other hand, observations suggest that individuals who present peripheral adiposity, characterized by large hip and thigh circumferences, have better glucose tolerance, reduced incidence of T2DM and of metabolic syndrome. Insulin resistance (IR) is one of the main culprits in the association between obesity, particularly visceral, and metabolic as well as non-metabolic diseases. In this review we will highlight the current pathophysiological and molecular mechanisms possibly involved in the link between increased VAT, ectopic fat, IR and comorbidities. We will also provide some insights in the identification of these abnormalities. PMID:25211442

  15. Hypertriglyceridemia is a practical biomarker of metabolic syndrome in individuals with abdominal obesity.

    PubMed

    Li, Zhaoping; Deng, Max L; Tseng, Chi-Hong; Heber, David

    2013-04-01

    Individuals with the metabolic syndrome have a significantly higher risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease. Body mass index (BMI) and waist circumference are inaccurate methods for assessing abdominal obesity; in addition, some obese individuals are metabolically healthy while some normal weight individuals have metabolic syndrome. The methods used to visualize intra-abdominal fat, such as computed tomography (CT) scan and magnetic resonance imaging (MRI), are not available to primary care practitioners as screening methods for the primary care patient. The present study examined commonly used biomarkers to assess which of them would be most predictive of metabolic syndrome to assess the feasibility of using indicators other than BMI in the assessment of obesity-associated disease risk in the primary care setting. We examined 169 (118 females, 51 males) obese individuals with increased waist circumference (>102 cm for men and >85 cm for women), who were patients at the UCLA Risk Factor Obesity Clinic. Of these, 59 had three or more criteria associated with metabolic syndrome. In a multivariate linear regression model including body weight, BMI, waist circumference, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, glucose, high-density lipoprotein, and triglycerides (TG), only log TG and glucose values were significantly associated with the presence of metabolic syndrome (p<0.001). Both TG and fasting glucose levels were significantly and positively correlated with fasting insulin (p<0.001), homeostasis model assessment (HOMA) (p<0.001). TG were correlated negatively with adiponectin (p<0.01) and positively with high-sensitivity C-reactive protein. We conclude that the presence of elevated TG is independently associated with metabolic syndrome and is a likely predictor for insulin resistance in individuals with increased waist circumference. This finding has significant implications for screening obese and normal

  16. Role of the endocannabinoid system in abdominal obesity and the implications for cardiovascular risk.

    PubMed

    Rosenson, Robert S

    2009-01-01

    Several cardiometabolic factors present in obese and insulin-resistant individuals represent a continuum of increasing risk for the development of type 2 diabetes and cardiovascular disease. The importance of abdominal obesity as an independent risk factor is underscored by its association with adverse endocrine function. Recent evidence from animal and human studies has shown a role for the endocannabinoid system in maintaining energy balance and glucose and lipoprotein metabolism, with overactivity linked to aberrant glycemic and lipoprotein control, and a link to adiposity. Modulation of this system through endocannabinoid-receptor blockade has resulted in an improvement in a number of important risk factors in clinical trials, including visceral and subcutaneous abdominal adipose tissue, glucose tolerance, dyslipidemia and measures of inflammation. These findings may have significant implications for the management of patients at risk of developing cardiovascular and metabolic disease; however, the occurrence of psychiatric adverse events with rimonabant may preclude further development of centrally active endocannabinoid receptor antagonists for the treatment of cardiometabolic disorders. Future research is needed to explore the role of selective peripheral CB(1) receptor antagonists in the treatment of patients at high cardiometabolic risk.

  17. Fast food, central nervous system insulin resistance, and obesity.

    PubMed

    Isganaitis, Elvira; Lustig, Robert H

    2005-12-01

    Rates of obesity and insulin resistance have climbed sharply over the past 30 years. These epidemics are temporally related to a dramatic rise in consumption of fast food; until recently, it was not known whether the fast food was driving the obesity, or vice versa. We review the unique properties of fast food that make it the ideal obesigenic foodstuff, and elucidate the mechanisms by which fast food intake contributes to obesity, emphasizing its effects on energy metabolism and on the central regulation of appetite. After examining the epidemiology of fast food consumption, obesity, and insulin resistance, we review insulin's role in the central nervous system's (CNS) regulation of energy balance, and demonstrate the role of CNS insulin resistance as a cause of leptin resistance and in the promotion of the pleasurable or "hedonic" responses to food. Finally, we analyze the characteristics of fast food, including high-energy density, high fat, high fructose, low fiber, and low dairy intake, which favor the development of CNS insulin resistance and obesity.

  18. Abdominal Myosteatosis is Independently Associated to Hyperinsulinemia and Insulin Resistance among Older Men without Diabetes

    PubMed Central

    Miljkovic, Iva; Cauley, Jane A.; Wang, Patty Y.; Holton, Kathleen F.; Lee, Christine G.; Sheu, Yahtyng; Barrett-Connor, Elizabeth; Hoffman, Andrew R.; Lewis, Cora B.; Orwoll, Eric S.; Stefanick, Marcia L.; Strotmeyer, Elsa S.; Marshall, Lynn M.

    2013-01-01

    Design and Methods Skeletal muscle adipose tissue (AT) infiltration (myosteatosis) increases with aging and may contribute to the development of type 2 diabetes mellitus (T2DM). It remains unclear if myosteatosis is associated to glucose and insulin homeostasis independent of total and central adiposity. We evaluated the association between intermuscular AT (IMAT) in the abdominal skeletal muscles (total, paraspinal and psoas) and fasting serum glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) in 393 non-diabetic Caucasian men aged 65+. Abdominal IMAT, visceral (VAT) and subcutaneous (SAT) AT (cm3) were measured by quantitative computed tomography at the L4-L5 intervertebral space. Results In age, study site, height and muscle volume adjusted regression analyses, total abdominal and psoas (but not paraspinal) IMAT were positively associated with glucose, insulin and HOMA-IR (all P < 0.003). The associations between total abdominal and psoas IMAT and insulin and HOMA-IR remained significant after further adjusting for lifestyle factors, as well as DXA total body fat, VAT or SAT in separate models (all P <0.009). Conclusions Our study indicates a previously unreported, independent association between abdominal myosteatosis and hyperinsulinemia and insulin resistance among older Caucasian men. These associations may be specific for particular abdominal muscle depots, illustrating the potential importance of separately studying specific muscle groups. PMID:23408772

  19. Obesity, insulin resistance and breast cancer outcomes.

    PubMed

    Goodwin, Pamela J

    2015-11-01

    There is growing evidence that obesity is associated with poor outcomes in early stage breast cancer. This paper addresses four current areas of focus: 1. Is obesity associated with poor outcomes in all biologic subtypes of breast cancer? 2. Does obesity effect AI efficacy or estrogen suppression in the adjuvant setting? 3. What are the potential biologic underpinnings of the obesity-breast cancer association? 4. Are intervention studies warranted? If so, which interventions in which populations? Research is needed to resolve these questions; intervention trials involving lifestyle interventions or targeting the biology postulated to link obesity and cancer are recommended.

  20. Monomeric Tartrate Resistant Acid Phosphatase Induces Insulin Sensitive Obesity

    PubMed Central

    Lång, Pernilla; van Harmelen, Vanessa; Rydén, Mikael; Kaaman, Maria; Parini, Paolo; Carneheim, Claes; Cassady, A. Ian; Hume, David A.; Andersson, Göran; Arner, Peter

    2008-01-01

    Background Obesity is associated with macrophage infiltration of adipose tissue, which may link adipose inflammation to insulin resistance. However, the impact of inflammatory cells in the pathophysiology of obesity remains unclear. Tartrate resistant acid phosphatase (TRAP) is an enzyme expressed by subsets of macrophages and osteoclasts that exists either as an enzymatically inactive monomer or as an active, proteolytically processed dimer. Principal Findings Using mice over expressing TRAP, we show that over-expression of monomeric, but not the dimeric form in adipose tissue leads to early onset spontaneous hyperplastic obesity i.e. many small fat cells. In vitro, recombinant monomeric, but not proteolytically processed TRAP induced proliferation and differentiation of mouse and human adipocyte precursor cells. In humans, monomeric TRAP was highly expressed in the adipose tissue of obese individuals. In both the mouse model and in the obese humans the source of TRAP in adipose tissue was macrophages. In addition, the obese TRAP over expressing mice exhibited signs of a low-grade inflammatory reaction in adipose tissue without evidence of abnormal adipocyte lipolysis, lipogenesis or insulin sensitivity. Conclusion Monomeric TRAP, most likely secreted from adipose tissue macrophages, induces hyperplastic obesity with normal adipocyte lipid metabolism and insulin sensitivity. PMID:18320034

  1. Whole-Body and Hepatic Insulin Resistance in Obese Children

    PubMed Central

    Ibarra-Reynoso, Lorena del Rocío; Pisarchyk, Liudmila; Pérez-Luque, Elva Leticia; Garay-Sevilla, Ma. Eugenia; Malacara, Juan Manuel

    2014-01-01

    Background Insulin resistance may be assessed as whole body or hepatic. Objective To study factors associated with both types of insulin resistance. Methods Cross-sectional study of 182 obese children. Somatometric measurements were registered, and the following three adiposity indexes were compared: BMI, waist-to-height ratio and visceral adiposity. Whole-body insulin resistance was evaluated using HOMA-IR, with 2.5 as the cut-off point. Hepatic insulin resistance was considered for IGFBP-1 level quartiles 1 to 3 (<6.67 ng/ml). We determined metabolite and hormone levels and performed a liver ultrasound. Results The majority, 73.1%, of obese children had whole-body insulin resistance and hepatic insulin resistance, while 7% did not have either type. HOMA-IR was negatively associated with IGFBP-1 and positively associated with BMI, triglycerides, leptin and mother's BMI. Girls had increased HOMA-IR. IGFBP-1 was negatively associated with waist-to-height ratio, age, leptin, HOMA-IR and IGF-I. We did not find HOMA-IR or IGFBP-1 associated with fatty liver. Conclusion In school-aged children, BMI is the best metric to predict whole-body insulin resistance, and waist-to-height ratio is the best predictor of hepatic insulin resistance, indicating that central obesity is important for hepatic insulin resistance. The reciprocal negative association of IGFBP-1 and HOMA-IR may represent a strong interaction of the physiological processes of both whole-body and hepatic insulin resistance. PMID:25411786

  2. Short term low-calorie diet improves insulin sensitivity and metabolic parameters in obese women.

    PubMed

    Bôas Huguenin, Grazielle Vilas; Kimi Uehara, Sofia; Nogueira Netto, José Firmino; Gaspar de Moura, Egberto; Rosa, Glorimar; da Fonseca Passos, Magna Cottini

    2014-07-01

    Obesity and insulin resistance are associated with an increase of cardiovascular risk factors, including adipocytokines. The aim of this study was to investigate the effect of low-calorie diet on serum lipids, adipokines, insulin resistance and body composition in obese women. It was a clinical trial with class I obese women aged 30-45 years submitted to hypocaloric diet for 90 days. Dietary intake, anthropometric parameters, body composition, serum lipids, glucose, insulin, leptin, adiponectin, HOMA-IR and QUICKI indexes were evaluated at the baseline, 30, 60 and 90 days. There was 30% significant decrease in energy intake, and also decrease in body weight, body mass index and waist circumference (p < 0.01) throughout the treatment period. Despite the amount of lean body mass (kg) reduced in average, it was observed that lean body mass (%) had increased (p < 0.01) and that the amount of fat body mass (kg) had decreased significantly in the third month (p < 0.05). Systolic blood pressure reduced up to -5mmHg (p < 0.05) after 90 days. Was observed a decrease (p < 0.05) on serum insulin and HOMA-IR until the 60th day, while the serum adiponectin increased (p < 0.01) during treatment. Corroborating with the reduction of fat body mass and weight, serum leptin also reduced (p < 0.01). These results suggest that the short-term low-calorie diet reduces total body fat, mainly found in the abdominal region, and efficiently improve insulin sensitivity decreasing cardiovascular risk in obese women.

  3. Vitamin D insufficiency and insulin resistance in obese adolescents

    PubMed Central

    Tosh, Aneesh K.; Belenchia, Anthony M.

    2014-01-01

    Obese adolescents represent a particularly vulnerable group for vitamin D deficiency which appears to have negative consequences on insulin resistance and glucose homeostasis. Poor vitamin D status is also associated with future risk of type 2 diabetes and metabolic syndrome in the obese. The biological mechanisms by which vitamin D influences glycemic control in obesity are not well understood, but are thought to involve enhancement of peripheral/hepatic uptake of glucose, attenuation of inflammation and/or regulation of insulin synthesis/secretion by pancreatic β cells. Related to the latter, recent data suggest that the active form of vitamin, 1,25-dihydroxyvitamin D, does not impact insulin release in healthy pancreatic islets; instead they require an environmental stressor such as inflammation or vitamin D deficiency to see an effect. To date, a number of observational studies exploring the relationship between the vitamin D status of obese adolescents and markers of glucose homeostasis have been published. Most, although not all, show significant associations between circulating 25-hydroxyvitamn D concentrations and insulin sensitivity/resistance indices. In interpreting the collective findings of these reports, significant considerations surface including the effects of pubertal status, vitamin D status, influence of parathyroid hormone status and the presence of nonalcoholic fatty liver disease. The few published clinical trials using vitamin D supplementation to improve insulin resistance and impaired glucose tolerance in obese adolescents have yielded beneficial effects. However, there is a need for more randomized controlled trials. Future investigations should involve larger sample sizes of obese adolescents with documented vitamin D deficiency, and careful selection of the dose, dosing regimen and achievement of target 25-hydroxyvitamn D serum concentrations. These trials should also include clamp-derived measures of in vivo sensitivity and

  4. Serum 25(OH)D and adipokines levels in people with abdominal obesity.

    PubMed

    Karonova, T; Belyaeva, O; Jude, E B; Tsiberkin, A; Andreeva, A; Grineva, E; Pludowski, P

    2016-09-11

    Abdominal obesity is a risk factor for cardiovascular disease and diabetes mellitus and has been associated with vitamin D deficiency. Some studies have suggested an association between obesity and adipokine levels as well as low serum 25-hydroxyvitamin D (25(OH)D) level but the underlying mechanisms of the interlink between vitamin D status and serum leptin and adiponectin concentrations are still disputed. We included 435 residents (132 males) from St. Petersburg, Russia into this study. All subjects had physical examination and demographics noted. Blood was collected after an overnight fast and plasma glucose, insulin, serum lipids, 25(OH)D and adipokines (adiponectin and leptin) concentrations were determined at baseline in all participants. Abdominal obesity was diagnosed in 310 (71.3%) subjects (251 females and 59 males). Vitamin D insufficiency and deficiency were found in 314 (72.2%) subjects. Mean (95% CI) age, body mass index (BMI) and serum 25(OH)D for the cohort were 47.6±11.3years; 28.7±0.2kg/m(2) and 62.5±24.3nmol/l respectively. Serum 25(OH)D level inversely correlated with body weight, waist circumference (WC) and BMI in females but not in males, was lower in diabetic than non-diabetic subjects, and was not significantly different in subjects with and without MetS. WC was positively correlated with leptin and negatively correlated with adiponectin. We found correlation between leptin and serum 25(OH)D level (r=-0.15, p=0.01) but this finding was a characteristic seen only in women. Our study showed a high prevalence of abdominal obesity, vitamin D deficiency and insufficiency in residents from North-West region of Russia, close association between adipokine (leptin, adiponectin) concentrations as well as vitamin D status and body composition (WC, BMI). However in our study the interlink between leptin level and 25(OH)D was found only in females. Further investigations are required to study the relationship between serum 25(OH)D level, obesity and

  5. Bromocriptine and insulin sensitivity in lean and obese subjects

    PubMed Central

    Verberne, H J; Brakema, E; Tepaske, R; Booij, J; Hoekstra, J B; Holleman, F

    2016-01-01

    Bromocriptine is a glucose-lowering drug, which was shown to be effective in obese subjects with insulin resistance. It is usually administered in the morning. The exact working mechanism of bromocriptine still has to be elucidated. Therefore, in this open-label randomized prospective cross-over mechanistic study, we assessed whether the timing of bromocriptine administration (morning vs evening) results in different effects and whether these effects differ between lean and obese subjects. We studied the effect of bromocriptine on insulin sensitivity in 8 lean and 8 overweight subjects using an oral glucose tolerance test. The subjects used bromocriptine in randomized cross-over order for 2 weeks in the morning and 2 weeks in the evening. We found that in lean subjects, bromocriptine administration in the evening resulted in a significantly higher post-prandial insulin sensitivity as compared with the pre-exposure visit (glucose area under the curve (AUC) 742 mmol/L * 120 min (695–818) vs 641 (504–750), P = 0.036, AUC for insulin did not change, P = 0.575). In obese subjects, both morning and evening administration of bromocriptine resulted in a significantly higher insulin sensitivity: morning administration in obese: insulin AUC (55,900 mmol/L * 120 min (43,236–96,831) vs 36,448 (25,213–57,711), P = 0.012) and glucose AUC P = 0.069; evening administration in obese: glucose AUC (735 mmol/L * 120 min (614–988) vs 644 (568–829), P = 0.017) and insulin AUC, P = 0.208. In conclusion, bromocriptine increases insulin sensitivity in both lean and obese subjects. In lean subjects, this effect only occurred when bromocriptine was administrated in the evening, whereas in the obese, insulin sensitivity increased independent of the timing of bromocriptine administration. PMID:27758845

  6. Obesity and the Risk for Surgical Site Infection in Abdominal Surgery.

    PubMed

    Winfield, Robert D; Reese, Stacey; Bochicchio, Kelly; Mazuski, John E; Bochicchio, Grant V

    2016-04-01

    Obesity is a risk factor for surgical site infection (SSI) after abdominal procedures; however, data characterizing the risk of SSI in obese patients during abdominal procedures are lacking. We hypothesized that obesity is an independent risk factor for SSI across wound classes. We analyzed American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) data for 2011. We calculated body mass index (BMI), classifying patients according to National Institute of Health (NIH) BMI groups. We excluded records in which height/weight was not recorded and patients with BMI less than 18.5. We examined patients undergoing open abdominal procedures, performing univariate and multivariate analyses to assess the relative contribution of obesity to SSI. Study criteria were met by 89,148 patients. Obese and morbidly obese patients had significantly greater SSI rates in clean and clean-contaminated cases but not contaminated or dirty/infected cases. Logistic regression confirmed obesity and morbid obesity as being independently associated with the overall SSI development, specifically in clean [Obesity odds ratio (OR) = 1.757, morbid obesity OR = 2.544, P < 0.001] and clean-contaminated (obesity OR = 1.239, morbid obesity OR = 1.287, P < 0.001) cases. Obesity is associated with increased risk of SSI overall, specifically in clean and clean-contaminated abdominal procedures; this is independent of diabetes mellitus. Novel techniques are needed to reduce SSI in this high-risk patient population.

  7. REGULATION OF OBESITY AND INSULIN RESISTANCE BY NITRIC OXIDE

    PubMed Central

    Sansbury, Brian E.; Hill, Bradford G.

    2014-01-01

    Obesity is a risk factor for developing type 2 diabetes and cardiovascular disease and has quickly become a world-wide pandemic with few tangible and safe treatment options. While it is generally accepted that the primary cause of obesity is energy imbalance, i.e., the calories consumed are greater than are utilized, understanding how caloric balance is regulated has proven a challenge. Many “distal” causes of obesity, such as the structural environment, occupation, and social influences, are exceedingly difficult to change or manipulate. Hence, molecular processes and pathways more proximal to the origins of obesity—those that directly regulate energy metabolism or caloric intake—appear to be more feasible targets for therapy. In particular, nitric oxide (NO) is emerging as a central regulator of energy metabolism and body composition. NO bioavailability is decreased in animal models of diet-induced obesity and in obese and insulin resistant patients, and increasing NO output has remarkable effects on obesity and insulin resistance. This review discusses the role of NO in regulating adiposity and insulin sensitivity and places its modes of action into context with the known causes and consequences of metabolic disease. PMID:24878261

  8. Educational inequality in the occurrence of abdominal obesity: Pró-Saúde Study

    PubMed Central

    Alves, Ronaldo Fernandes Santos; Faerstein, Eduardo

    2015-01-01

    OBJECTIVE To estimate the degree of educational inequality in the occurrence of abdominal obesity in a population of non-faculty civil servants at university campi. METHODS In this cross-sectional study, we used data from 3,117 subjects of both genders aged 24 to 65-years old, regarding the baseline of Pró-Saúde Study, 1999-2001. Abdominal obesity was defined according to abdominal circumference thresholds of 88 cm for women and 102 cm for men. A multi-dimensional, self-administered questionnaire was used to evaluate education levels and demographic variables. Slope and relative indices of inequality, and Chi-squared test for linear trend were used in the data analysis. All analyses were stratified by genders, and the indices of inequality were standardized by age. RESULTS Abdominal obesity was the most prevalent among women (43.5%; 95%CI 41.2;45.9), as compared to men (24.3%; 95%CI 22.1;26.7), in all educational strata and age ranges. The association between education levels and abdominal obesity was an inverse one among women (p < 0.001); it was not statistically significant among men (p = 0.436). The educational inequality regarding abdominal obesity in the female population, in absolute terms (slope index of inequality), was 24.0% (95%CI 15.5;32.6). In relative terms (relative index of inequality), it was 2.8 (95%CI 1.9;4.1), after the age adjustment. CONCLUSIONS Gender inequality in the prevalence of abdominal obesity increases with older age and lower education. The slope and relative indices of inequality summarize the strictly monotonous trend between education levels and abdominal obesity, and it described educational inequality regarding abdominal obesity among women. Such indices provide relevant quantitative estimates for monitoring abdominal obesity and dealing with health inequalities. PMID:26465669

  9. Differential hepatic distribution of insulin receptor substrates causes selective insulin resistance in diabetes and obesity

    PubMed Central

    Kubota, Naoto; Kubota, Tetsuya; Kajiwara, Eiji; Iwamura, Tomokatsu; Kumagai, Hiroki; Watanabe, Taku; Inoue, Mariko; Takamoto, Iseki; Sasako, Takayoshi; Kumagai, Katsuyoshi; Kohjima, Motoyuki; Nakamuta, Makoto; Moroi, Masao; Sugi, Kaoru; Noda, Tetsuo; Terauchi, Yasuo; Ueki, Kohjiro; Kadowaki, Takashi

    2016-01-01

    Hepatic insulin signalling involves insulin receptor substrates (Irs) 1/2, and is normally associated with the inhibition of gluconeogenesis and activation of lipogenesis. In diabetes and obesity, insulin no longer suppresses hepatic gluconeogenesis, while continuing to activate lipogenesis, a state referred to as ‘selective insulin resistance'. Here, we show that ‘selective insulin resistance' is caused by the differential expression of Irs1 and Irs2 in different zones of the liver. We demonstrate that hepatic Irs2-knockout mice develop ‘selective insulin resistance', whereas mice lacking in Irs1, or both Irs1 and Irs2, develop ‘total insulin resistance'. In obese diabetic mice, Irs1/2-mediated insulin signalling is impaired in the periportal zone, which is the primary site of gluconeogenesis, but enhanced in the perivenous zone, which is the primary site of lipogenesis. While hyperinsulinaemia reduces Irs2 expression in both the periportal and perivenous zones, Irs1 expression, which is predominantly in the perivenous zone, remains mostly unaffected. These data suggest that ‘selective insulin resistance' is induced by the differential distribution, and alterations of hepatic Irs1 and Irs2 expression. PMID:27708333

  10. Influence of magnesium on insulin resistance in obese women.

    PubMed

    Cruz, Kyria Jayanne Clímaco; de Oliveira, Ana Raquel Soares; Pinto, Denise Pereira; Morais, Jennifer Beatriz Silva; Lima, Fabiana da Silva; Colli, Célia; Torres-Leal, Francisco Leonardo; Marreiro, Dilina do Nascimento

    2014-09-01

    The present study evaluated the influence of magnesium on insulin resistance in obese women. A case-control study involving 114 women on the age between 20 and 50 years old, divided into two groups: control (eutrophic women, n = 59) and case (obese women, n = 55). The analysis of magnesium intake was carried out through the 3-day food record and also NutWin software version 1.5. The plasma, erythrocyte, and urinary magnesium concentrations were determined by flame atomic absorption spectrophotometry. The determinations of serum glucose and serum insulin were performed by enzymatic colorimetric method and chemiluminescence, respectively. The insulin resistance was assessed by homeostasis model assessment insulin resistance (HOMA-IR). The mean values of magnesium intake were lower than those recommended, without difference between groups (p > 0.05). All the patients who were evaluated showed adequate mean concentrations of magnesium in the plasma and erythrocyte. The urinary excretion of this mineral was lower than the reference values in both groups and did not show significant difference (p > 0.05). The values of serum glucose, serum insulin, and HOMA-IR were higher in obese women compared to the control group. A negative correlation was observed between erythrocyte magnesium and glycemic parameters (p < 0.05). Obese patients take in foods with low dietary magnesium content, and they show hypomagnesuria as a compensatory mechanism to keep the plasma concentration of this mineral in adequate levels. The correlation between the erythrocyte magnesium concentration and the parameters of glycemic control suggests the influence of this mineral on the index of insulin resistance in obese women.

  11. Exercise rescues obese mothers’ insulin sensitivity, placental hypoxia and male offspring insulin sensitivity

    PubMed Central

    Fernandez-Twinn, Denise S.; Gascoin, Geraldine; Musial, Barbara; Carr, Sarah; Duque-Guimaraes, Daniella; Blackmore, Heather L.; Alfaradhi, Maria Z.; Loche, Elena; Sferruzzi-Perri, Amanda N.; Fowden, Abigail L.; Ozanne, Susan E.

    2017-01-01

    The prevalence of obesity during pregnancy continues to increase at alarming rates. This is concerning as in addition to immediate impacts on maternal wellbeing, obesity during pregnancy has detrimental effects on the long-term health of the offspring through non-genetic mechanisms. A major knowledge gap limiting our capacity to develop intervention strategies is the lack of understanding of the factors in the obese mother that mediate these epigenetic effects on the offspring. We used a mouse model of maternal-diet induced obesity to define predictive correlations between maternal factors and offspring insulin resistance. Maternal hyperinsulinemia (independent of maternal body weight and composition) strongly associated with offspring insulin resistance. To test causality, we implemented an exercise intervention that improved maternal insulin sensitivity without changing maternal body weight or composition. This maternal intervention prevented excess placental lipid deposition and hypoxia (independent of sex) and insulin resistance in male offspring. We conclude that hyperinsulinemia is a key programming factor and therefore an important interventional target during obese pregnancy, and propose moderate exercise as a promising strategy to improve metabolic outcome in both the obese mother and her offspring. PMID:28291256

  12. Insulin-Dependent Activation of MCH Neurons Impairs Locomotor Activity and Insulin Sensitivity in Obesity.

    PubMed

    Hausen, A Christine; Ruud, Johan; Jiang, Hong; Hess, Simon; Varbanov, Hristo; Kloppenburg, Peter; Brüning, Jens C

    2016-12-06

    Melanin-concentrating-hormone (MCH)-expressing neurons (MCH neurons) in the lateral hypothalamus (LH) are critical regulators of energy and glucose homeostasis. Here, we demonstrate that insulin increases the excitability of these neurons in control mice. In vivo, insulin promotes phosphatidylinositol 3-kinase (PI3K) signaling in MCH neurons, and cell-type-specific deletion of the insulin receptor (IR) abrogates this response. While lean mice lacking the IR in MCH neurons (IR(ΔMCH)) exhibit no detectable metabolic phenotype under normal diet feeding, they present with improved locomotor activity and insulin sensitivity under high-fat-diet-fed, obese conditions. Similarly, obesity promotes PI3 kinase signaling in these neurons, and this response is abrogated in IR(ΔMCH) mice. In turn, acute chemogenetic activation of MCH neurons impairs locomotor activity but not insulin sensitivity. Collectively, our experiments reveal an insulin-dependent activation of MCH neurons in obesity, which contributes via distinct mechanisms to the manifestation of impaired locomotor activity and insulin resistance.

  13. Impact of obesity on recovery and pulmonary functions of obese women undergoing major abdominal gynecological surgeries.

    PubMed

    Moustafa, Ahmed A M; Abdelazim, Ibrahim A

    2016-06-01

    To determine impact of obesity on recovery parameters and pulmonary functions of women undergoing major abdominal gynecological surgeries. Eighty women undergoing major gynecological surgeries were included in this study. Anesthesia was induced by remifentanil bolus, followed by propofol and cisatracurium to facilitate oro-tracheal intubation and was maintained by balanced anesthesia of remifentanil intravenous infusion and sevoflurane in oxygen and air. Time from discontinuation of maintenance anesthesia to fully awake were recorded at 1-min intervals and time from discontinuation of anesthesia until patient was transferred to post-anesthesia care unit (PACU) and discharged from PACU was also recorded. Pulmonary function tests were performed before surgery and repeated 4 h, days 1, 2 and 3 post-operative for evaluation of forced vital capacity, forced expiratory volume in 1 s and peak expiratory flow rate. Occurrence of post-operative complications, re-admission to ICU, hospital stay and morbidities were also recorded. Induction of anesthesia using remifentanil bolus injection resulted in significant decrease of heart rate and arterial pressures compared to pre-operative and pre-induction values. Recovery times were significantly shorter in obese compared to morbidly obese women. Post-operative pulmonary function tests showed significant deterioration compared to pre-operative measures but showed progressive improvement through first 3 post-operative days. Hospital stay was significantly shorter for obese compared to morbid obese women. Obesity delays recovery from general anesthesia, adversely affects pulmonary functions and increases post-operative complications. Remifentanil infusion and sevoflurane could be appropriate combination for obese and morbidly obese women undergoing major surgeries.

  14. Physical Training Improves Insulin Resistance Syndrome Markers in Obese Adolescents.

    ERIC Educational Resources Information Center

    Kang, Hyun-Sik; Gutin, Bernard; Barbeau, Paule; Owens, Scott; Lemmon, Christian R.; Allison, Jerry; Litaker, Mark S.; Le, Ngoc-Anh

    2002-01-01

    Tested the hypothesis that physical training (PT), especially high-intensity PT, would favorably affect components of the insulin resistance syndrome (IRS) in obese adolescents. Data on teens randomized into lifestyle education (LSE) alone, LSE plus moderate -intensity PT, and LSE plus high-intensity PT indicated that PT, especially high-intensity…

  15. Immunity as a link between obesity and insulin resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Type-2 diabetes mellitus (T2DM) is a major health problem in the United States and worldwide. Obesity is causally linked to the pathogenesis of insulin resistance, metabolic syndrome and T2DM. A chronic low-grade inflammation occurring in adipose tissue is at least in part responsible for the obesit...

  16. Does Inflammation Mediate the Association Between Obesity and Insulin Resistance?

    PubMed

    Adabimohazab, Razieh; Garfinkel, Amanda; Milam, Emily C; Frosch, Olivia; Mangone, Alexander; Convit, Antonio

    2016-06-01

    In adult obesity, low-grade systemic inflammation is considered an important step in the pathogenesis of insulin resistance (IR). The association between obesity and inflammation is less well established in adolescents. Here, we ascertain the importance of inflammation in IR among obese adolescents by utilizing either random forest (RF) classification or mediation analysis approaches. The inflammation balance score, composed of eight pro- and anti-inflammatory makers, as well as most of the individual inflammatory markers differed significantly between lean and overweight/obese. In contrast, adiponectin was the only individual marker selected as a predictor of IR by RF, and the balance score only revealed a medium-to-low importance score. Neither adiponectin nor the inflammation balance score was found to mediate the relationship between obesity and IR. These findings do not support the premise that low-grade systemic inflammation is a key for the expression of IR in the human. Prospective longitudinal studies should confirm these findings.

  17. SORLA facilitates insulin receptor signaling in adipocytes and exacerbates obesity

    PubMed Central

    Schmidt, Vanessa; Schulz, Nadja; Yan, Xin; Schürmann, Annette; Kempa, Stefan; Kern, Matthias; Blüher, Matthias; Poy, Matthew N.

    2016-01-01

    In humans, genetic variation of sortilin-related receptor, L(DLR class) A repeats containing (SORL1), which encodes the intracellular sorting receptor SORLA, is a major genetic risk factor for familial and sporadic forms of Alzheimer’s disease. Recent GWAS analysis has also associated SORL1 with obesity in humans and in mouse models, suggesting that this receptor may play a role in regulating metabolism. Here, using mouse models with genetic loss or tissue-specific overexpression of SORLA as well as data from obese human subjects, we observed a gene-dosage effect that links SORLA expression to obesity and glucose tolerance. Overexpression of human SORLA in murine adipose tissue blocked hydrolysis of triacylglycerides and caused excessive adiposity. In contrast, Sorl1 gene inactivation in mice accelerated breakdown of triacylglycerides in adipocytes and protected animals from diet-induced obesity. We then identified the underlying molecular mechanism whereby SORLA promotes insulin-induced suppression of lipolysis in adipocytes. Specifically, we determined that SORLA acts as a sorting factor for the insulin receptor (IR) that redirects internalized receptor molecules from endosomes to the plasma membrane, thereby enhancing IR surface expression and strengthening insulin signal reception in target cells. Our findings provide a molecular mechanism for the association of SORL1 with human obesity and confirm a genetic link between neurodegeneration and metabolism that converges on the receptor SORLA. PMID:27322061

  18. Relationship between overall and abdominal obesity and periodontal disease among young adults.

    PubMed

    Amin, H El-Sayed

    2010-04-01

    To assess overall and abdominal obesity and their relation to periodontal disease among young adults, body mass index (BMI) and waist circumference (WC) were measured and clinical attachment loss (CAL), gingival index (GI) and Community Periodontal Index (CPI) were estimated. The sample comprised 380 adults (170 males and 210 females) aged 20-26 years. There was a significant correlation between both BMI and WC and CAL, GI and CPI in females. In males, a significant correlation was only recorded between WC and GI and CPI. Overall and abdominal obesity in young adult females and abdominal obesity in males were significantly associated with periodontal disease.

  19. Lowering body weight in obese mice with diastolic heart failure improves cardiac insulin sensitivity and function: implications for the obesity paradox.

    PubMed

    Sankaralingam, Sowndramalingam; Abo Alrob, Osama; Zhang, Liyan; Jaswal, Jagdip S; Wagg, Cory S; Fukushima, Arata; Padwal, Raj S; Johnstone, David E; Sharma, Arya M; Lopaschuk, Gary D

    2015-05-01

    Recent studies suggest improved outcomes and survival in obese heart failure patients (i.e., the obesity paradox), although obesity and heart failure unfavorably alter cardiac function and metabolism. We investigated the effects of weight loss on cardiac function and metabolism in obese heart failure mice. Obesity and heart failure were induced by feeding mice a high-fat (HF) diet (60% kcal from fat) for 4 weeks, following which an abdominal aortic constriction (AAC) was produced. Four weeks post-AAC, mice were switched to a low-fat (LF) diet (12% kcal from fat; HF AAC LF) or maintained on an HF (HF AAC HF) for a further 10 weeks. After 18 weeks, HF AAC LF mice weighed less than HF AAC HF mice. Diastolic function was improved in HF AAC LF mice, while cardiac hypertrophy was decreased and accompanied by decreased SIRT1 expression, increased FOXO1 acetylation, and increased atrogin-1 expression compared with HF AAC HF mice. Insulin-stimulated glucose oxidation was increased in hearts from HF AAC LF mice, compared with HF AAC HF mice. Thus lowering body weight by switching to LF diet in obese mice with heart failure is associated with decreased cardiac hypertrophy and improvements in both cardiac insulin sensitivity and diastolic function, suggesting that weight loss does not negatively impact heart function in the setting of obesity.

  20. Obesity and cancer, a case for insulin signaling

    PubMed Central

    Poloz, Y; Stambolic, V

    2015-01-01

    Obesity is a worldwide epidemic, with the number of overweight and obese individuals climbing from just over 500 million in 2008 to 1.9 billion in 2014. Type 2 diabetes (T2D), cardiovascular disease and non-alcoholic fatty liver disease have long been associated with the obese state, whereas cancer is quickly emerging as another pathological consequence of this disease. Globally, at least 2.8 million people die each year from being overweight or obese. It is estimated that by 2020 being overweight or obese will surpass the health burden of tobacco consumption. Increase in the body mass index (BMI) in overweight (BMI>25 kg/m2) and obese (BMI>30 kg/m2) individuals is a result of adipose tissue (AT) expansion, which can lead to fat comprising >50% of the body weight in the morbidly obese. Extensive research over the last several years has painted a very complex picture of AT biology. One clear link between AT expansion and etiology of diseases like T2D and cancer is the development of insulin resistance (IR) and hyperinsulinemia. This review focuses on defining the link between obesity, IR and cancer. PMID:26720346

  1. mRNA concentrations of MIF in subcutaneous abdominal adipose cells are associated with adipocyte size and insulin action

    PubMed Central

    Koska, Juraj; Stefan, Norbert; Dubois, Severine; Trinidad, Cathy; Considine, Robert V.; Funahashi, Tohru; Bunt, Joy C.; Ravussin, Eric; Permana, Paska A.

    2009-01-01

    Objective To determine whether the mRNA concentrations of inflammation response genes in isolated adipocytes and in cultured preadipocytes are related to adipocyte size and in vivo insulin action in obese individuals. Design Cross-sectional inpatient study. Subjects Obese Pima Indians with normal glucose tolerance. Measurements Adipocyte diameter (by microscope technique; n=29), expression of candidate genes (by quantitative real-time PCR) in freshly isolated adipocytes (monocyte chemoattractant protein [MCP] 1 and MCP2, macrophage inflammatory protein [MIP] 1α, MIP1β and MIP2, macrophage migration inhibitory factor [MIF], tumor necrosis factor alpha, interleukin [IL] 6 and IL8; n=22) and cultured preadipocytes (MCP1, MIP1α, MIF, IL6 and matrix metalloproteinase 2; n=33) from subcutaneous abdominal adipose tissue (by aspiration biopsy, n=34), body fat by dual-energy X-ray absorptiometry, glucose tolerance by 75-gram oral glucose tolerance test, and insulin action by euglycemic-hyperinsulinemic clamp (insulin infusion rate 40 mU/m2.min)(all n=34). Results MIF was the only gene whose expression in both freshly isolated adipocytes and cultured preadipocytes was positively associated with adipocytes diameter and negatively associated with peripheral and hepatic insulin action (all P<0.05). In multivariate analysis, the association between adipocyte MIF mRNA concentrations and adipocytes diameter was independent of percent body fat (P=0.03), whereas adipocyte MIF mRNA concentrations but not adipocytes diameter independently predicted peripheral insulin action. The mRNA expression concentrations of MIF gene in adipocytes were not associated with plasma concentrations of MIF, but were negatively associated with plasma adiponectin concentrations (P=0.004). In multivariate analysis, adipocyte MIF RNA concentrations (P=0.03) but not plasma adiponectin concentrations (P=0.4) remained a significant predictor of insulin action. Conclusions Increased expression of MIF gene in

  2. Traumatic brain injury and obesity induce persistent central insulin resistance.

    PubMed

    Karelina, Kate; Sarac, Benjamin; Freeman, Lindsey M; Gaier, Kristopher R; Weil, Zachary M

    2016-04-01

    Traumatic brain injury (TBI)-induced impairments in cerebral energy metabolism impede tissue repair and contribute to delayed functional recovery. Moreover, the transient alteration in brain glucose utilization corresponds to a period of increased vulnerability to the negative effects of a subsequent TBI. In order to better understand the factors contributing to TBI-induced central metabolic dysfunction, we examined the effect of single and repeated TBIs on brain insulin signalling. Here we show that TBI induced acute brain insulin resistance, which resolved within 7 days following a single injury but persisted until 28 days following repeated injuries. Obesity, which causes brain insulin resistance and neuroinflammation, exacerbated the consequences of TBI. Obese mice that underwent a TBI exhibited a prolonged reduction of Akt (also known as protein kinase B) signalling, exacerbated neuroinflammation (microglial activation), learning and memory deficits, and anxiety-like behaviours. Taken together, the transient changes in brain insulin sensitivity following TBI suggest a reduced capacity of the injured brain to respond to the neuroprotective and anti-inflammatory actions of insulin and Akt signalling, and thus may be a contributing factor for the damaging neuroinflammation and long-lasting deficits that occur following TBI.

  3. Lipogenic potential of liver from morbidly obese patients with and without non-insulin-dependent diabetes

    SciTech Connect

    Barakat, H.A.; McLendon, V.D.; Carpenter, J.W.; Marks, R.H.; Legett, N.; O'Brien, K.; Caro, J.F. )

    1991-03-01

    Intra-abdominal liver biopsies were obtained during surgery from fasted obese patients with non-insulin-dependent diabetes mellitus (NIDDM), obese normoglycemic controls, and lean controls. Lipid synthesis was studied in freshly isolated hepatocytes and liver homogenates from the three groups of subjects. Incorporation of 3H2O into the lipids of hepatocytes was determined in the absence and presence of insulin (0.1 mumol/L). The activities of five enzymes involved in fatty acid synthesis, and the incorporation of 14C-glycerol-3-phosphate into lipids were determined in liver homogenates. Basal lipid synthesis by hepatocytes was not different in the three groups of patients. Insulin stimulated lipogenesis by 8% +/- 30% in the lean controls, 33% +/- 8% in the obese controls and 17% +/- 6% in the NIDDM patients. No significant differences in the activities of the five enzymes that are involved in de novo fatty acid synthesis among the three groups of patients were observed. Similarly, incorporation of 14C-glycerol-3-phosphate by liver homogenates, in the presence of saturating or submaximal concentrations of fatty acids, did not differ among the three groups. These results show that under the experimental conditions of this study, including the fasted state of the patients, the basal capacity of liver of NIDDM patients to synthesize fatty acids or glycerides is the same as that of liver from obese and lean controls. Thus, it is likely that an increase in fatty acid flux into a liver with normal lipogenic potential may contribute to the increased synthesis of triglycerides by the liver of these patients in vivo.

  4. Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women.

    PubMed

    Stull, April J; Cash, Katherine C; Johnson, William D; Champagne, Catherine M; Cefalu, William T

    2010-10-01

    Dietary supplementation with whole blueberries in a preclinical study resulted in a reduction in glucose concentrations over time. We sought to evaluate the effect of daily dietary supplementation with bioactives from blueberries on whole-body insulin sensitivity in men and women. A double-blinded, randomized, and placebo-controlled clinical study design was used. After screening to resolve study eligibility, baseline (wk 0) insulin sensitivity was measured on 32 obese, nondiabetic, and insulin-resistant subjects using a high-dose hyperinsulinemic-euglycemic clamp (insulin infusion of 120 mU(861 pmol)⋅m(-2)⋅min(-1)). Serum inflammatory biomarkers and adiposity were measured at baseline. At the end of the study, insulin sensitivity, inflammatory biomarkers, and adiposity were reassessed. Participants were randomized to consume either a smoothie containing 22.5 g blueberry bioactives (blueberry group, n = 15) or a smoothie of equal nutritional value without added blueberry bioactives (placebo group, n = 17) twice daily for 6 wk. Both groups were instructed to maintain their body weight by reducing ad libitum intake by an amount equal to the energy intake of the smoothies. Participants' body weights were evaluated weekly and 3-d food records were collected at baseline, the middle, and end of the study. The mean change in insulin sensitivity improved more in the blueberry group (1.7 ± 0.5 mg⋅kg FFM(-1)⋅min(-1)) than in the placebo group (0.4 ± 0.4 mg⋅kg FFM(-1)⋅min(-1)) (P = 0.04). Insulin sensitivity was enhanced in the blueberry group at the end of the study without significant changes in adiposity, energy intake, and inflammatory biomarkers. In conclusion, daily dietary supplementation with bioactives from whole blueberries improved insulin sensitivity in obese, nondiabetic, and insulin-resistant participants.

  5. [Obesity, inflammation and insulin resistance: which role for adipokines].

    PubMed

    Antuna-Puente, Barbara; Feve, Bruno; Fellahi, Soraya; Bastard, Jean-Philippe

    2007-01-01

    Adipose tissue is now recognized as an endocrine organ involved in regulating physiologic and pathologic processes including inflammation. It synthesizes and secretes hormones such as leptin and adiponectin. It can secrete other products namely adipokines including cytokines and chemokines. The release of adipokines by either adipocytes or adipose tissue-infiltrated macrophages leads to a chronic sub-inflammatory state that likely plays a major role in cardiovascular complications linked to obesity and insulin resistance.

  6. Intra-abdominal fat is related to metabolic syndrome and non-alcoholic fat liver disease in obese youth

    PubMed Central

    2013-01-01

    Background Previous studies have shown an association between adiposity, especially intra-abdominal adipose tissue, and hemodynamic/metabolic comorbidities in adults, however it is not clear in pediatric population. The aim of the study was to analyze the relationship between non-alcoholic fatty liver disease (NAFLD) and components of metabolic syndrome (MS) with values of intra-abdominal (IAAT) and subcutaneous (SCAT) adipose tissue in obese children and adolescents. Methods Cross-sectional study. Subjects: 182 obese sedentary children and adolescents (aged 6 to 16 y), identified by the body mass index (BMI). Measurements: Body composition and trunk fat by dual-energy X-ray absorptiometry- DXA; lipid profile, blood pressure and pubertal stage were also assessed. NAFLD was classified as absent (0), mild (1), moderate (2) and severe (3), and intra-abdominal and subcutaneous abdominal fat thickness were identified by ultrasound. The MS was identified according to the cut offs proposed by World Health Organization adapted for children and adolescents. The chi-square test was used to compare categorical variables, and the binary logistic regression indicated the magnitude of the associations adjusted by potential cofounders (sex, age, maturation, NAFLD and HOMA-IR). Results Higher quartile of SCAT was associated with elevated blood pressure (p = 0.015), but not associated with NAFLD (p = 0.665). Higher IAAT was positively associated with increased dyslipidemia (p = 0.001), MS (p = 0.013) and NAFLD (p = 0.005). Intermediate (p = 0.007) and highest (p = 0.001) quartile of IAAT were also associated with dyslipidemia, independently of age, sex, maturation, NAFLD and HOMA-IR (homeostatic model assessment-insulin resistance). Conclusion Obese children and adolescents, with higher IAAT are more prone to develop MS and NAFLD than those with higher values of SCAT, independent of possible confounding variables. PMID:23919592

  7. Insulin Resistance in Young Obese Subjects and Its Relation to Smoking (A Pilot Study).

    PubMed

    Juneja, Aarzoo; Dwivedi, Shridhar; Srivastava, D K; Chandra, Kailash

    2017-03-01

    Insulin resistance is a condition in which cells fail to respond to the normal actions of insulin. Dietary fat, obesity and smoking have been attributed to increase insulin resistance. However, the prevalence of insulin resistance in young obese subjects and its relation to smoking is not well established. This study comprising seventy-five healthy young adults was undertaken to find insulin resistance in obese smokers and non smokers both. Present study showed an overall prevalence of raised homeostatic model assessment of insulin resistance in 14.7 % otherwise healthy young subjects (20-30 years age group). Non-smokers did not show any significant correlation between insulin resistance and body mass index at either stage (normal, pre-obese as well as obese). Smokers also did not show any significant difference of insulin resistance in normal and pre-obese stages. However, marked increase in homeostatic model assessment of insulin resistance was observed in obese smokers. Homeostatic model assessment of insulin resistance showed a linear trend in relation to body mass index and its values were found to be higher in smokers. Obesity combined with smoking demonstrated statistically significant increase in homeostatic model assessment of insulin resistance.

  8. Adipocytokine Profile and Insulin Resistance in Childhood Obesity

    PubMed Central

    GHERLAN, Iuliana; VLADOIU, Suzana; ALEXIU, Florin; GIURCANEANU, Mihaela; OROS, Sabina; BREHAR, Andreea; PROCOPIUC, Camelia; DUMITRACHE, Constantin

    2012-01-01

    ABSTRACT Background: Adipose tissue is a veritable "endocrine organ" due to its adipocytokines secretion implied in insulin sensitivity modulation and cardiovascular complications. Objective: To identify the adipocytokines' plasmatic profile (adiponectin, leptin, resistin, IL-6, TNFα) in obese children and adolescents and to assess their relationship with "classic" clinical/paraclinical markers of metabolic syndrome and insulin resistance. Material and Methods: A case-control study comparing a study group of 38 obese children and adolescents (age 13.5±2.3 years) to a normal weight age matched control group of 24 children. We measured body mass index (BMI) and waist circumference (WC), systolic and diastolic blood pressure (BP). The classical metabolic parameters (fasting glycemia, total cholesterol and its fractions, serum triglycerides) were measured in both groups. Insulin sensitivity was evaluated using fasting insulinemia, HOMA-index and insulin-resistance summary score (IRS). Adiponectin, leptin, resistin, IL-6 and TNFα were measured using ELISA method. Outcomes: Serum levels of leptin, resistin and IL-6 were signficantly higher (42.42±22.58 ng/ml versus 14.4±14.49 ng/ml, p <0.001; 9.69±3.47 ng/ml versus 7.92±2.13ng/ml, p = 0.029 and 2.66 ±2.87 pg/ml versus 0.89 ± 1.16 pg/ml, p = 0.006 respectively), while adiponectin levels were significantly lower (9.05±4.61 µg/ml versus 15.93±9.24 μg/ml, p <0.001) in the obese group compared to control group. TNFα was not statistical different between groups. In multivariate regression analysis adiponectin was negatively and significantly correlated with WC (r = - 0.463, p = 0.003); leptin was positively and significantly related to WC, diastolic BP, fasting insulinemia and resistin (r = 0.775, p <0.001); resistin was positively related to leptin and IL-6 (r = 0.499, p <0.001), IL-6 was positively and significantly related to diastolic blood pressure (r = 0.333, p = 0.008). Conclusions: Serum levels of

  9. Chromogranin A Regulation of Obesity and Peripheral Insulin Sensitivity

    PubMed Central

    Bandyopadhyay, Gautam K.; Mahata, Sushil K.

    2017-01-01

    Chromogranin A (CgA) is a prohormone and granulogenic factor in endocrine and neuroendocrine tissues, as well as in neurons, and has a regulated secretory pathway. The intracellular functions of CgA include the initiation and regulation of dense-core granule biogenesis and sequestration of hormones in neuroendocrine cells. This protein is co-stored and co-released with secreted hormones. The extracellular functions of CgA include the generation of bioactive peptides, such as pancreastatin (PST), vasostatin, WE14, catestatin (CST), and serpinin. CgA knockout mice (Chga-KO) display: (i) hypertension with increased plasma catecholamines, (ii) obesity, (iii) improved hepatic insulin sensitivity, and (iv) muscle insulin resistance. These findings suggest that individual CgA-derived peptides may regulate different physiological functions. Indeed, additional studies have revealed that the pro-inflammatory PST influences insulin sensitivity and glucose tolerance, whereas CST alleviates adiposity and hypertension. This review will focus on the different metabolic roles of PST and CST peptides in insulin-sensitive and insulin-resistant models, and their potential use as therapeutic targets. PMID:28228748

  10. Myeloid cell-restricted insulin receptor deficiency protects against obesity-induced inflammation and systemic insulin resistance.

    PubMed

    Mauer, Jan; Chaurasia, Bhagirath; Plum, Leona; Quast, Thomas; Hampel, Brigitte; Blüher, Matthias; Kolanus, Waldemar; Kahn, C Ronald; Brüning, Jens C

    2010-05-06

    A major component of obesity-related insulin resistance is the establishment of a chronic inflammatory state with invasion of white adipose tissue by mononuclear cells. This results in the release of pro-inflammatory cytokines, which in turn leads to insulin resistance in target tissues such as skeletal muscle and liver. To determine the role of insulin action in macrophages and monocytes in obesity-associated insulin resistance, we conditionally inactivated the insulin receptor (IR) gene in myeloid lineage cells in mice (IR(Deltamyel)-mice). While these animals exhibit unaltered glucose metabolism on a normal diet, they are protected from the development of obesity-associated insulin resistance upon high fat feeding. Euglycemic, hyperinsulinemic clamp studies demonstrate that this results from decreased basal hepatic glucose production and from increased insulin-stimulated glucose disposal in skeletal muscle. Furthermore, IR(Deltamyel)-mice exhibit decreased concentrations of circulating tumor necrosis factor (TNF) alpha and thus reduced c-Jun N-terminal kinase (JNK) activity in skeletal muscle upon high fat feeding, reflecting a dramatic reduction of the chronic and systemic low-grade inflammatory state associated with obesity. This is paralleled by a reduced accumulation of macrophages in white adipose tissue due to a pronounced impairment of matrix metalloproteinase (MMP) 9 expression and activity in these cells. These data indicate that insulin action in myeloid cells plays an unexpected, critical role in the regulation of macrophage invasion into white adipose tissue and in the development of obesity-associated insulin resistance.

  11. Chromium picolinate enhances skeletal muscle cellular insulin signaling in vivo in obese, insulin-resistant JCR:LA-cp rats.

    PubMed

    Wang, Zhong Q; Zhang, Xian H; Russell, James C; Hulver, Matthew; Cefalu, William T

    2006-02-01

    Chromium is one of the few trace minerals for which a specific cellular mechanism of action has not been identified. Recent in vitro studies suggest that chromium supplementation may improve insulin sensitivity by enhancing insulin receptor signaling, but this has not been demonstrated in vivo. We investigated the effect of chromium supplementation on insulin receptor signaling in an insulin-resistant rat model, the JCR:LA-corpulent rat. Male JCR:LA-cp rats (4 mo of age) were randomly assigned to receive chromium picolinate (CrPic) (obese n=6, lean n=5) or vehicle (obese n=5, lean n=5) for 3 mo. The CrPic was provided in the water, and based on calculated water intake, rats randomized to CrPic received 80 microg/(kg.d). At the end of the study, skeletal muscle (vastus lateralis) biopsies were obtained at baseline and at 5, 15, and 30 min postinsulin stimulation to assess insulin signaling. Obese rats treated with CrPic had significantly improved glucose disposal rates and demonstrated a significant increase in insulin-stimulated phosphorylation of insulin receptor substrate (IRS)-1 and phosphatidylinositol (PI)-3 kinase activity in skeletal muscle compared with obese controls. The increase in cellular signaling was not associated with increased protein levels of the IRS proteins, PI-3 kinase or Akt. However, protein tyrosine phosphatase 1B (PTP1B) levels were significantly lower in obese rats administered CrPic than obese controls. When corrected for protein content, PTP1B activity was also significantly lower in obese rats administered CrPic than obese controls. Our data suggest that chromium supplementation of obese, insulin-resistant rats may improve insulin action by enhancing intracellular signaling.

  12. Insulin resistance in obesity and its molecular control.

    PubMed

    Noguchi, T; Tanaka, T

    1995-09-01

    The Wistar fatty rat is a model of obese non-insulin-dependent diabetes mellitus. Males, but not females, develop hyperglycemia, glucouria and polyuria within 8 weeks of age. The regulation of gene expression by insulin has been shown to be differentially impaired in the liver of the fatty rats. The genes resistant to insulin include glucokinase gene and phosphoenolpyruvate carboxykinase gene. In contrast, L-type pyruvate kinase gene responds to insulin normally, raising the possibility that the signaling pathway from the insulin receptor to the insulin-resistant genes, but not to the insulin-sensitive genes, is defective at a point beyond the receptor kinase in the fatty rats. On the other hand, female fatty rats develop hyperglycemia only when they are given sucrose for several weeks. This treatment causes a decrease in gucokinase while enzymes involved in gluconeogenesis are increased. Chronic feeding of sucrose also leads to hypertriglycemia and visceral fat accumulation, which is more frequently associated with abnormalities in glucose and lipid metabolisms. Fructose is believed to be the responsible component of sucrose for these effects. Hypertriglyceridemic effect of fructose is mainly due to an increase in hepatic production of VLDL. Most enzymes related to lipogenesis in the liver are induced by dietary fructose even in diabetes. L-type pyruvate kinase is one of such enzymes. Cis-acting element named PKL-III in the 5'-flanking region of this gene is shown to be responsive to dietary fructose as well as to dietary glucose. Thus, identification and characterization of a protein bound to this element could help in the further understanding of the molecular mechanism of the fructose actions.

  13. Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes.

    PubMed

    Malin, Steven K; Haus, Jacob M; Solomon, Thomas P J; Blaszczak, Alecia; Kashyap, Sangeeta R; Kirwan, John P

    2013-11-15

    Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance; however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization in adults with IFG, IGT, or IFG + IGT is unknown. Twenty-four older (66.7 ± 0.8 yr) obese (34.2 ± 0.9 kg/m(2)) adults were categorized as IFG (n = 8), IGT (n = 8), or IFG + IGT (n = 8) according to a 75-g oral glucose tolerance test (OGTT). Subjects underwent 12-wk of exercise (60 min/day for 5 days/wk at ∼85% HRmax) and were instructed to maintain a eucaloric diet. A euglycemic hyperinsulinemic clamp (40 mU·m(2)·min(-1)) with [6,6-(2)H]glucose was used to determine peripheral and hepatic insulin sensitivity. Nonoxidative glucose disposal and metabolic flexibility [insulin-stimulated respiratory quotient (RQ) minus fasting RQ] were also assessed. Glucose incremental area under the curve (iAUCOGTT) was calculated from the OGTT. Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than with IFG + IGT (P < 0.05). Exercise reduced glucose iAUCOGTT in IGT only (P < 0.05), and the decrease in glucose iAUCOGTT was inversely correlated with the increase in peripheral but not hepatic insulin sensitivity (P < 0.01). Increased clamp-derived peripheral insulin sensitivity was also correlated with enhanced metabolic flexibility, reduced fasting RQ, and higher nonoxidative glucose disposal (P < 0.05). Adults with IFG + IGT had smaller gains in clamp-derived peripheral insulin sensitivity and metabolic flexibility, which was related to blunted improvements in postprandial glucose. Additional work is required to assess the molecular mechanism(s) by which chronic hyperglycemia modifies insulin sensitivity following exercise training.

  14. Prevalence and secular changes in abdominal obesity in Canadian adolescents and adults, 1981 to 2007-2009.

    PubMed

    Janssen, I; Shields, M; Craig, C L; Tremblay, M S

    2011-06-01

    The purposes of this study were to: (i) provide contemporary estimates of the prevalence of abdominal obesity, as assessed by waist circumference (WC), in Canadian adolescents and adults; (ii) provide estimates of the prevalence of abdominal obesity within normal weight, overweight and obese body mass index categories and (iii) examine secular changes in abdominal obesity. Data were based on three national health surveys conducted in 1981, 1988 and 2007-2009. WC was measured at the mid-point between the last rib and iliac crest in all three surveys. The prevalence of Canadians with abdominal obesity increased with age and was higher in females than in males. In 12- to 19-year-old adolescents, the estimated prevalence of abdominal obesity was 1.8% in 1981, 2.4% in 1988 and 12.8% in 2007-2009. The corresponding values for 20- to 69-year-old adults were 11.4%, 14.2% and 35.6%. Between 1981 and 2007-2009, mean WC values increased by 4.2 cm in adolescent males, 6.7 cm in adolescent females, 6.5 cm in men and 10.6 cm in women. Within the 2007-2009 survey, 2.6% of normal weight adults had abdominal obesity, 35.3% of overweight adults had abdominal obesity and 93.0% of obese adults had abdominal obesity.

  15. In non-obese girls waist circumference predicts insulin resistance is comparably to MRI fat measures and superior to BMI

    PubMed Central

    Wolfgram, Peter M.; Connor, Ellen L.; Rehm, Jennifer L.; Eickhoff, Jens C.; Zha, Wei; Reeder, Scott B.; Allen, David B.

    2015-01-01

    Objective To investigate the degree to which waist circumference (WC), BMI, and MRI measured abdominal fat deposition predict insulin resistance (IR) in non-obese girls of diverse racial and ethnic backgrounds. Methods Fifty-seven non-obese girls (12 African-American, 16 Hispanic White and 29 non-Hispanic White girls), aged 11–14 years old were assessed for WC, MRI hepatic proton density fat fraction, visceral and subcutaneous adipose tissue volume, BMI Z-score, fasting insulin, HOMA-IR, adiponectin, leptin, sex hormone binding globulin, HDL cholesterol, and triglycerides. Results Univariate and multivariate analyses adjusted for race and ethnicity indicated that only WC and visceral adipose tissue volume were independent predictors of fasting insulin and HOMA-IR, while dependent predictors were hepatic proton density fat fraction, BMI Z-score, and subcutaneous adipose tissue volume. Hispanic White girls showed significantly higher mean fasting insulin, HOMA-IR, and lower sex hormone binding globulin than non-Hispanic White girls (p-value <0.01). Conclusions In non-obese girls of diverse racial and ethnic backgrounds, WC, particularly when adjusted for race or ethnicity, is an independent predictor of IR comparable to MRI-derived measurements of fat and superior to BMI Z-score. PMID:26352642

  16. Amelioration of insulin resistance by rosiglitazone is associated with increased adipose cell size in obese type 2 diabetic patients

    PubMed Central

    Eliasson, Bjorn; Smith, Ulf; Mullen, Shawn; Cushman, Samuel W; Sherman, Arthur S; Yang, Jian

    2014-01-01

    Early studies reported that the size of adipose cells positively correlates with insulin resistance, but recent evidence suggests that the relationship between adipose cell size and insulin resistance is more complex. We previously reported that among BMI-matched moderately obese subjects who were either insulin sensitive or resistant insulin resistance correlated with the proportion of small adipose cells, rather than the size of the large adipose cells, whereas the size of large adipose cells was found to be a predictor of insulin resistance in the first-degree relatives of type 2 diabetic (T2D) patients. The relationship between adipose cellularity and insulin resistance thus appears to depend on the metabolic state of the individual. We did a longitudinal study with T2D patients treated with the insulin-sensitizer rosiglitazone to test the hypothesis that improved insulin sensitivity is associated with increased adipocyte size. Eleven T2D patients were recruited and treated with rosiglitazone for 90 days. Blood samples and needle biopsies of abdominal subcutaneous fat were taken at six time points and analyzed for cell size distributions. Rosiglitazone treatment ameliorated insulin resistance as evidenced by significantly decreased fasting plasma glucose and increased index of insulin sensitivity, QUICKI. In association with this, we found significantly increased size of the large adipose cells and, with a weaker effect, increased proportion of small adipose cells. We conclude rosiglitazone treatment both enlarges existing large adipose cells and recruits new small adipose cells in T2D patients, improving fat storage capacity in adipose tissue and thus systemic insulin sensitivity. PMID:26317056

  17. Bariatric Surgery in Morbidly Obese Insulin Resistant Humans Normalises Insulin Signalling but Not Insulin-Stimulated Glucose Disposal

    PubMed Central

    de Berker, David A. R.; May, Margaret T.; Hers, Ingeborg; Dayan, Colin M.; Andrews, Robert C.; Tavaré, Jeremy M.

    2015-01-01

    Aims Weight-loss after bariatric surgery improves insulin sensitivity, but the underlying molecular mechanism is not clear. To ascertain the effect of bariatric surgery on insulin signalling, we examined glucose disposal and Akt activation in morbidly obese volunteers before and after Roux-en-Y gastric bypass surgery (RYGB), and compared this to lean volunteers. Materials and Methods The hyperinsulinaemic euglycaemic clamp, at five infusion rates, was used to determine glucose disposal rates (GDR) in eight morbidly obese (body mass index, BMI=47.3±2.2 kg/m2) patients, before and after RYGB, and in eight lean volunteers (BMI=20.7±0.7 kg/m2). Biopsies of brachioradialis muscle, taken at fasting and insulin concentrations that induced half-maximal (GDR50) and maximal (GDR100) GDR in each subject, were used to examine the phosphorylation of Akt-Thr308, Akt-473, and pras40, in vivo biomarkers for Akt activity. Results Pre-operatively, insulin-stimulated GDR was lower in the obese compared to the lean individuals (P<0.001). Weight-loss of 29.9±4 kg after surgery significantly improved GDR50 (P=0.004) but not GDR100 (P=0.3). These subjects still remained significantly more insulin resistant than the lean individuals (p<0.001). Weight loss increased insulin-stimulated skeletal muscle Akt-Thr308 and Akt-Ser473 phosphorylation, P=0.02 and P=0.03 respectively (MANCOVA), and Akt activity towards the substrate PRAS40 (P=0.003, MANCOVA), and in contrast to GDR, were fully normalised after the surgery (obese vs lean, P=0.6, P=0.35, P=0.46, respectively). Conclusions Our data show that although Akt activity substantially improved after surgery, it did not lead to a full restoration of insulin-stimulated glucose disposal. This suggests that a major defect downstream of, or parallel to, Akt signalling remains after significant weight-loss. PMID:25876175

  18. [Relationship between obesity, inflammation and insulin resistance: new concepts].

    PubMed

    Fève, Bruno; Bastard, Jean-Philippe; Vidal, Hubert

    2006-08-01

    White adipose tissue is the main site of energy storage, but it is now recognized as an active participant in regulating physiologic and pathologic processes including immunity and inflammation. It has an endocrine function by secreting at least two main hormones, leptin and adiponectin. It can secrete other products, named adipokines, including cytokines and chemokines, involved in inflammation process. The release of adipokines by either adipocytes or adipose tissue infiltrated macrophages lead to a chronic sub-inflammatory state that could play a central role in cardiovascular complications linked to obesity and insulin resistance, a risk factor to develop type-2 diabetes.

  19. Association between meal intake behaviour and abdominal obesity in Spanish adults.

    PubMed

    Keller, Kristin; Rodríguez López, Santiago; Carmenate Moreno, Margarita M

    2015-09-01

    The study aims to evaluate the association between abdominal obesity with meal intake behaviour such as having a forenoon meal, having an afternoon meal and snacking. This cross-sectional study includes n = 1314 participants aged 20-79 who were interviewed during the Cardiac health "Semanas del Corazon" events in four Spanish cities (Madrid, Las Palmas, Seville and Valencia) in 2008. Waist circumference, weight and height were assessed to determine abdominal obesity (waist circumference: ≥88 cm in women and ≥102 cm in men) and BMI, respectively. The intake of forenoon and afternoon meal and snacking between the participants' regular meals were assessed with a questionnaire that also included individual risk factors. The information obtained about diet was required to calculate an Unhealthy Habit Score and a score reflecting the Achievement of Dietary Guidelines. Adjusted logistic regressions were used to examine the association between abdominal obesity and the mentioned meal intake behaviour controlling for sex, age, individual risk factors, BMI and diet. Having an afternoon meal (OR 0.60; 95% CI (0.41-0.88)) was negatively associated with abdominal obesity after adjusting for all confounders, whereas the positive association of snacking (OR 1.39; 95% CI (1.05-1.85)) was not independent of BMI (OR 1.25; 95% CI (0.84-1.87)). Taking a forenoon meal did not show any associations (OR 0.92; 95% CI (0.63-1.34)) with abdominal obesity. The results obtained could be helpful in the promotion of healthy habits in nutritional education programmes and also in health programmes preventing abdominal obesity.

  20. Prevalence of abdominal obesity in adolescents: association between sociodemographic factors and lifestyle

    PubMed Central

    Castro, João Antônio Chula; Nunes, Heloyse Elaine Gimenes; Silva, Diego Augusto Santos

    2016-01-01

    Abstract Objective: To estimate the prevalence of abdominal obesity and verify the association with sociodemographic factors (gender, school shift, ethnicity, age, maternal education and economic status) and lifestyle (alcohol consumption, sleep, soft drink consumption, level of physical activity and sedentary behavior) in adolescents in Southern Brazil. Methods: This was a cross-sectional epidemiological study of 930 adolescents (490 girls) aged 14–19 years, living in the city of São José, SC, Brazil. A self-administered questionnaire was used to collect sociodemographic and lifestyle data. Abdominal obesity was measured through the waist circumference and analyzed according to gender and age. Descriptive statistics (absolute and relative frequency, mean and standard deviation) and binary logistic regression, expressed as Odds Ratios (OR) and 95% confidence interval (95%CI) were employed, with p<0.05 being considered statistically significant; the SPSS 17.0 software was used for the statistical analyses. Results: The prevalence of abdominal obesity was 10.6% for the total sample (10.5% male, 10.8% female). Adolescents that watched television daily for two or more hours (OR=2.11, 95%CI 1.08–4.13) had a higher chance of having abdominal obesity and adolescents whose mothers had fewer than eight years of schooling (OR=0.56; 95%CI from 0.35 to 0.91) had a lower chance of having abdominal obesity. Conclusions: Approximately one in 10 adolescents had abdominal obesity; the associated factors were maternal schooling (≥8 years) and television screen time (≥2h/day). PMID:26993748

  1. Interacting epidemics? Sleep curtailment, insulin resistance, and obesity

    PubMed Central

    Lucassen, Eliane A; Rother, Kristina I; Cizza, Giovanni

    2012-01-01

    In the last 50 years, the average self-reported sleep duration in the United States has decreased by 1.5–2 hours in parallel with an increasing prevalence of obesity and diabetes. Epidemiological studies and meta-analyses report a strong relationship between short or disturbed sleep, obesity, and abnormalities in glucose metabolism. This relationship is likely to be bidirectional and causal in nature, but many aspects remain to be elucidated. Sleep and the internal circadian clock influence a host of endocrine parameters. Sleep curtailment in humans alters multiple metabolic pathways, leading to more insulin resistance, possibly decreased energy expenditure, increased appetite, and immunological changes. On the other hand, psychological, endocrine, and anatomical abnormalities in individuals with obesity and/or diabetes can interfere with sleep duration and quality, thus creating a vicious cycle. In this review, we address mechanisms linking sleep with metabolism, highlight the need for studies conducted in real-life settings, and explore therapeutic interventions to improve sleep, with a potential beneficial effect on obesity and its comorbidities. PMID:22827862

  2. Obesity-related insulin resistance: implications for the surgical patient.

    PubMed

    Tewari, N; Awad, S; Macdonald, I A; Lobo, D N

    2015-11-01

    In healthy surgical patients, preoperative fasting and major surgery induce development of insulin resistance (IR). IR can be present in up to 41% of obese patients without diabetes and this can rise in the postoperative period, leading to an increased risk of postoperative complications. Inflammation is implicated in the aetiology of IR. This review examines obesity-associated IR and its implications for the surgical patient. Searches of the Medline and Science Citation Index databases were performed using various key words in combinations with the Boolean operators AND, OR and NOT. Key journals, nutrition and metabolism textbooks and the reference lists of key articles were also hand searched. Adipose tissue has been identified as an active endocrine organ and the chemokines secreted as a result of macrophage infiltration have a role in the pathogenesis of IR. Visceral adipose tissue appears to be the most metabolically active, although results across studies are not consistent. Results from animal and human studies often provide conflicting results, which has rendered the pursuit of a common mechanistic pathway challenging. Obesity-associated IR appears, in part, to be related to inflammatory changes associated with increased adiposity. Postoperatively, the surgical patient is in a proinflammatory state, so this finding has important implications for the obese surgical patient.

  3. Interacting epidemics? Sleep curtailment, insulin resistance, and obesity.

    PubMed

    Lucassen, Eliane A; Rother, Kristina I; Cizza, Giovanni

    2012-08-01

    In the last 50 years, the average self-reported sleep duration in the United States has decreased by 1.5-2 hours in parallel with an increasing prevalence of obesity and diabetes. Epidemiological studies and meta-analyses report a strong relationship between short or disturbed sleep, obesity, and abnormalities in glucose metabolism. This relationship is likely to be bidirectional and causal in nature, but many aspects remain to be elucidated. Sleep and the internal circadian clock influence a host of endocrine parameters. Sleep curtailment in humans alters multiple metabolic pathways, leading to more insulin resistance, possibly decreased energy expenditure, increased appetite, and immunological changes. On the other hand, psychological, endocrine, and anatomical abnormalities in individuals with obesity and/or diabetes can interfere with sleep duration and quality, thus creating a vicious cycle. In this review, we address mechanisms linking sleep with metabolism, highlight the need for studies conducted in real-life settings, and explore therapeutic interventions to improve sleep, with a potential beneficial effect on obesity and its comorbidities.

  4. Hepatocyte Toll-like receptor 4 regulates obesity-induced inflammation and insulin resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic low-grade inflammation is a hallmark of obesity and thought to contribute to the development of obesity-related insulin resistance. Toll-like receptor 4 (Tlr4) is a key mediator of pro-inflammatory responses. Mice lacking Tlr4s are protected from diet-induced insulin resistance and inflammat...

  5. Impact of obstructive sleep apnoea on insulin resistance in nonobese and obese children.

    PubMed

    Koren, Dorit; Gozal, David; Philby, Mona F; Bhattacharjee, Rakesh; Kheirandish-Gozal, Leila

    2016-04-01

    Obstructive sleep apnoea (OSA) has been inconsistently associated with insulin resistance and adverse metabolic states. We aimed to assess independent contributions of OSA to insulin resistance and dyslipidaemia in a large paediatric cohort.Habitually snoring children underwent overnight polysomnography, anthropometric measurements and fasting laboratory evaluations. Primary outcome measures included insulin, glucose, homeostasis model of insulin resistance, lipoproteins and sleep disturbance measures.Among 459 children aged 5-12 years, obesity was the primary driver of most associations between OSA and metabolic measures, but sleep duration was inversely associated with glucose levels, with N3 and rapid eye movement (REM) sleep being negatively associated and sleep fragmentation positively associated with insulin resistance measures. In children with mild OSA, the presence of obesity increased the odds for insulin resistance, while higher apnoea/hypopnoea index values emerged among obese children who were more insulin-resistant.The exclusive presence of interactions between OSA and obesity in the degree of insulin resistance is coupled with synergistic contributions by sleep fragmentation to insulin resistance in the context of obesity. Insufficient N3 or REM sleep may also contribute to higher glycaemia independently of obesity. Studies are needed to better delineate the roles of puberty and sleep fragmentation in insulin resistance and the metabolic syndrome.

  6. Insulin resistance modifies the association between obesity and current asthma in adults.

    PubMed

    Cardet, Juan Carlos; Ash, Samuel; Kusa, Tope; Camargo, Carlos A; Israel, Elliot

    2016-08-01

    Insulin resistance potentiates the association between obesity and childhood asthma, but this relationship appears inconsistent in relatively small studies of adults. We investigated effect modification in adults using the National Health and Nutrition Examination Survey 2003-2012, a large, nationally representative database.Insulin resistance and a history of physician-diagnosed current asthma were obtained from 12 421 adults, ages 18-85 years. We used logistic regression to determine associations between obesity and current asthma, adjusting for age, sex, race/ethnicity, poverty income ratio and smoking status. An interaction term evaluated effect modification by insulin resistance of the obesity-asthma association.As expected, obesity was positively associated with current asthma. Insulin resistance modified this association, with obesity measured as body mass index, waist circumference or waist-to-height ratio. The relationship between obesity and current asthma was stronger with increasing insulin resistance tertiles (OR 2.05, 95% CI 2.76-3.00; p-value for interaction 0.03). This association was robust to adjustments for other components of the metabolic syndrome (hypertriglyceridaemia, hypertension, hyperglycaemia and systemic inflammation). None of these components were themselves effect modifiers of the obesity-asthma association.In this large, nationally representative sample, insulin resistance modified the association between obesity and current asthma in adults. Targeting insulin resistance may represent a novel therapeutic strategy for obese patients with asthma.

  7. The relationship between job enrichment and abdominal obesity: a longitudinal field study of apparently healthy individuals.

    PubMed

    Fried, Yitzhak; Laurence, Gregory A; Shirom, Arie; Melamed, Samuel; Toker, Sharon; Berliner, Shlomo; Shapira, Itzhak

    2013-10-01

    Obesity has become an epidemic in modern society. However, there is a paucity of research about how job context affects obesity. To enhance our knowledge we used a large, heterogeneous sample of apparently healthy employees (n = 1,949) across two time periods with an average of close to 3.5 years between measures. We tested a hypothesized curvilinear effect of job enrichment on changes in two stress related indicators of abdominal obesity over time: waist circumference (WC) and waist-hip ratio (WHR). Job enrichment consisted of the job dimensions of variety, identity, significance, autonomy, and feedback, and in our analysis we controlled for demographics and health related behaviors, including weekly sports activity, number of cigarettes smoked per day, and weekly alcohol consumption. The results supported the hypothesized U-shaped relationship between job enrichment and changes in both indicators of abdominal obesity over time, such that the level of abdominal obesity was reduced when job enrichment was moderate and was increased when job enrichment was either high or low. As expected, no such association was observed for the general obesity measure of body mass index (BMI). We discuss the theoretical and practical implications of these results.

  8. Excess weight and abdominal obesity in postmenopausal Brazilian women: a population-based study

    PubMed Central

    2013-01-01

    Background The menopause is associated with a tendency to gain weight. Several alterations in fat deposits occur, leading to changes in the distribution of body fat. There are strong indications that, in middle age, obesity is associated with increased mortality. This study set out to determine the factors associated with the prevalence of overweight and abdominal obesity in postmenopausal women in a population-based study in Brazil. Methods The sample included 456 women, aged 45–69 years, residing in the urban area of Maringa, Parana. Systematic sampling, with a probability proportional to the size of the census sector, was performed. Behavioral, economic, and sociodemographic data were collected, and body mass index (BMI) and waist circumference (WC) were determined. Results According to BMI criteria (≥25.0 kg/m2), 72.6% of the women were overweight, and according to WC (≥88 cm), 63.6% had abdominal obesity. Based on logistic regression analysis, the factors that were most closely associated with overweight were: having three or more children (odds ratio (OR): 1.78; 95% confidence interval (CI): 1.06–3.00); and not taking hormone replacement therapy (OR: 1.69; 95% CI: 1.06–2.63). The prevalence of abdominal obesity was positively associated with greater parity (OR: 1.34, 95% CI: 1.05–1.72) and age older than 65 years (OR: 1.50; 95% CI: 1.03–2.19). Conclusions This study found that the prevalences of overweight and abdominal obesity were higher for postmenopausal women who had three or more children. Age over 65 years was also a risk factor for abdominal obesity and no use of hormonal replacement therapy was a risk factor for overweight. PMID:24228934

  9. Insulin resistance and endocrine-metabolic abnormalities in polycystic ovarian syndrome: Comparison between obese and non-obese PCOS patients

    PubMed Central

    Layegh, Parvin; Mousavi, Zohreh; Farrokh Tehrani, Donya; Parizadeh, Seyed Mohammad Reza; Khajedaluee, Mohammad

    2016-01-01

    Background: Insulin resistance has an important role in pathophysiology of polycystic ovarian syndrome (PCOS). Yet there are certain controversies regarding the presence of insulin resistance in non-obese patients. Objective: The aim was to compare the insulin resistance and various endocrine and metabolic abnormalities in obese and non-obese PCOS women. Materials and Methods: In this cross-sectional study which was performed from 2007-2010, 115 PCOS patients, aged 16-45 years were enrolled. Seventy patients were obese (BMI ≥25) and 45 patients were non-obese (BMI <25). Presence of insulin resistance and endocrine-metabolic abnormalities were compared between two groups. Collected data were analyzed with SPSS version 16.0 and p<0.05 was considered as statistically significant. Results: There was no significant difference in presence of insulin resistance (HOMA-IR >2.3) between two groups (p=0.357). Waist circumference (p<0.001), waist/hip ratio (p<0.001), systolic (p<0.001) and diastolic (p<0.001) blood pressures, fasting blood sugar (p=0.003) and insulin (p=0.011), HOMA-IR (p=0.004), total cholesterol (p=0.001) and triglyceride (p<0.001) were all significantly higher in obese PCOS patients. There was no significant difference in total testosterone (p=0.634) and androstenedione (p=0.736) between groups whereas Dehydroepiandrotendione sulfate (DHEAS) was significantly higher in non-obese PCOS women (p=0.018). There was no case of fatty liver and metabolic syndrome in non-obese patients, whereas they were seen in 31.3% and 39.4% of obese PCOS women, respectively. Conclusion: Our study showed that metabolic abnormalities are more prevalent in obese PCOS women, but adrenal axis activity that is reflected in higher levels of DHEAS was more commonly pronounced in our non-obese PCOS patients. PMID:27351028

  10. Association of Elevated Serum Uric Acid with the Components of Metabolic Syndrome and Oxidative Stress in Abdominal Obesity Subjects.

    PubMed

    Pingmuangkaew, Patcharin; Tangvarasittichai, Orathai; Tangvarasittichai, Surapon

    2015-07-01

    Abdominal obesity (AO) and metabolic syndrome (MetS) are associated with the cardiovascular disease and type 2 diabetes. Serum uric acid (SUA) is often elevated in subjects with the AO. We aimed to investigate the association of elevated SUA with the components of MetS, oxidative stress and TG/HDL-C ratio in AO subjects. This cross-sectional study used data from a Health Survey for Prevention of Hypertension and Type 2 Diabetes Mellitus in residents of two districts in Phitsanulok province, including 443 subjects. Anthropometric, blood pressure (BP) and biochemical variables were measured. We categorized the participants to two-group as 248 AO subjects (median age = 58, interquartile range 50.0-65.0 years) and 195 non-AO subjects (median age = 53, interquartile range 47.0-62.0 years). Waist circumference was significantly correlated with SystBP, DiastBP, Glu and SUA (P < 0.05) and SUA was significantly correlated with Glu, TG, HDL-C and TG/HDL-C ratio (P < 0.05). By using multiple logistic regression, we found the association of elevated SUA with abdominal obesity, hyperglycemia, hypertriglyceridemia, reduced HDL-C, elevated TG/HDL-C ratio, MetS and increased oxidative stress after adjusting for their covariates. Our study demonstrated that circulating UA is a major antioxidant and might help protect against free-radical oxidative damage. However, elevated SUA concentrations associated with oxidative stress, MetS, insulin resistance, and components of MetS. Then, SUA may be a marker of increased oxidative stress, insulin resistance and MetS, implying an increased risk of vascular disease and T2DM.

  11. CXCL5 is an adipose tissue derived factor that links obesity to insulin resistance

    PubMed Central

    Chavey, Carine; Lazennec, Gwendal; Lagarrigue, Sylviane; Clapé, Cyrielle; Iankova, Irena; Teyssier, Jacques; Annicotte, Jean-Sébastien; Schmidt, Julien; Mataki, Chikage; Yamamoto, Hiroyasu; Sanches, Rosario; Guma, Anna; Stich, Vladimir; Vitkova, Michaela; Jardin-Watelet, Bénédicte; Renard, Eric; Strieter, Robert; Tuthill, Antoinette; Hotamisligil, Gôkhan S.; Vidal-Puig, Toni; Zorzano, Antonio; Langin, Dominique; Fajas, Lluis

    2009-01-01

    We show here high levels of expression and secretion of the chemokine CXCL5 in the macrophage fraction of white adipose tissue (WAT). Moreover, we find that CXCL5 is dramatically increased in serum of human obese compared to lean subjects. Conversely, CXCL5 concentration is decreased in obese subjects after a weight reduction program, or in obese non-insulin resistant, compared to insulin resistant obese subjects. Most importantly we demonstrate that treatment with recombinant CXCL5 blocks insulin-stimulated glucose uptake in muscle in mice. CXCL5 blocks insulin signaling by activating the Jak2/STAT5/SOCS2 pathway. Finally, by treating obese, insulin resistant mice with either anti-CXCL5 neutralizing antibodies or antagonists of CXCR2, which is the CXCL5 receptor we demonstrate that CXCL5 mediates insulin resistance. Furthermore CXCR2−/− mice are protected against obesity-induced insulin resistance. Taken together, these results show that secretion of CXCL5 by WAT resident macrophages represents a link between obesity, inflammation, and insulin resistance. PMID:19356715

  12. Prevalence of obesity and abdominal obesity from four to 16 years old children living in the Mexico-USA border.

    PubMed

    Bacardí-Gascón, Montserrat; Jones, Elizabeth G; Jiménez-Cruz, Arturo

    2013-01-01

    The prevalence of obesity among Mexicans is alarming in both the child and adult populations. The objective of this study was to determine the levels of overweight, obesity and abdominal obesity in pre-school (PS), elementary (ES), and middle high (MHS) public school children from Tijuana. From February to April of 2011, a bietapic random sample was selected by cluster method of 30 PS, 30 ES, and 30 MHS children. And a sample of 30 groups for each level was chosen. Twenty elementary teachers and eight graduate students were trained at one central location on how to take anthropometric measurements using a portable scale, a stadiometer, and a measuring tape to determine weight, height, and waist circumference. Body Mass Index values were computed and compared to age/gender BMI percentiles according to WHO criteria. Waist circumference for-age at the 90th percentile from NHANES III (Mexican-American) was used to define abdominal obesity. The sample was composed of 646 PS children, 961 ES children, and 1,095 MHS children. Their ages ranged from 4- 16 years. Results showed an overall prevalence of overweight and obesity in younger than 5y preschool children (> 2 SD) of 23.1%, in ≥ 5 y PS (> 1 SD) of 33.8%, in ES children of 46.3%, and in MHS children of 41.9%. Abdominal obesity in PS children was 18%, in ES children was 16.7%, and in MHS children was 15.2%. These results warrant immediate and comprehensive actions to prevent a critical public health problem in Mexico.

  13. Weight-dependent differential contribution of insulin secretion and clearance to hyperinsulinemia of obesity.

    PubMed

    Erdmann, Johannes; Mayr, Martina; Oppel, Ulrich; Sypchenko, Oleg; Wagenpfeil, Stefan; Schusdziarra, Volker

    2009-01-08

    Obesity is associated with insulin resistance and the resulting hyperinsulinemia has been attributed to an increase of insulin secretion and a reduction of insulin clearance. The present study was intended to further characterize the relative contribution of secretion and clearance especially in the postprandial state. In relation to WHO body weight classes 291 subjects were divided in 5 subgroups Basal insulin concentrations rose stepwise and significantly with increasing BMI. This was paralleled by C-peptide concentrations and insulin secretion, while the reduction of insulin clearance was less stringent in relation to BMI. Basal glucose was unchanged in the BMI25 group and 8% higher in the obese groups (BMI 30, 35, 40) compared to normal weight (NW). Although postprandial insulin concentrations were significantly higher in the overweight and obese groups compared to NW the correlation was not as tight as in the basal state. Furthermore, the present data demonstrate for the first time that insulin secretion only increased in the overweight group without further augmentation in the obese groups. Further hyperinsulinemia of the latter was due to weight-dependent reduction of insulin clearance. The postprandial glucose response was 38-82% higher with increasing weight compared to NW. In summary basal hyperinsulinemia is mainly due to weight related increase of insulin secretion with moderate contribution of reduced insulin clearance. Postprandially, hyperinsulinemia of overweight is predominantly due to secretion while further postprandial hyperinsulinemia of obese subjects is mainly due to reduced clearance. Thus, postprandial insulin secretion cannot respond adequately to the challenge of weight-dependent insulin resistance already in non-diabetic obese subjects.

  14. Correlation between vitamin A, E, coenzyme Q10 and degree of insulin resistance in obese and non-obese subjects

    PubMed Central

    Mehmetoglu, Idris; Yerlikaya, F. Hümeyra; Kurban, Sevil

    2011-01-01

    The aim of the present study was to investigate correlation between plasma vitamin A, vitamin E, serum coenzyme Q10 levels and degree of insulin resistance in obese and normal weight people. The study was performed on 98 (21 Male, 77 Female) obese people and 78 (20 Male, 58 Female) control subjects. Vitamin A, E and coenzyme Q10 levels were adjusted to the lipid levels. Adjusted vitamin A and E and coenzyme Q10 levels of the obese female group were significantly lower than those of the control female group. Adjusted vitamin A and coenzyme Q10 levels of the obese male group were significantly lower than those of the control male group. Insulin resistance level of the obese female and male groups were significantly higher than that of the control female and male groups. There were no significant correlations between serum coenzyme Q10, plasma vitamin A and E levels and insulin resistance in obese and control subjects. Our findings show that it is essential to use the lipid adjusted levels of lipid soluble nutrients in obesity. Also, we have found no association between insulin resistance and vitamin A, vitamin E and coenzyme Q10 levels in obese subjects. PMID:22128213

  15. Quantification of Abdominal Fat in Obese and Healthy Adolescents Using 3 Tesla Magnetic Resonance Imaging and Free Software for Image Analysis

    PubMed Central

    Eloi, Juliana Cristina; Epifanio, Matias; de Gonçalves, Marília Maia; Pellicioli, Augusto; Vieira, Patricia Froelich Giora; Dias, Henrique Bregolin; Bruscato, Neide; Soder, Ricardo Bernardi; Santana, João Carlos Batista; Mouzaki, Marialena; Baldisserotto, Matteo

    2017-01-01

    Background and Aims Computed tomography, which uses ionizing radiation and expensive software packages for analysis of scans, can be used to quantify abdominal fat. The objective of this study is to measure abdominal fat with 3T MRI using free software for image analysis and to correlate these findings with anthropometric and laboratory parameters in adolescents. Methods This prospective observational study included 24 overweight/obese and 33 healthy adolescents (mean age 16.55 years). All participants underwent abdominal MRI exams. Visceral and subcutaneous fat area and percentage were correlated with anthropometric parameters, lipid profile, glucose metabolism, and insulin resistance. Student’s t test and Mann-Whitney’s test was applied. Pearson’s chi-square test was used to compare proportions. To determine associations Pearson’s linear correlation or Spearman’s correlation were used. Results In both groups, waist circumference (WC) was associated with visceral fat area (P = 0.001 and P = 0.01 respectively), and triglycerides were associated with fat percentage (P = 0.046 and P = 0.071 respectively). In obese individuals, total cholesterol/HDL ratio was associated with visceral fat area (P = 0.03) and percentage (P = 0.09), and insulin and HOMA-IR were associated with visceral fat area (P = 0.001) and percentage (P = 0.005). Conclusions 3T MRI can provide reliable and good quality images for quantification of visceral and subcutaneous fat by using a free software package. The results demonstrate that WC is a good predictor of visceral fat in obese adolescents and visceral fat area is associated with total cholesterol/HDL ratio, insulin and HOMA-IR. PMID:28129354

  16. Urinary epinephrine and norepinephrine interrelations with obesity, insulin, and the metabolic syndrome in Hong Kong Chinese.

    PubMed

    Lee, Z S; Critchley, J A; Tomlinson, B; Young, R P; Thomas, G N; Cockram, C S; Chan, T Y; Chan, J C

    2001-02-01

    The metabolic syndrome is characterized by a clustering of cardiovascular risk factors including type 2 diabetes mellitus, hypertension, dyslipidemia, and obesity. Elevated plasma insulin and urinary norepinephrine (noradrenaline) and reduced urinary epinephrine (adrenaline) excretion are associated with obesity in Caucasian populations. We examined the interrelationships between obesity, plasma insulin, and urinary catecholamine excretion in Chinese subjects with various components of the metabolic syndrome. A total of 577 Chinese subjects (aged 38 +/- 10 years; 68% with type 2 diabetes mellitus, hypertension, dyslipidemia, obesity, and/or albuminuria and 32% healthy subjects) were studied, all of whom had a plasma creatinine less than 150 micromol/L. The blood pressure, height, weight, waist and hip circumference, and fasting plasma glucose, insulin, lipid, and creatinine levels were measured. A 24-hour urine sample was collected for measurement of albumin and catecholamine excretion. The body mass index (BMI) and waist circumference were used as measures of general and central obesity, respectively. The insulin resistance index was estimated by the calculated product of fasting plasma insulin and glucose concentrations. Patients with an increasing number of components of the metabolic syndrome (type 2 diabetes mellitus, hypertension, dyslipidemia, obesity, and/or albuminuria) were more obese, hyperglycemic, dyslipidemic, and albuminuric and had higher blood pressure, plasma insulin, insulin resistance indices, and 24-hour urinary norepinephrine excretion but lower urinary epinephrine output (all P < .005). Increasing quintiles of BMI in the whole population or waist circumference in both sexes were associated with increasing trends for adverse lipid profiles, plasma insulin, insulin resistance indices, and urinary norepinephrine excretion but a decreasing trend for urinary epinephrine output (all P < .001). There were close associations between age, obesity

  17. Abdominal obesity validates the association between elevated alanine aminotransferase and newly diagnosed diabetes mellitus.

    PubMed

    Yueh, Chen-Yu; Yang, Yao-Hsu; Sung, Yi-Ting; Lee, Li-Wen

    2014-01-01

    To examine how elevated alanine aminotransferase (ALT) could be associated with newly diagnosed diabetes mellitus. We conducted a cross-sectional analysis on a mass health examination. The odds ratios (ORs) for diabetes mellitus and newly diagnosed diabetes mellitus were compared between people with and without abdominal obesity, together with and without elevated ALT levels. 5499 people were included in this study. Two hundred fifty two (4.6%) fulfilled the diagnosis of diabetes mellitus with 178 (3.2%) undiagnosed before. Metabolic syndrome was vigorously associated with diabetes mellitus and newly diagnosed diabetes mellitus (12.4% vs. 1.4% and 9.0% vs. 0.9%), but elevated ALT alone was not. However, coexisting with obesity, elevated ALTs were robustly associated with diabetes mellitus and newly diagnosed diabetes mellitus. For the incidence of newly diagnosed diabetes mellitus, in comparison to non-obese people with normal ALT (1.7%, OR = 1), obese people especially with elevated ALT levels had significantly higher ORs (obese with ALT ≤ 40 U/L: 4.7%, OR 1.73, 95% CI 1.08-2.77, P 0.023; ALT 41-80 U/L: 6.8%, OR 2.06, 95% CI 1.20-3.55, P 0.009; ALT 81-120 U/L: 8.8%, OR 3.07, 95% CI 1.38-6.84, P 0.006; ALT > 120 U/L: 18.2%, OR 7.44, 95% CI 3.04-18.18, P < 0.001). Abdominal obesity validates the association between elevated alanine aminotransferase and diabetes mellitus and newly diagnosed diabetes mellitus. People with abdominal obesity, especially with coexisting elevated ALT levels should be screened for undiagnosed diabetes mellitus.

  18. Castration influences intestinal microflora and induces abdominal obesity in high-fat diet-fed mice

    PubMed Central

    Harada, Naoki; Hanaoka, Ryo; Horiuchi, Hiroko; Kitakaze, Tomoya; Mitani, Takakazu; Inui, Hiroshi; Yamaji, Ryoichi

    2016-01-01

    Late-onset hypogonadism (i.e. androgen deficiency) raises the risk for abdominal obesity in men. The mechanism for this obesity is unclear. Here, we demonstrated that hypogonadism after castration caused abdominal obesity in high-fat diet (HFD)-fed, but not in standard diet (SD)-fed, C57BL/6J mice. Furthermore, the phenotype was not induced in mice treated with antibiotics that disrupt the intestinal microflora. In HFD-fed mice, castration increased feed efficiency and decreased fecal weight per food intake. Castration also induced in an increase of visceral fat mass only in the absence of antibiotics in HFD-fed mice, whereas subcutaneous fat mass was increased by castration irrespective of antibiotics. Castration reduced the expression in the mesenteric fat of both adipose triglyceride lipase and hormone-sensitive lipase in HFD-fed mice, which was not observed in the presence of antibiotics. Castration decreased thigh muscle (i.e. quadriceps and hamstrings) mass, elevated fasting blood glucose levels, and increased liver triglyceride levels in a HFD-dependent manner, whereas these changes were not observed in castrated mice treated with antibiotics. The Firmicutes/Bacteroidetes ratio and Lactobacillus species increased in the feces of HFD-fed castrated mice. These results show that androgen (e.g. testosterone) deficiency can alter the intestinal microbiome and induce abdominal obesity in a diet-dependent manner. PMID:26961573

  19. Mechanism by Which Caloric Restriction Improves Insulin Sensitivity in Sedentary Obese Adults

    PubMed Central

    Johnson, Matthew L.; Distelmaier, Klaus; Lanza, Ian R.; Irving, Brian A.; Robinson, Matthew M.; Konopka, Adam R.; Shulman, Gerald I.

    2016-01-01

    Caloric restriction (CR) improves insulin sensitivity and reduces the incidence of diabetes in obese individuals. The underlying mechanisms whereby CR improves insulin sensitivity are not clear. We evaluated the effect of 16 weeks of CR on whole-body insulin sensitivity by pancreatic clamp before and after CR in 11 obese participants (BMI = 35 kg/m2) compared with 9 matched control subjects (BMI = 34 kg/m2). Compared with the control subjects, CR increased the glucose infusion rate needed to maintain euglycemia during hyperinsulinemia, indicating enhancement of peripheral insulin sensitivity. This improvement in insulin sensitivity was not accompanied by changes in skeletal muscle mitochondrial oxidative capacity or oxidant emissions, nor were there changes in skeletal muscle ceramide, diacylglycerol, or amino acid metabolite levels. However, CR lowered insulin-stimulated thioredoxin-interacting protein (TXNIP) levels and enhanced nonoxidative glucose disposal. These results support a role for TXNIP in mediating the improvement in peripheral insulin sensitivity after CR. PMID:26324180

  20. Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance

    NASA Astrophysics Data System (ADS)

    Hotamisligil, Gokhan S.; Shargill, Narinder S.; Spiegelman, Bruce M.

    1993-01-01

    Tumor necrosis factor-α (TNF-α) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-α messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-α protein was also elevated locally and systemically. Neutralization of TNF-α in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-α in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.

  1. Influence of various carbohydrate sources on postprandial glucose, insulin and NEFA concentrations in obese cats.

    PubMed

    Mori, A; Ueda, K; Lee, P; Oda, H; Ishioka, K; Sako, T

    2016-01-01

    Carbohydrate is an important source of energy, which can significantly affect postprandial blood glucose and insulin levels in cats. In healthy animals, this is not a big concern; however, in obese and diabetic animals, this is an important detail. In the present study, the impact of four different carbohydrate sources (glucose, maltose, corn starch, and trehalose) on short-term post-prandial serum glucose, insulin, and non-esterified fatty acid (NEFA) concentrations was investigated with four obese cats. Each of the carbohydrate sources was added to a commercial wet food diet for feeding the animals. A significant difference was observed in postprandial glucose, insulin, and NEFA area under the curve (AUC) values between each carbohydrate source in obese cats. Furthermore, glucose and maltose induced the highest postprandial glucose and insulin AUC values, whereas trehalose induced the lowest postprandial glucose and insulin AUC value amongst all carbohydrate sources, respectively, in obese cats. However, trehalose has a higher risk of inducing side effects, such as diarrhea, as compared to other carbohydrate sources. As such, different carbohydrate sources appear to have a very significant impact on post-prandial glycemia and subsequent insulin requirement levels in obese cats. These results might be useful when selecting a prescription diet for obese or diabetic cats. In addition, maltose appears to be capable of inducing experimentally evoked postprandial hyperglycemia in obese cats, which may serve as a good tool for use to check the impact and effectiveness of newly developed oral hypoglycemic drugs or supplements for cats in future experiments.

  2. The role of uric acid in the insulin resistance in children and adolescents with obesity

    PubMed Central

    de Miranda, Josiane Aparecida; Almeida, Guilherme Gomide; Martins, Raissa Isabelle Leão; Cunha, Mariana Botrel; Belo, Vanessa Almeida; dos Santos, José Eduardo Tanus; Mourão-Júnior, Carlos Alberto; Lanna, Carla Márcia Moreira

    2015-01-01

    Objective: To investigate the association between serum uric acid levels and insulin resistance in children and adolescents with obesity. Methods: Cross-sectional study with 245 children and adolescents (134 obese and 111 controls), aged 8-18 years. The anthropometric variables (weight, height and waist circumference), blood pressure and biochemical parameters were collected. The clinical characteristics of the groups were analyzed by t-test or chi-square test. To evaluate the association between uric acid levels and insulin resistance the Pearson's test and logistic regression were applied. Results: The prevalence of insulin resistance was 26.9%. The anthropometric variables, systolic and diastolic blood pressure and biochemical variables were significantly higher in the obese group (p<0.001), except for the high-density-lipoprotein cholesterol. There was a positive and significant correlation between anthropometric variables and uric acid with HOMA-IR in the obese and in the control groups, which was higher in the obese group and in the total sample. The logistic regression model that included age, gender and obesity, showed an odds ratio of uric acid as a variable associated with insulin resistance of 1.91 (95%CI 1.40-2.62; p<−0.001). Conclusions: The increase in serum uric acid showed a positive statistical correlation with insulin resistance and it is associated with and increased risk of insulin resistance in obese children and adolescents. PMID:26300523

  3. Effects of high-frequency current therapy on abdominal obesity in young women: a randomized controlled trial

    PubMed Central

    Kim, Jin-seop; Oh, Duck-won

    2015-01-01

    [Purpose] The aim of this study was to determine the effects of high-frequency current therapy on the abdominal obesity levels of young women. [Subjects] Twenty-two women with abdominal obesity were randomly allocated to either an experimental group (n1 = 10) or a control group (n2 = 12). [Methods] The experimental group subjects received high-frequency current therapy for the abdominal region 3 times per week for 6 weeks (a total of 18 sessions). Outcome measures were waist circumference, body mass index, and body composition data (abdominal obesity rate, subcutaneous fat mass, and body fat percentage). [Results] Significant main effects of time in the waist circumference, abdominal obesity rate, subcutaneous fat mass, and body fat percentage were found. Significant time-by-group interactions were found for waist circumference, abdominal obesity rate, subcutaneous fat mass, and body fat percentage. [Conclusion] The use of the high-frequency current therapy may be beneficial for reducing the levels of abdominal obesity in young women. PMID:25642031

  4. Secular trends in the prevalence of general and abdominal obesity among Chinese adults, 1993-2009.

    PubMed

    Xi, B; Liang, Y; He, T; Reilly, K H; Hu, Y; Wang, Q; Yan, Y; Mi, J

    2012-03-01

    The objective of this study is to examine the trends in body mass index (BMI), waist circumference (WC) and prevalence of overweight (BMI 25-27.49 kg m(-2) ), general obesity (BMI ≥ 27.5 kg m(-2) ) and abdominal obesity (WC ≥ 90 cm for men and ≥80 cm for women) among Chinese adults from 1993 to 2009. Data were obtained from the China Health and Nutrition Survey, which was conducted from 1993 to 2009 and included a total of 52,621 Chinese adults. During the period of 1993-2009, mean BMI values increased by 1.6 kg m(-2) among men and 0.8 kg m(-2) among women; mean WC values increased by 7.0 cm among men and 4.7 cm among women. The prevalence of overweight increased from 8.0 to 17.1% among men (P < 0.001) and from 10.7 to 14.4% among women (P < 0.001); the prevalence of general obesity increased from 2.9 to 11.4% among men (P < 0.001) and from 5.0 to 10.1% among women (P < 0.001); the prevalence of abdominal obesity increased from 8.5 to 27.8% among men (P < 0.001) and from 27.8 to 45.9% among women (P < 0.001). Similar significant trends were observed in nearly all age groups and regions for both men and women. The prevalence of overweight, general obesity and abdominal obesity among Chinese adults has increased greatly during the past 17 years.

  5. Dietary supplementation with short-chain fructo-oligosaccharides improves insulin sensitivity in obese horses.

    PubMed

    Respondek, F; Myers, K; Smith, T L; Wagner, A; Geor, R J

    2011-01-01

    Obesity and insulin resistance are risk factors for laminitis in horses and ponies, and diet can play an important role in modulating these risk factors. Dietary supplementation with prebiotic fibers, such as short-chain fructo-oligosaccharides (scFOS), has resulted in improvement of insulin sensitivity in obese dogs and rodents. Thus, we hypothesized that scFOS may reduce insulin resistance in obese horses and designed a study to evaluate the effect of dietary supplementation with scFOS on insulin sensitivity. Eight mature Arabian geldings (BW = 523.0 ± 56.5 kg) with an average BCS of 8 were included in a crossover study. In each period, 4 horses were provided 45 g/d per horse of maltodextrin (control) and 4 horses received the same amount of scFOS for 6 wk, with a 3-wk washout between periods. Resting plasma concentrations of glucose, insulin, triglycerides, and leptin were measured. Minimal model analysis of a frequently sampled intravenous glucose tolerance test was used to evaluate insulin sensitivity, glucose effectiveness, acute insulin response to glucose, and disposition index. Without affecting BW and BCS, dietary supplementation with scFOS increased (P < 0.05) insulin sensitivity and reduced (P < 0.05) acute insulin response to glucose in comparison with maltodextrin but did not alter (P > 0.05) glucose effectiveness and disposition index. Resting serum insulin concentration also was reduced (P < 0.05) by scFOS supplementation but not by maltodextrin (P > 0.05). There was no effect (P > 0.05) of scFOS supplementation on plasma glucose or serum triglyceride and leptin concentrations. This study demonstrated that scFOS can moderately improve insulin sensitivity of obese horses, a finding that has potential relevance to the dietary management of obese, insulin-resistant horses at increased risk for laminitis.

  6. [THE INFLUENCE OF ABDOMINAL OBESITY ON LEFT VENTRICULAR MYOCARDIALREMODELING IN PATIENTS WITH ARTERIAL HYPERTENSION].

    PubMed

    Poteklzin, N P; Sarkisov, K A; Orlov, F A; Alatortseva, I A; Starovoitova, L M; Drozdova, I N

    2015-01-01

    The obesity dependence of selected clinical and instrumental characteristics of 10 male patients with arterial hypertension (AH) was evaluated Group I included 79 patients with grade II hypertensive disease (HD), normal body weight and waist circumference. Group 2 comprised 61 patients with grade II HD and abdominal obesity. Patients of both groups showed high frequency of left ventricular (LV) hypertrophy (59.2 and 73.8% respectively). Concentric LV hypertrophy prevailed in group I and eccentric hypertrophy in group 2. 24 hr ECG monitoring showed that signs of relative coronary insufficiency were recorded more frequently in group 2 and cardiac rhythm disturbances in group I.

  7. B Lymphocytes in obesity related adipose tissue inflammation and insulin resistance

    PubMed Central

    Winer, Daniel A.; Winer, Shawn; Chng, Melissa H. Y.; Shen, Lei; Engleman, Edgar G.

    2013-01-01

    Obesity related insulin resistance is a chronic inflammatory condition that often gives rise to type 2 diabetes (T2D). Much evidence supports a role for pro-inflammatory T cells and macrophages in promoting local inflammation in tissues such as visceral adipose tissue (VAT) leading to insulin resistance. More recently, B cells have emerged as an additional critical player in orchestrating these processes. B cells infiltrate VAT and display functional and phenotypic changes in response to diet induced obesity. B cells contribute to insulin resistance by presenting antigens to T cells, secreting inflammatory cytokines and producing pathogenic antibodies. B cell manipulation represents a novel approach to the treatment of obesity related insulin resistance and potentially to the prevention of T2D. This review summarizes the roles of B cells in governing VAT inflammation and the mechanisms by which these cells contribute to altered glucose homeostasis in insulin resistance. PMID:24127133

  8. Hepatocyte TRAF3 promotes insulin resistance and type 2 diabetes in mice with obesity

    PubMed Central

    Chen, Zheng; Canet, Mark J.; Sheng, Liang; Jiang, Lin; Xiong, Yi; Yin, Lei; Rui, Liangyou

    2015-01-01

    Objective Metabolic inflammation is believed to promote insulin resistance and type 2 diabetes progression in obesity. TRAF3, a cytoplasmic signaling protein, has been known to mediate/modulate cytokine signaling in immune cells. The goal is to define the metabolic function of hepatic TRAF3 in the setting of obesity. Methods Hepatocyte-specific TRAF3 knockout mice were generated using the loxp/albumin-cre system. Liver TRAF3 was deleted in adult obese mice via Cre adenoviral infection. Both high fat diet-induced and genetic obesity were examined. TRAF3 levels and insulin signaling were measured by immunoblotting. Insulin sensitivity, hepatic glucose production, and glucose metabolism were examined by glucose, insulin, and pyruvate tolerance tests. Hepatic steatosis was examined by Oil red O staining of liver sections and measuring liver triacylglycerol levels. Results Liver TRAF3 levels were lower in the fasted states in normal mice, and were aberrantly higher in obese mice and in mice with streptozotocin-induced hyperglycemia. Glucose directly increased TRAF3 levels in primary hepatocytes. Hepatocyte-specific deletion of TRAF3 decreased hyperinsulinemia, insulin resistance, glucose intolerance, and hepatic steatosis in mice with either high fat diet-induced obesity or genetic obesity (ob/ob); conversely, in lean mice, adenovirus-mediated overexpression of TRAF3 in the liver induced hyperinsulinemia, insulin resistance, and glucose intolerance. Deletion of TRAF3 enhanced the ability of insulin to stimulate phosphorylation of Akt in hepatocytes, whereas overexpression of TRAF3 suppressed insulin signaling. Conclusions Glucose increases the levels of hepatic TRAF3. TRAF3 in turn promotes hyperglycemia through increasing hepatic glucose production, thus forming a glucose-TRAF3 reinforcement loop in the liver. This positive feedback loop may drive the progression of type 2 diabetes and nonalcoholic fatty liver disease in obesity. PMID:26909311

  9. Developmental programming of obesity and insulin resistance: does mitochondrial dysfunction in oocytes play a role?

    PubMed

    Turner, Nigel; Robker, Rebecca L

    2015-01-01

    Insulin resistance is a key defect associated with obesity, type 2 diabetes and other metabolic diseases. While a number of factors have been suggested to cause defects in insulin action, there is a very strong association between inappropriate lipid deposition in insulin target tissues and the development of insulin resistance. In recent times, a large number of studies have reported changes in markers of mitochondrial metabolism in insulin-resistant individuals, leading to the theory that defects in mitochondrial substrate oxidation are responsible for the buildup of lipid intermediates and the development of insulin resistance. The primary support for the mitochondrial theory of insulin resistance comes from studies in skeletal muscle; however, there is recent evidence in murine models that mitochondrial dysfunction in oocytes may also play a role. Oocytes from obese or insulin-resistant mice have been shown to exhibit abnormalities in many different mitochondrial parameters, including mitochondrial morphology and membrane potential. Here we review the findings regarding the link between mitochondrial dysfunction and insulin resistance, and propose that abnormalities in mitochondrial metabolism in oocytes may predispose to the development of obesity and insulin resistance and thus contribute to the inter-generational programming of metabolic disease.

  10. Zinc, iron and vitamins A, C and e are associated with obesity, inflammation, lipid profile and insulin resistance in Mexican school-aged children.

    PubMed

    García, Olga Patricia; Ronquillo, Dolores; del Carmen Caamaño, María; Martínez, Guadalupe; Camacho, Mariela; López, Viridiana; Rosado, Jorge L

    2013-12-10

    The objective of this cross-sectional study was to evaluate the relationship between micronutrient status and obesity, lipids, insulin resistance and chronic inflammation in children. Weight, height, waist circumference and body composition (dual-energy X-ray absorptiometry (DEXA)) were determined in 197 school-aged children. Lipids, glucose, insulin, C-reactive protein (CRP), zinc, iron and vitamins A, C and E were analyzed in blood. Vitamin C and vitamin E:lipids were negatively associated with Body Mass Index (BMI), waist-to-height ratio (WHR) and body and abdominal fat (p < 0.05). Vitamin A was positively associated with BMI, BMI-for-age, WHR and abdominal fat (p < 0.05). Iron and vitamin E:lipids were negatively associated with insulin (p < 0.05). Vitamins A, C and E and iron were negatively associated with CRP (p < 0.05). Interaction analysis showed that children who were overweight and obese who also had low concentrations of vitamin A had higher CRP and lower triglycerides (p < 0.1), children with low vitamin E had significantly lower glucose and triglycerides (p < 0.1) and higher low-density lipoprotein (LDL) concentrations (p < 0.05), and children with low zinc concentrations had higher insulin resistance compared with children with adequate weight (p < 0.05). In conclusion, low vitamin C concentration and vitamin E:lipids were associated with obesity. Furthermore, low concentrations of zinc, vitamins A and E in children who were overweight and obese were associated with lipids, inflammation and insulin resistance.

  11. Oxidation of nonplasma fatty acids during exercise is increased in women with abdominal obesity.

    PubMed

    Horowitz, J F; Klein, S

    2000-12-01

    We evaluated plasma fatty acid availability and plasma and whole body fatty acid oxidation during exercise in five lean and five abdominally obese women (body mass index = 21 +/- 1 vs. 38 +/- 1 kg/m(2)), who were matched on aerobic fitness, to test the hypothesis that obesity alters the relative contribution of plasma and nonplasma fatty acids to total energy production during exercise. Subjects exercised on a recumbent cycle ergometer for 90 min at 54% of their peak oxygen consumption. Stable isotope tracer methods ([(13)C]palmitate) were used to measure fatty acid rate of appearance in plasma and the rate of plasma fatty acid oxidation, and indirect calorimetry was used to measure whole body substrate oxidation. During exercise, palmitate rate of appearance increased progressively and was similar in obese and lean groups between 60 and 90 min of exercise [3.9 +/- 0.4 vs. 4.0 +/- 0.3 micromol. kg fat free mass (FFM)(-1). min(-1)]. The rate of plasma fatty acid oxidation was also similar in obese and lean subjects (12.8 +/- 1.7 vs. 14.5 +/- 1.8 micromol. kg FFM(-1). min(-1); P = not significant). However, whole body fatty acid oxidation during exercise was 25% greater in obese than in lean subjects (21.9 +/- 1.2 vs. 17.5 +/- 1.6 micromol. kg FFM(-1). min(-1); P < 0.05). These results demonstrate that, although plasma fatty acid availability and oxidation are similar during exercise in lean and obese women, women with abdominal obesity use more fat as a fuel by oxidizing more nonplasma fatty acids.

  12. Adipogenesis and insulin sensitivity in obesity are regulated by retinoid-related orphan receptor gamma

    PubMed Central

    Meissburger, Bettina; Ukropec, Jozef; Roeder, Eva; Beaton, Nigel; Geiger, Matthias; Teupser, Daniel; Civan, Burcak; Langhans, Wolfgang; Nawroth, Peter P; Gasperikova, Daniela; Rudofsky, Gottfried; Wolfrum, Christian

    2011-01-01

    Obesity is a well-known risk factor for the development of secondary complications such as type 2 diabetes. However, only a part of the obese population develops secondary metabolic disorders. Here, we identify the transcription factor retinoid-related orphan receptor gamma (RORγ) as a negative regulator of adipocyte differentiation through expression of its newly identified target gene matrix metalloproteinase 3. In vivo differentiation of adipocyte progenitor cells from Rorγ-deficient mice is enhanced and obese Rorγ−/− mice show decreased adipocyte sizes. These small adipocytes are highly insulin sensitive, leading to an improved control of circulating free fatty acids. Ultimately, Rorγ−/− mice are protected from hyperglycemia and insulin resistance in the state of obesity. In adipose stromal-vascular fraction from obese human subjects, Rorγ expression is correlated with adipocyte size and negatively correlated with adipogenesis and insulin sensitivity. Taken together, our findings identify RORγ as a factor, which controls adipogenesis as well as adipocyte size and modulates insulin sensitivity in obesity. RORγ might therefore serve as a novel pharmaceutical target to treat obesity-associated insulin resistance. PMID:21853531

  13. Myoinositol and D-Chiro Inositol in Improving Insulin Resistance in Obese Male Children: Preliminary Data

    PubMed Central

    Andreassi, Alice; Salvioni, Michela; Pelliccione, Fiore; Mantellassi, Gianna; Banderali, Giuseppe

    2016-01-01

    Myoinositol and D-chiro inositol, which are inositol isomers, have been shown to possess insulin-mimetic properties and to improve insulin resistance, especially in women with polycystic ovary syndrome. However, it has not been determined if this relationship exists also in children. Based on these previous findings, we hypothesized that inositol could be effective in improving insulin sensitivity in children with insulin resistance. To evaluate this hypothesis, we administered both inositol formulations before carrying out an oral glucose tolerance test (OGTT) in a group of obese insulin-resistant male children with high basal insulin levels and compared the values obtained with an OGTT previously conducted without inositol, in the same group, with unchanged BMI. Our results confirm that myoinositol and D-chiro inositol acutely reduce insulin increase after glucose intake mainly in children with high basal insulin level. PMID:27882052

  14. Reversal of diet-induced obesity and insulin resistance by inducible genetic ablation of GRK2

    PubMed Central

    Vila-Bedmar, Rocio; Cruces-Sande, Marta; Lucas, Elisa; Willemen, Hanneke L.D.M.; Heijnen, Cobi J.; Kavelaars, Annemieke; Mayor, Federico; Murga, Cristina

    2015-01-01

    Insulin resistance is a common feature of obesity and predisposes individuals to various prevalent pathological conditions. G protein-coupled receptor kinase 2 (GRK2) integrates several signal transduction pathways and is emerging as a physiologically relevant inhibitor of insulin signaling. GRK2 abundanceis increased in humans with metabolic syndrome and in different murine models of insulin resistance. To support GRK2 as a potential drug target in type 2 diabetes and obesity, we investigated whether lowering GRK2 abundance reversed an ongoing systemic insulin-resistant phenotype, using a mouse model of tamoxifen-induced GRK2 ablation after high fat diet-dependent obesity and insulin resistance. Tamoxifen-triggered GRK2 deletion impeded further body weight gain, normalized fa sting glycemia, improved glucose tolerance and was associated with preserved insulin sensitivity in skeletal muscle and liver, thereby maintaining whole body glucose homeostasis. Moreover, when continued to be fed a high fat diet, these animals displayed reduced fat mass and smaller adipocytes, were resistant to the development of liver steatosis, and showed reduced expression of pro-inflammatory markers in the liver. Our results indicate that GRK2 acts as a hub to control metabolic functions in different tissues, which is key to controlling insulin resistance development in vivo. These data suggest that inhibiting GRK2 could reverse an established insulin-resistant and obese phenotype, thereby putting forward this enzyme as a potential therapeutic target linking glucose homeostasis and regulation of adiposity. PMID:26198359

  15. Indices of insulin secretion during a liquid mixed-meal test in obese youth with diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To compare indices of insulin secretion, insulin sensitivity (IS),and oral disposition index (oDI) during the liquid mixed-meal test in obese youth with clinically diagnosed type 2 diabetes mellitus (T2DM) and negative autoantibodies (Ab-) versus those with T2DM and positive autoantibodies (Ab+) to ...

  16. Estimate of a predictive cut-off value for serum 25-hydroxyvitamin D reflecting abdominal obesity in Korean adolescents.

    PubMed

    Nam, Ga Eun; Kim, Do Hoon; Cho, Kyung Hwan; Park, Yong Gyu; Han, Kyung Do; Choi, Youn Seon; Kim, Seon Mee; Ko, Byung Joon; Kim, Yang Hyun; Lee, Kyung Shik

    2012-06-01

    Vitamin D deficiency is a serious global issue. Although the serum 25-hydroxyvitamin D [25(OH)D] test is generally the most accurate way to assess vitamin D levels, the optimal range of 25(OH)D has yet to be established. Moreover, the optimal level may vary according to race, region, and age. Suboptimal vitamin D status is associated with obesity and metabolic syndrome, which are the major risk factors for cardiovascular disorders; however, these relationships in children and adolescents have yet to be clearly determined. Therefore, we identified the best predictive cut-off value for reflecting abdominal obesity and, based on this value, we investigated the relationship between suboptimal 25(OH)D status and the risk for having abdominal obesity, being overweight or obese, and having metabolic syndrome in Korean adolescents. We performed a cross-sectional analysis of 713 Korean adolescents, between 12-19 years of age, and used data collected from the 2008 Korea National Health and Nutrition Examination Survey (KNHANES). Receiver operation characteristic curve analysis was used to identify the cut-off value that reflected abdominal obesity. The cut-off value of serum 25(OH)D that reflected abdominal obesity in Korean adolescents was 17.6 ng/mL. After making adjustments for gender, age, and regular physical exercise, the group that had lower levels of serum 25(OH)D compared to the cut-off value had a significantly higher risk for abdominal obesity, obesity, and metabolic syndrome than the group with 25(OH)D levels higher than the cut-off value. Suboptimal vitamin D status based on this value is associated with increased risk for abdominal obesity, obesity, and metabolic syndrome among Korean adolescents.

  17. Resistance exercise increase lean body mass and improves basal and hepatic insulin sensitivity in obese adolescents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little is known about the metabolic effects of resistance exercise, for instance, weight lifting. We studied whether a resistance exercise program improves insulin sensitivity and glucose metabolism in sedentary obese adolescents. Elevn obese subjects (15.7 +/- 0.4 year; 35.4 +/- 0.8 kg/m2; 41.3 +/-...

  18. Adipokines, ghrelin and obesity-associated insulin resistance in nondiabetic patients with acute coronary syndrome.

    PubMed

    Barazzoni, Rocco; Aleksova, Aneta; Armellini, Ilaria; Cattin, Maria Rosa; Zanetti, Michela; Carriere, Cosimo; Giacca, Mauro; Dore, Franca; Guarnieri, Gianfranco; Sinagra, Gianfranco

    2012-12-01

    Altered glucose metabolism negatively modulates outcome in acute coronary syndromes (ACS). Insulin resistance is commonly associated with increasing BMI in the general population and these associations may involve obesity-related changes in circulating ghrelin and adipokines. We aimed at investigating interactions between BMI, insulin resistance and ACS and their associations with plasma ghrelin and adipokine concentrations. Homeostasis model assessment of insulin resistance (HOMA(IR))-insulin resistance index, plasma adiponectin, leptin, total (T-Ghrelin), acylated (Acyl-Ghrelin), and desacylated ghrelin (Desacyl-Ghrelin) were measured in 60 nondiabetic ACS patients and 44 subjects without ACS matched for age, sex, and BMI. Compared with non-ACS, ACS patients had similar HOMA(IR) and plasma adipokines, but lower T- and Desacyl-Ghrelin and higher Acyl-Ghrelin. Obesity (BMI > 30) was associated with higher HOMA(IR), lower adiponectin, and higher leptin (P < 0.05) similarly in ACS and non-ACS subjects. In ACS (n = 60) HOMA(IR) remained associated negatively with adiponectin and positively with leptin independently of BMI and c-reactive protein (CRP) (P < 0.05). On the other hand, low T- and Desacyl-Ghrelin with high Acyl-Ghrelin characterized both obese and non-obese ACS patients and were not associated with HOMA(IR). In conclusion, in ACS patients, obesity and obesity-related changes in plasma leptin and adiponectin are associated with and likely contribute to negatively modulate insulin resistance. ACS per se does not however enhance the negative impact of obesity on insulin sensitivity. High acylated and low desacylated ghrelin characterize ACS patients independently of obesity, but are not associated with insulin sensitivity.

  19. Abdominal adiposity, insulin and bone quality in young male rats fed a high-fat diet containing soybean or canola oil

    PubMed Central

    da Costa, Carlos Alberto Soares; Carlos, Aluana Santana; de Sousa dos Santos, Aline; Monteiro, Alexandra Maria Vieira; de Moura, Egberto Gaspar; Nascimento-Saba, Celly Cristina Alves

    2011-01-01

    OBJECTIVES: A low ratio of omega-6/omega-3 polyunsaturated fatty acids is associated with healthy bone properties. However, fatty diets can induce obesity. Our objective was to evaluate intra-abdominal adiposity, insulin, and bone growth in rats fed a high-fat diet containing low ratios of omega-6/omega-3 provided in canola oil. METHODS: After weaning, rats were grouped and fed either a control diet (7S), a high-fat diet containing soybean oil (19S) or a high-fat diet of canola oil (19C) until they were 60 days old. Differences were considered to be significant if p<0.05. RESULTS: After 60 days, the 19S and 19C groups showed more energy intake, body density growth and intra-abdominal fat mass. However, the 19S group had a higher area (200%) and a lower number (44%) of adipocytes, while the 7S and 19C groups did not differ. The serum concentrations of glucose and insulin and the insulin resistance index were significantly increased in the 19C group (15%, 56%, and 78%, respectively) compared to the 7S group. Bone measurements of the 19S and 19C groups showed a higher femur mass (25%) and a higher lumbar vertebrae mass (11%) and length (5%). Computed tomography analysis revealed more radiodensity in the proximal femoral epiphysis and lumbar vertebrae of 19C group compared to the 7S and 19S groups. CONCLUSIONS: Our results suggest that the amount and source of fat used in the diet after weaning increase body growth and fat depots and affect insulin resistance and, consequently, bone health. PMID:22012056

  20. Abdominal Obesity and Lung Cancer Risk: Systematic Review and Meta-Analysis of Prospective Studies

    PubMed Central

    Hidayat, Khemayanto; Du, Xuan; Chen, Guochong; Shi, Minhua; Shi, Bimin

    2016-01-01

    Several meta-analyses of observational studies have been performed to examine the association between general obesity, as measured by body mass index (BMI), and lung cancer. These meta-analyses suggest an inverse relation between high BMI and this cancer. In contrast to general obesity, abdominal obesity appears to play a role in the development of lung cancer. However, the association between abdominal obesity (as measured by waist circumference (WC) (BMI adjusted) and waist to hip ratio (WHR)) and lung cancer is not fully understood due to sparse available evidence regarding this association. PubMed and Web of Science databases were searched for studies assessing the association between abdominal obesity and lung cancer up to October 2016. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with a random-effects model. Six prospective cohort studies with 5827 lung cancer cases among 831,535 participants were included in our meta-analysis. Each 10 cm increase in WC and 0.1 unit increase in WHR were associated with 10% (RR 1.10; 95% CI 1.04, 1.17; I2 = 27.7%, p-heterogeneity = 0.198) and 5% (RR 1.05; 95% CI 1.00, 1.11; I2 = 25.2%, p-heterogeneity = 0.211) greater risks of lung cancer, respectively. According to smoking status, greater WHR was only positively associated with lung cancer among former smokers (RR 1.11; 95% CI 1.00, 1.23). In contrast, greater WC was associated with increased lung cancer risk among never smokers (RR 1.11; 95% CI 1.00, 1.23), former smokers (RR 1.12; 95% CI 1.03, 1.22) and current smokers (RR 1.16; 95% CI 1.08, 1.25). The summary RRs for highest versus lowest categories of WC and WHR were 1.32 (95% CI 1.13, 1.54; I2 = 18.2%, p-heterogeneity = 0.281) and 1.10 (95% CI 1.00, 1.23; I2 = 24.2%, p-heterogeneity = 0.211), respectively. In summary, abdominal obesity may play an important role in the development of lung cancer. PMID:27983672

  1. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity.

    PubMed

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-12-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications.

  2. Insulin receptor phosphorylation, insulin receptor substrate-1 phosphorylation, and phosphatidylinositol 3-kinase activity are decreased in intact skeletal muscle strips from obese subjects.

    PubMed Central

    Goodyear, L J; Giorgino, F; Sherman, L A; Carey, J; Smith, R J; Dohm, G L

    1995-01-01

    To determine whether the impaired insulin-stimulated glucose uptake in obese individuals is associated with altered insulin receptor signaling, we measured both glucose uptake and early steps in the insulin action pathway in intact strips of human skeletal muscle. Biopsies of rectus abdominus muscle were taken from eight obese and eight control subjects undergoing elective surgery (body mass index 52.9 +/- 3.6 vs 25.7 +/- 0.9). Insulin-stimulated 2-deoxyglucose uptake was 53% lower in muscle strips from obese subjects. Additional muscle strips were incubated in the basal state or with 10(-7) M insulin for 2, 15, or 30 min. In the lean subjects, tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 (IRS-1), measured by immunoblotting with anti-phosphotyrosine antibodies, was significantly increased by insulin at all time points. In the skeletal muscle from the obese subjects, insulin was less effective in stimulating tyrosine phosphorylation (maximum receptor and IRS-1 phosphorylation decreased by 35 and 38%, respectively). Insulin stimulation of IRS-1 immunoprecipitable phosphatidylinositol 3-kinase (PI 3-kinase) activity also was markedly lower in obese subjects compared with controls (10- vs 35-fold above basal, respectively). In addition, the obese subjects had a lower abundance of the insulin receptor, IRS-1, and the p85 subunit of PI 3-kinase (55, 54, and 64% of nonobese, respectively). We conclude that impaired insulin-stimulated glucose uptake in skeletal muscle from severely obese subjects is accompanied by a deficiency in insulin receptor signaling, which may contribute to decreased insulin action. Images PMID:7537758

  3. Insulin resistance in Mexican Americans--a precursor to obesity and diabetes?

    PubMed

    McCarty, M F

    1993-10-01

    Mexican Americans appear to have a strong genetic predisposition to insulin resistance, android obesity, and type II diabetes, apparently as a function of Native American genetic heritage. Theoretical considerations suggest that insulin resistance may be a primary factor that plays a causative role in the induction of both obesity and diabetes. Measures which promote optimal insulin sensitivity--chromium picolinate, brewer's yeast, soluble fiber supplements, metformin, very-low-fat diet, exercise training--may have value for preventing, treating, or retarding the onset of obesity and diabetes, and merit clinical evaluation in this regard. Correction of insulin resistance may also lessen cardiovascular risk, in part by reducing LDL cholesterol and improving risk factors associated with Syndrome X. These comments are likely to be valid for other Native American groups at high risk for diabetes.

  4. Ecscr regulates insulin sensitivity and predisposition to obesity by modulating endothelial cell functions.

    PubMed

    Akakabe, Yoshiki; Koide, Masahiro; Kitamura, Youhei; Matsuo, Kiyonari; Ueyama, Tomomi; Matoba, Satoaki; Yamada, Hiroyuki; Miyata, Keishi; Oike, Yuichi; Ikeda, Koji

    2013-01-01

    Insulin resistance is closely associated with obesity and is one of the earliest symptoms of type-2 diabetes. Endothelial cells are involved in the pathogenesis of insulin resistance through their role in insulin delivery and adipose tissue angiogenesis. Here we show that Ecscr (endothelial cell surface expressed chemotaxis and apoptosis regulator; also known as ARIA), the transmembrane protein that regulates endothelial cell signalling, is highly expressed in white and brown adipose tissues, and regulates energy metabolism and glucose homeostasis by modulating endothelial cell functions. Ecscr-deficient mice fed a normal chow show improved glucose tolerance and enhanced insulin sensitivity. We demonstrate that Ecscr deletion enhances the insulin-mediated Akt/endothelial nitric oxide synthase activation in endothelial cells, which increases insulin delivery into the skeletal muscle. Ecscr deletion also protects mice on a high-fat diet from obesity and obesity-related metabolic disorders by enhancing adipose tissue angiogenesis. Conversely, targeted activation of Ecscr in endothelial cells impairs glucose tolerance and predisposes mice to diet-induced obesity. Our results suggest that the inactivation of Ecscr enhances insulin sensitivity and may represent a new therapeutic strategy for treating metabolic syndrome.

  5. Baicalin against obesity and insulin resistance through activation of AKT/AS160/GLUT4 pathway.

    PubMed

    Fang, Penghua; Yu, Mei; Zhang, Lei; Wan, Dan; Shi, Mingyi; Zhu, Yan; Bo, Ping; Zhang, Zhenwen

    2017-03-27

    Obesity may cause several metabolic complications, including insulin resistance and type 2 diabetes mellitus. Despite great advances in medicine, people still keep exploring novel and effective drugs for treatment of obesity and insulin resistance. The aim of this study was to survey if baicalin might ameliorate obesity-induced insulin resistance and to explore its signal mechanisms in skeletal muscles of mice. Diet-induced obese (DIO) mice were given 50 mg/kg baicalin intraperitoneally (i.p.) once a day for 21 days, and C2C12 myotubes were treated with 100, 200, 400 μM baicalin for 12 h in this study. Then insulin resistance indexes and insulin signal protein levels in skeletal muscles were examined. We discovered that administration of baicalin decreased food intake, body weight, HOMA-IR and NT-PGC-1α levels, but enhanced GLUT4, PGC-1α, pP38MAPK, pAKT and pAS160 contents, as well as GLUT4 mRNA, PGC-1α mRNA, PPARγ mRNA, GLUT1 mRNA expression in skeletal muscles of obese mice and myotubes of C2C12 cells, and reversed high fat diet-induced glucose and insulin intolerance, hyperglycemia and insulin resistance in the mice. These results suggest that baicalin is a powerful and promising agent for treatment of obesity and insulin resistance via Akt/AS160/GLUT4 and P38MAPK/PGC1α/GLUT4 pathway.

  6. Is beer consumption related to measures of abdominal and general obesity? A systematic review and meta-analysis.

    PubMed

    Bendsen, Nathalie T; Christensen, Robin; Bartels, Else M; Kok, Frans J; Sierksma, Aafje; Raben, Anne; Astrup, Arne

    2013-02-01

    A systematic review was conducted to assess the evidence linking beer consumption to abdominal and general obesity. Following a systematic search strategy, 35 eligible observational studies and 12 experimental studies were identified. Regarding abdominal obesity, most observational data pointed towards a positive association or no association between beer intake and waist circumference or waist-to-hip ratio in men, whereas results for women were inconsistent. Data from a subset of studies indicated that beer intake > 500 mL/day may be positively associated with abdominal obesity. Regarding general obesity, most observational studies pointed towards an inverse association or no association between beer intake and body weight in women and a positive association or no association in men. Data from six experimental studies in men, in which alcoholic beer was compared with low-alcoholic beer, suggested that consumption of alcoholic beer (for 21-126 days) results in weight gain (0.73 kg; P < 0.0001), but data from four studies comparing intake of alcoholic beer with intake of no alcohol did not support this finding. Generally, experimental studies had low-quality data. In conclusion, the available data provide inadequate scientific evidence to assess whether beer intake at moderate levels (<500 mL/day) is associated with general or abdominal obesity. Higher intake, however, may be positively associated with abdominal obesity.

  7. An Immunomodulatory Device Improves Insulin Resistance in Obese Porcine Model of Metabolic Syndrome

    PubMed Central

    Westover, Angela J.

    2016-01-01

    Obesity is associated with tissue inflammation which is a crucial etiology of insulin resistance. This inflammation centers around circulating monocytes which form proinflammatory adipose tissue macrophages (ATM). Specific approaches targeting monocytes/ATM may improve insulin resistance without the adverse side effects of generalized immunosuppression. In this regard, a biomimetic membrane leukocyte processing device, called the selective cytopheretic device (SCD), was evaluated in an Ossabaw miniature swine model of insulin resistance with metabolic syndrome. Treatment with the SCD in this porcine model demonstrated a decline in circulating neutrophil activation parameters and monocyte counts. These changes were associated with improvements in insulin resistance as determined with intravenous glucose tolerance testing. These improvements were also reflected in lowering of homeostatic model assessment- (HOMA-) insulin resistant (IR) scores for up to 2 weeks after SCD therapy. These results allow for the planning of first-in-man studies in obese type 2 diabetic patients. PMID:27819007

  8. Diet-induced obesity induces endoplasmic reticulum stress and insulin resistance in the amygdala of rats☆

    PubMed Central

    Castro, Gisele; C. Areias, Maria Fernanda; Weissmann, Lais; Quaresma, Paula G.F.; Katashima, Carlos K.; Saad, Mario J.A.; Prada, Patricia O.

    2013-01-01

    Insulin acts in the hypothalamus, decreasing food intake (FI) by the IR/PI3K/Akt pathway. This pathway is impaired in obese animals and endoplasmic reticulum (ER) stress and low-grade inflammation are possible mechanisms involved in this impairment. Here, we highlighted the amygdala as an important brain region for FI regulation in response to insulin. This regulation was dependent on PI3K/AKT pathway similar to the hypothalamus. Insulin was able to decrease neuropeptide Y (NPY) and increase oxytocin mRNA levels in the amygdala via PI3K, which may contribute to hypophagia. Additionally, obese rats did not reduce FI in response to insulin and AKT phosphorylation was decreased in the amygdala, suggesting insulin resistance. Insulin resistance was associated with ER stress and low-grade inflammation in this brain region. The inhibition of ER stress with PBA reverses insulin action/signaling, decreases NPY and increases oxytocin mRNA levels in the amygdala from obese rats, suggesting that ER stress is probably one of the mechanisms that induce insulin resistance in the amygdala. PMID:24251109

  9. Normocaloric Diet Restores Weight Gain and Insulin Sensitivity in Obese Mice

    PubMed Central

    Lombardo, Giovanni Enrico; Arcidiacono, Biagio; De Rose, Roberta Francesca; Lepore, Saverio Massimo; Costa, Nicola; Montalcini, Tiziana; Brunetti, Antonio; Russo, Diego; De Sarro, Giovambattista; Celano, Marilena

    2016-01-01

    An increased incidence of obesity is registered worldwide, and its association with insulin resistance and type 2 diabetes is closely related with increased morbidity and mortality for cardiovascular diseases. A major clinical problem in the management of obesity is the non-adherence or low adherence of patients to a hypocaloric dietetic restriction. In this study, we evaluated in obese mice the effects of shifting from high-calorie foods to normal diet on insulin sensitivity. Male C57BL/6JOlaHsd mice (n = 20) were fed with high fat diet (HFD) for a 24-week period. Afterward, body weight, energy, and food intake were measured in all animals, together with parameters of insulin sensitivity by homeostatic model assessment of insulin resistance and plasma glucose levels in response to insulin administration. Moreover, in half of these mice, Glut4 mRNA levels were measured in muscle at the end of the high fat treatment, whereas the rest of the animals (n = 10) were shifted to normocaloric diet (NCD) for 10 weeks, after which the same analyses were carried out. A significant reduction of body weight was found after the transition from high to normal fat diet, and this decrease correlated well with an improvement in insulin sensitivity. In fact, we found a reduction in serum insulin levels and the recovery of insulin responsiveness in terms of glucose disposal measured by insulin tolerance test and Glut4 mRNA and protein expression. These results indicate that obesity-related insulin resistance may be rescued by shifting from HFD to NCD. PMID:27303363

  10. Muscle Sympathetic Nerve Activity Is Associated with Liver Insulin Sensitivity in Obese Non-Diabetic Men.

    PubMed

    Chen, Daniel L T; Brown, Rachael; Liess, Carsten; Poljak, Anne; Xu, Aimin; Zhang, Jialiang; Trenell, Michael; Jenkins, Arthur; Chisholm, Donald; Samocha-Bonet, Dorit; Macefield, Vaughan G; Greenfield, Jerry R

    2017-01-01

    Introduction: Muscle sympathetic nerve activity (MSNA) may play a role in insulin resistance in obesity. However, the direction and nature of the relationship between MSNA and insulin resistance in obesity remain unclear. We hypothesized that resting MSNA would correlate inversely with both muscle and liver insulin sensitivity and that it would be higher in insulin-resistant vs. insulin-sensitive subjects. Materials and methods: Forty-five non-diabetic obese subjects were studied. As no significant relationships were found in women, the data presented in on 22 men aged 48 ± 12 years. Two-step (15 and 80 mU/m(2)/min) hyperinsulinaemic-euglycaemic clamps were performed using deuterated glucose to determine liver and muscle insulin sensitivity. Clinical and metabolic parameters were assessed. MSNA was measured via a microelectrode inserted percutaneously into the common peroneal nerve. Results: MSNA burst frequency correlated inversely with liver insulin sensitivity (r = -0.53, P = 0.02) and positively with the hepatokines C-reactive protein (CRP) and fibroblast growth factor (FGF)-19 (r = 0.57, P = 0.006, and r = -0.47, P = 0.03, respectively). MSNA burst frequency was lower in Liversen compared to Liverres (27 ± 5 vs. 38 ± 2 bursts per minute; P = 0.03). Muscle insulin sensitivity was unrelated to MSNA. Discussion: Sympathetic neural activation is related to liver insulin sensitivity and circulating hepatokines CRP and FGF-19 in non-diabetic obese men. These results suggest a potential hepato-endocrine-autonomic axis. Future studies are needed to clarify the influence of MSNA on liver insulin sensitivity in men.

  11. Muscle Sympathetic Nerve Activity Is Associated with Liver Insulin Sensitivity in Obese Non-Diabetic Men

    PubMed Central

    Chen, Daniel L. T.; Brown, Rachael; Liess, Carsten; Poljak, Anne; Xu, Aimin; Zhang, Jialiang; Trenell, Michael; Jenkins, Arthur; Chisholm, Donald; Samocha-Bonet, Dorit; Macefield, Vaughan G.; Greenfield, Jerry R.

    2017-01-01

    Introduction: Muscle sympathetic nerve activity (MSNA) may play a role in insulin resistance in obesity. However, the direction and nature of the relationship between MSNA and insulin resistance in obesity remain unclear. We hypothesized that resting MSNA would correlate inversely with both muscle and liver insulin sensitivity and that it would be higher in insulin-resistant vs. insulin-sensitive subjects. Materials and methods: Forty-five non-diabetic obese subjects were studied. As no significant relationships were found in women, the data presented in on 22 men aged 48 ± 12 years. Two-step (15 and 80 mU/m2/min) hyperinsulinaemic-euglycaemic clamps were performed using deuterated glucose to determine liver and muscle insulin sensitivity. Clinical and metabolic parameters were assessed. MSNA was measured via a microelectrode inserted percutaneously into the common peroneal nerve. Results: MSNA burst frequency correlated inversely with liver insulin sensitivity (r = −0.53, P = 0.02) and positively with the hepatokines C-reactive protein (CRP) and fibroblast growth factor (FGF)-19 (r = 0.57, P = 0.006, and r = −0.47, P = 0.03, respectively). MSNA burst frequency was lower in Liversen compared to Liverres (27 ± 5 vs. 38 ± 2 bursts per minute; P = 0.03). Muscle insulin sensitivity was unrelated to MSNA. Discussion: Sympathetic neural activation is related to liver insulin sensitivity and circulating hepatokines CRP and FGF-19 in non-diabetic obese men. These results suggest a potential hepato-endocrine-autonomic axis. Future studies are needed to clarify the influence of MSNA on liver insulin sensitivity in men. PMID:28293196

  12. Measures of abdominal obesity within body mass index categories, 1981 and 2007-2009.

    PubMed

    Shields, Margot; Tremblay, Mark S; Connor Gorber, Sarah; Janssen, Ian

    2012-06-01

    This article describes measures of abdominal obesity--waist circumference, waist-to-hip ratio, and waist-to-height ratio--within body mass index (BMI) categories, using data from two population-based health surveys. Among normal-weight men, the percentages at increased/high health risk based on these three measures were not statistically different in 2007-2009 than in 1981. By contrast, among normal-weight women, increases were observed in the percentage at increased/high health risk based on each of the three measures. The percentage of overweight men at increased/high risk based on waist circumference rose from 49% in 1981 to 62% in 2007-2009, and among overweight women, the percentage at increased/high risk rose for each of the three measures (64% to 93% for waist circumference, 22% to 51% for waist-to-hip ratio, and 68% to 87% for waist-to-height ratio). Although substantial percentages of men and women in obese class I were at increased/high health risk based on abdominal obesity measures in 1981, by 2007-2009, almost everyone in this BMI category was at increased/high risk.

  13. Are obesity-related insulin resistance and type 2 diabetes autoimmune diseases?

    PubMed

    Tsai, Sue; Clemente-Casares, Xavier; Revelo, Xavier S; Winer, Shawn; Winer, Daniel A

    2015-06-01

    Obesity and associated insulin resistance predispose individuals to develop chronic metabolic diseases, such as type 2 diabetes and cardiovascular disease. Although these disorders affect a significant proportion of the global population, the underlying mechanisms of disease remain poorly understood. The discovery of elevated tumor necrosis factor-α in adipose tissue as an inducer of obesity-associated insulin resistance marked a new era of understanding that a subclinical inflammatory process underlies the insulin resistance and metabolic dysfunction that precedes type 2 diabetes. Advances in the field identified components of both the innate and adaptive immune response as key players in regulating such inflammatory processes. As antigen specificity is a hallmark of an adaptive immune response, its role in modulating the chronic inflammation that accompanies obesity and type 2 diabetes begs the question of whether insulin resistance and type 2 diabetes can have autoimmune components. In this Perspective, we summarize current data that pertain to the activation and perpetuation of adaptive immune responses during obesity and discuss key missing links and potential mechanisms for obesity-related insulin resistance and type 2 diabetes to be considered as potential autoimmune diseases.

  14. Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin resistance

    PubMed Central

    Chatzigeorgiou, Antonios; Seijkens, Tom; Zarzycka, Barbara; Engel, David; Poggi, Marjorie; van den Berg, Susan; van den Berg, Sjoerd; Soehnlein, Oliver; Winkels, Holger; Beckers, Linda; Lievens, Dirk; Driessen, Ann; Kusters, Pascal; Biessen, Erik; Garcia-Martin, Ruben; Klotzsche-von Ameln, Anne; Gijbels, Marion; Noelle, Randolph; Boon, Louis; Hackeng, Tilman; Schulte, Klaus-Martin; Xu, Aimin; Vriend, Gert; Nabuurs, Sander; Chung, Kyoung-Jin; Willems van Dijk, Ko; Rensen, Patrick C. N.; Gerdes, Norbert; de Winther, Menno; Block, Norman L.; Schally, Andrew V.; Weber, Christian; Bornstein, Stefan R.; Nicolaes, Gerry; Chavakis, Triantafyllos; Lutgens, Esther

    2014-01-01

    The immune system plays an instrumental role in obesity and insulin resistance. Here, we unravel the role of the costimulatory molecule CD40 and its signaling intermediates, TNF receptor-associated factors (TRAFs), in diet-induced obesity (DIO). Although not exhibiting increased weight gain, male CD40−/− mice in DIO displayed worsened insulin resistance, compared with wild-type mice. This worsening was associated with excessive inflammation of adipose tissue (AT), characterized by increased accumulation of CD8+ T cells and M1 macrophages, and enhanced hepatosteatosis. Mice with deficient CD40-TRAF2/3/5 signaling in MHCII+ cells exhibited a similar phenotype in DIO as CD40−/− mice. In contrast, mice with deficient CD40-TRAF6 signaling in MHCII+ cells displayed no insulin resistance and showed a reduction in both AT inflammation and hepatosteatosis in DIO. To prove the therapeutic potential of inhibition of CD40-TRAF6 in obesity, DIO mice were treated with a small-molecule inhibitor that we designed to specifically block CD40-TRAF6 interactions; this compound improved insulin sensitivity, reduced AT inflammation, and decreased hepatosteatosis. Our study reveals that the CD40-TRAF2/3/5 signaling pathway in MHCII+ cells protects against AT inflammation and metabolic complications associated with obesity whereas CD40-TRAF6 interactions in MHCII+ cells aggravate these complications. Inhibition of CD40-TRAF6 signaling by our compound may provide a therapeutic option in obesity-associated insulin resistance. PMID:24492375

  15. Increased abundance of insulin/insulin-like growth factor-I hybrid receptors in skeletal muscle of obese subjects is correlated with in vivo insulin sensitivity.

    PubMed

    Federici, M; Porzio, O; Lauro, D; Borboni, P; Giovannone, B; Zucaro, L; Hribal, M L; Sesti, G

    1998-08-01

    We reported that in noninsulin-dependent diabetes melitus (NIDDM) patients expression of insulin/insulin-like growth factor I (IGF-I) hybrid receptors is increased in insulin target tissues. Whether this is a defect associated with NIDDM or represents a generalized abnormality associated with insulin resistant states is still unsettled. To address this, we applied a microwell-based immunoassay to measure abundance of insulin receptors, type 1 IGF receptors, and hybrid receptors in muscle of eight normal and eight obese subjects. Maximal insulin binding to insulin receptors was lower in obese than in control subjects (B/T = 1.8 +/- 0.20 and 2.6 +/- 0.30; P < 0.03, respectively) and was negatively correlated with insulinemia (r = -0.60; P < 0.01). Maximal IGF-I binding to type 1 IGF receptors was higher in obese than in controls (B/T = 1.9 +/- 0.20 and 0.86 +/- 0.10; P < 0.0001, respectively) and was negatively correlated with plasma IGF-I levels (r = -0.69; P < 0.003). Hybrid receptor abundance was higher in obese than in normal subjects (B/T = 1.21 +/- 0.14 and 0.44 +/- 0.06; P < 0.0003, respectively) and was negatively correlated with insulin binding (r = -0.60; P < 0.01) and positively correlated with IGF-I binding (r = 0.92; P < 0.0001). Increased abundance of hybrids was correlated with insulinemia (r = 0.70; P < 0.002) and body mass index (r = 0.71; P < 0.0019), whereas it was negatively correlated with in vivo insulin sensitivity measured by ITT (r = -0.67; P < 0.016). These results indicate that downregulation of insulin receptors or upregulation of type 1 IGF receptors because of changes in plasma insulin and IGF-I levels may result in modifications in hybrid receptor abundance.

  16. Garlic extract attenuates brain mitochondrial dysfunction and cognitive deficit in obese-insulin resistant rats.

    PubMed

    Pintana, Hiranya; Sripetchwandee, Jirapas; Supakul, Luerat; Apaijai, Nattayaporn; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2014-12-01

    Oxidative stress in the obese-insulin resistant condition has been shown to affect cognitive as well as brain mitochondrial functions. Garlic extract has exerted a potent antioxidant effect. However, the effects of garlic extract on the brain of obese-insulin resistant rats have never been investigated. We hypothesized that garlic extract improves cognitive function and brain mitochondrial function in obese-insulin resistant rats induced by long-term high-fat diet (HFD) consumption. Male Wistar rats were fed either normal diet or HFD for 16 weeks (n = 24/group). At week 12, rats in each dietary group received either vehicle or garlic extract (250 and 500 mg·kg(-1)·day(-1)) for 28 days. Learning and memory behaviors, metabolic parameters, and brain mitochondrial function were determined at the end of treatment. HFD led to increased body weight, visceral fat, plasma insulin, cholesterol, and malondialdehyde (MDA) levels, indicating the development of insulin resistance. Furthermore, HFD rats had cognitive deficit and brain mitochondrial dysfunction. HFD rats treated with both doses of garlic extract had decreased body weight, visceral fat, plasma cholesterol, and MDA levels. Garlic extract also improved cognitive function and brain mitochondrial function, which were impaired in obese-insulin resistant rats caused by HFD consumption.

  17. G Protein–Coupled Receptor Kinase 2 Plays a Relevant Role in Insulin Resistance and Obesity

    PubMed Central

    Garcia-Guerra, Lucia; Nieto-Vazquez, Iria; Vila-Bedmar, Rocio; Jurado-Pueyo, María; Zalba, Guillermo; Díez, Javier; Murga, Cristina; Fernández-Veledo, Sonia; Mayor, Federico; Lorenzo, Margarita

    2010-01-01

    OBJECTIVE Insulin resistance is associated with the pathogenesis of metabolic disorders as type 2 diabetes and obesity. Given the emerging role of signal transduction in these syndromes, we set out to explore the possible role that G protein–coupled receptor kinase 2 (GRK2), first identified as a G protein–coupled receptor regulator, could have as a modulator of insulin responses. RESEARCH DESIGN AND METHODS We analyzed the influence of GRK2 levels in insulin signaling in myoblasts and adipocytes with experimentally increased or silenced levels of GRK2, as well as in GRK2 hemizygous animals expressing 50% lower levels of this kinase in three different models of insulin resistance: tumor necrosis factor-α (TNF-α) infusion, aging, and high-fat diet (HFD). Glucose transport, whole-body glucose and insulin tolerance, the activation status of insulin pathway components, and the circulating levels of important mediators were measured. The development of obesity and adipocyte size with age and HFD was analyzed. RESULTS Altering GRK2 levels markedly modifies insulin-mediated signaling in cultured adipocytes and myocytes. GRK2 levels are increased by ∼2-fold in muscle and adipose tissue in the animal models tested, as well as in lymphocytes from metabolic syndrome patients. In contrast, hemizygous GRK2 mice show enhanced insulin sensitivity and do not develop insulin resistance by TNF-α, aging, or HFD. Furthermore, reduced GRK2 levels induce a lean phenotype and decrease age-related adiposity. CONCLUSIONS Overall, our data identify GRK2 as an important negative regulator of insulin effects, key to the etiopathogenesis of insulin resistance and obesity, which uncovers this protein as a potential therapeutic target in the treatment of these disorders. PMID:20627936

  18. B cell secretion and insulin sensitivity in hypertensive and normotensive obese subjects.

    PubMed

    Bonora, E; Moghetti, P; Zenere, M; Tosi, F; Travia, D; Muggeo, M

    1990-09-01

    To test the hypothesis that in obesity hypertension is associated with more pronounced hyperinsulinaemia and insulin resistance we compared plasma insulin levels and insulin sensitivity in a group of 6 obese subjects with untreated hypertension and in a group of 6 obese subjects with normal blood pressure. The two groups were similar for sex, age, body mass index and glucose tolerance. Six nonobese subjects served as controls. The study consisted of a 2-h hyperglycaemic clamp (steady-state plasma glucose = 11 mmol/l) and a 15-min insulin tolerance test (0.1 U/kg body wt). During hyperglycaemic clamp, insulin and C-peptide plasma levels were similar in normotensive and hypertensive obese subjects: the area under the plasma insulin curve was 36,000 +/- 3000 pmol/l X 120 min in the former and 34,000 +/- 1000 pmol/l X 120 min in the latter; the area under the plasma C-peptide curve was 298,000 +/- 26,000 pmol/l X 120 min in the former and 246,000 +/- 26,000 pmol/l X 120 min in the latter (P = n.s.). The ratio M/I between the amount of glucose metabolized (M) and the mean plasma insulin levels (I) during hyperglycaemic clamp was similar in the two groups: 0.59 +/- 0.09 in normotensive and 0.58 +/- 0.08 mg/min X m2 per pmol/l in hypertensive obese subjects (P = n.s.). Also the rate coefficient of glucose disappearance from plasma (K(itt)) after i.v. insulin injection was similar in the two groups (4.08 +/- 0.51 vs. 3.87 +/- 0.53 per cent/min).(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Insulin Resistance, Metabolic Syndrome, and Polycystic Ovary Syndrome in Obese Youth.

    PubMed

    Platt, Adrienne M

    2015-07-01

    School nurses are well aware of the childhood obesity epidemic in the United States, as one in three youth are overweight or obese. Co-morbidities found in overweight or obese adults were not commonly found in youth three decades ago but are now increasingly "normal" as the obesity epidemic continues to evolve. This article is the second of six related articles discussing the co-morbidities of childhood obesity and discusses the complex association between obesity and insulin resistance, metabolic syndrome, and polycystic ovary syndrome. Insulin resistance increases up to 50% during puberty, which may help to explain why youth are more likely to develop co-morbidities as teens. Treatment of these disorders is focused on changing lifestyle habits, as a child cannot change his or her pubertal progression, ethnicity, or family history. School nurses and other personnel can assist youth with insulin resistance, metabolic syndrome, and polycystic ovary syndrome by supporting their efforts to make changes, reinforcing that insulin resistance is not necessarily type 2 diabetes even if the child is taking medication, and intervening with negative peer pressure.

  20. Proteasome Dysfunction Associated to Oxidative Stress and Proteotoxicity in Adipocytes Compromises Insulin Sensitivity in Human Obesity

    PubMed Central

    Díaz-Ruiz, Alberto; Guzmán-Ruiz, Rocío; Moreno, Natalia R.; García-Rios, Antonio; Delgado-Casado, Nieves; Membrives, Antonio; Túnez, Isaac; El Bekay, Rajaa; Fernández-Real, José M.; Tovar, Sulay; Diéguez, Carlos; Tinahones, Francisco J.; Vázquez-Martínez, Rafael; López-Miranda, José

    2015-01-01

    Abstract Aims: Obesity is characterized by a low-grade systemic inflammatory state and adipose tissue (AT) dysfunction, which predispose individuals to the development of insulin resistance (IR) and metabolic disease. However, a subset of obese individuals, referred to as metabolically healthy obese (MHO) individuals, are protected from obesity-associated metabolic abnormalities. Here, we aim at identifying molecular factors and pathways in adipocytes that are responsible for the progression from the insulin-sensitive to the insulin-resistant, metabolically unhealthy obese (MUHO) phenotype. Results: Proteomic analysis of paired samples of adipocytes from subcutaneous (SC) and omental (OM) human AT revealed that both types of cells are altered in the MUHO state. Specifically, the glutathione redox cycle and other antioxidant defense systems as well as the protein-folding machinery were dysregulated and endoplasmic reticulum stress was increased in adipocytes from IR subjects. Moreover, proteasome activity was also compromised in adipocytes of MUHO individuals, which was associated with enhanced accumulation of oxidized and ubiquitinated proteins in these cells. Proteasome activity was also impaired in adipocytes of diet-induced obese mice and in 3T3-L1 adipocytes exposed to palmitate. In line with these data, proteasome inhibition significantly impaired insulin signaling in 3T3-L1 adipocytes. Innovation: This study provides the first evidence of the occurrence of protein homeostasis deregulation in adipocytes in human obesity, which, together with oxidative damage, interferes with insulin signaling in these cells. Conclusion: Our results suggest that proteasomal dysfunction and impaired proteostasis in adipocytes, resulting from protein oxidation and/or misfolding, constitute major pathogenic mechanisms in the development of IR in obesity. Antioxid. Redox Signal. 23, 597–612. PMID:25714483

  1. Preserved endothelial function in human obesity in the absence of insulin resistance

    PubMed Central

    2013-01-01

    Background Insulin resistance (IR) is frequently associated with endothelial dysfunction and has been proposed to play a major role in cardiovascular disease (CVD). On the other hand, obesity has long been related to IR and increased CVD. However it is not known if IR is a necessary condition for endothelial dysfunction in human obesity, allowing for preserved endothelial function in obese people when absent. Therefore, the purpose of the study was to assess the relationship between IR and endothelial dysfunction in human obesity and the mechanisms involved. Methods Twenty non-insulin resistant morbid obese (NIR-MO), 32 insulin resistant morbid obese (IR-MO), and 12 healthy subjects were included. Serum concentrations of glucose, insulin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), resistin and adiponectin were determined. IR was evaluated by HOMA-index. Endothelium-dependent relaxation to bradykinin (BK) in mesenteric microvessels was assessed in wire myograph. Results Serum IL-6, and TNF-α levels were elevated only in IR-MO patients while resistin was elevated and adiponectin reduced in all MO individuals. Mesenteric arteries from IR-MO, but not from NIR-MO subjects displayed blunted relaxation to BK. Vasodilatation was improved in IR-MO arteries by the superoxide scavenger, superoxide dismutase (SOD) or the mitochondrial-targeted SOD mimetic, mito-TEMPO. NADPH oxidase inhibitors (apocynin and VAS2870) and the nitric oxide synthase (NOS) cofactor, tetrahydrobiopterin failed to modify BK-induced vasodilatations. Superoxide generation was higher in vessels from IR-MO subjects and reduced by mito-TEMPO. Blockade of TNF-α with infliximab, but not inhibition of inducible NOS or cyclooxygenase, improved endothelial relaxation and decreased superoxide formation. Conclusions Endothelial dysfunction is observed in human morbid obesity only when insulin resistance is present. Mechanisms involved include augmented mitochondrial superoxide generation, and

  2. Vagotomy diminishes obesity in cafeteria rats by decreasing cholinergic potentiation of insulin release.

    PubMed

    Balbo, Sandra Lucinei; Ribeiro, Rosane Aparecida; Mendes, Mariana Carla; Lubaczeuski, Camila; Maller, Ana Claudia Paiva Alegre; Carneiro, Everardo Magalhães; Bonfleur, Maria Lúcia

    2016-12-01

    Herein, we investigated whether subdiaphragmatic vagotomy has benefits on obesity, body glucose homeostasis, and insulin secretion in cafeteria (CAF)-obese rats. Wistar rats were fed a standard or CAF diet for 12 weeks. Subsequently, CAF rats were randomly submitted to truncal vagotomy (CAF Vag) or sham operation (CAF Sham). CAF Sham rats were hyperphagic, obese, and presented metabolic disturbances, including hyperinsulinemia, glucose intolerance, insulin resistance, hyperglycemia, and hypertriglyceridemia. Twelve weeks after vagotomy, CAF Vag rats presented reductions in body weight and perigonadal fat stores. Vagotomy did not modify glucose tolerance but normalized fed glycemia, insulinemia, and insulin sensitivity. Isolated islets from CAF Sham rats secreted more insulin in response to the cholinergic agent, carbachol, and when intracellular cyclic adenine monophosphate (cAMP) is enhanced by forskolin or 3-isobutyl-1-methylxanthine. Vagotomy decreased glucose-induced insulin release due to a reduction in the cholinergic action on β-cells. This effect also normalized islet secretion in response to cAMP. Therefore, vagotomy in rats fed on a CAF-style diet effectively decreases adiposity and restores insulin sensitivity. These effects were mainly associated with the lack of cholinergic action on the endocrine pancreas, which decreases insulinemia and may gradually reduce fat storage and improve insulin sensitivity.

  3. Fas (CD95) expression in myeloid cells promotes obesity-induced muscle insulin resistance

    PubMed Central

    Wueest, Stephan; Mueller, Rouven; Blüher, Matthias; Item, Flurin; Chin, Annie S H; Wiedemann, Michael S F; Takizawa, Hitoshi; Kovtonyuk, Larisa; Chervonsky, Alexander V; Schoenle, Eugen J; Manz, Markus G; Konrad, Daniel

    2014-01-01

    Low-grade inflammation in adipose tissue and liver has been implicated in obesity-associated insulin resistance and type 2 diabetes. Yet, the contribution of inflammatory cells to the pathogenesis of skeletal muscle insulin resistance remains elusive. In a large cohort of obese human individuals, blood monocyte Fas (CD95) expression correlated with systemic and skeletal muscle insulin resistance. To test a causal role for myeloid cell Fas expression in the development of skeletal muscle insulin resistance, we generated myeloid/haematopoietic cell-specific Fas-depleted mice. Myeloid/haematopoietic Fas deficiency prevented the development of glucose intolerance in high fat-fed mice, in ob/ob mice, and in mice acutely challenged by LPS. In vivo, ex vivo and in vitro studies demonstrated preservation of muscle insulin responsiveness with no effect on adipose tissue or liver. Studies using neutralizing antibodies demonstrated a role for TNFα as mediator between myeloid Fas and skeletal muscle insulin resistance, supported by significant correlations between monocyte Fas expression and circulating TNFα in humans. In conclusion, our results demonstrate an unanticipated crosstalk between myeloid cells and skeletal muscle in the development of obesity-associated insulin resistance. PMID:24203314

  4. Age, Obesity, and Sex Effects on Insulin Sensitivity and Skeletal Muscle Mitochondrial Function

    PubMed Central

    Karakelides, Helen; Irving, Brian A.; Short, Kevin R.; O'Brien, Peter; Nair, K. Sreekumaran

    2010-01-01

    OBJECTIVE Reductions in insulin sensitivity in conjunction with muscle mitochondrial dysfunction have been reported to occur in many conditions including aging. The objective was to determine whether insulin resistance and mitochondrial dysfunction are directly related to chronological age or are related to age-related changes in body composition. RESEARCH DESIGN AND METHODS Twelve young lean, 12 young obese, 12 elderly lean, and 12 elderly obese sedentary adults were studied. Insulin sensitivity was measured by a hyperinsulinemic-euglycemic clamp, and skeletal muscle mitochondrial ATP production rates (MAPRs) were measured in freshly isolated mitochondria obtained from vastus lateralis biopsy samples using the luciferase reaction. RESULTS Obese participants, independent of age, had reduced insulin sensitivity based on lower rates of glucose infusion during a hyperinsulinemic-euglycemic clamp. In contrast, age had no independent effect on insulin sensitivity. However, the elderly participants had lower muscle MAPRs than the young participants, independent of obesity. Elderly participants also had higher levels inflammatory cytokines and total adiponectin. In addition, higher muscle MAPRs were also noted in men than in women, whereas glucose infusion rates were higher in women. CONCLUSIONS The results demonstrate that age-related reductions in insulin sensitivity are likely due to an age-related increase in adiposity rather than a consequence of advanced chronological age. The results also indicate that an age-related decrease in muscle mitochondrial function is neither related to adiposity nor insulin sensitivity. Of interest, a higher mitochondrial ATP production capacity was noted in the men, whereas the women were more insulin sensitive, demonstrating further dissociation between insulin sensitivity and muscle mitochondrial function. PMID:19833885

  5. Depot Dependent Effects of Dexamethasone on Gene Expression in Human Omental and Abdominal Subcutaneous Adipose Tissues from Obese Women

    PubMed Central

    Karastergiou, Kalypso; Gower, Adam; Fried, Susan K.

    2016-01-01

    Glucocorticoids promote fat accumulation in visceral compared to subcutaneous depots, but the molecular mechanisms involved remain poorly understood. To identify long-term changes in gene expression that are differentially sensitive or responsive to glucocorticoids in these depots, paired samples of human omental (Om) and abdominal subcutaneous (Abdsc) adipose tissues obtained from obese women during elective surgery were cultured with the glucocorticoid receptor agonist dexamethasone (Dex, 0, 1, 10, 25 and 1000 nM) for 7 days. Dex regulated 32% of the 19,741 genes on the array, while 53% differed by Depot and 2.5% exhibited a Depot*Dex concentration interaction. Gene set enrichment analysis showed Dex regulation of the expected metabolic and inflammatory pathways in both depots. Cluster analysis of the 460 transcripts that exhibited an interaction of Depot and Dex concentration revealed sets of mRNAs for which the responses to Dex differed in magnitude, sensitivity or direction between the two depots as well as mRNAs that responded to Dex only in one depot. These transcripts were also clearly depot different in fresh adipose tissue and are implicated in processes that could affect adipose tissue distribution or functions (e.g. adipogenesis, triacylglycerol synthesis and storage, insulin action). Elucidation of the mechanisms underlying the depot differences in the effect of Dex on the expression of specific genes and pathways that regulate adipose function may offer novel insights into understanding the biology of visceral adipose tissues and their links to metabolic health. PMID:28005982

  6. Physical activity in adolescence and abdominal obesity in adulthood: a case-control study among women shift workers.

    PubMed

    Garcez, Anderson da Silva; Olinto, Maria Teresa Anselmo; Canuto, Raquel; Olinto, Beatriz Anselmo; Pattussi, Marcos Pascoal; Paniz, Vera Maria Vieira

    2015-01-01

    Physical activity may have a protective effect against abdominal obesity, an important risk factor for cardiometabolic diseases. Thus, the aim of this study was to examine the association between the practice of physical activities in adolescence and abdominal obesity in adulthood among women shift workers in Southern Brazil in 2011. This case-control study included 215 cases (waist circumference greater than or equal to 88 cm) and 326 controls. For both the case and control groups, participation in leisure-time physical activities was most frequent in adolescence and was significantly less in adulthood. After adjusting for potential confounding factors, women who participated in five or more physical activities in adolescence were 50 percent less likely to have abdominal obesity than women who participated in one activity or no physical activities (Odds Ratio = 0.50; 95% confidential interval: 0.27-0.93, p value = .029). Participation in various types of leisure-time physical activities in adolescence may protect against abdominal obesity in adulthood, even if the number of physical activities decreases over time. This finding demonstrated the importance of physical activity as well as the period of life in which these should be encouraged for the prevention of health disorders, such as abdominal obesity.

  7. Influence of Maternal Obesity on Insulin Sensitivity and Secretion in Offspring

    PubMed Central

    Mingrone, Geltrude; Manco, Melania; Valera Mora, Maria Elena; Guidone, Caterina; Iaconelli, Amerigo; Gniuli, Donatella; Leccesi, Laura; Chiellini, Chiara; Ghirlanda, Giovanni

    2008-01-01

    OBJECTIVE—The purpose of this study was to clarify the effects of maternal obesity on insulin sensitivity and secretion in offspring. RESEARCH DESIGN AND METHODS—Fifty-one offspring of both sexes of obese (Ob group) and 15 offspring of normal-weight (control group) mothers were studied. Plasma glucose, insulin, and C-peptide were measured during an oral glucose tolerance test (OGTT). Insulin sensitivity was calculated using the oral glucose insulin sensitivity index, and insulin secretion and β-cell glucose sensitivity were computed by a mathematical model. Fasting leptin and adiponectin were also measured. Body composition was assessed by dual-X-ray absorptiometry. RESULTS—No birth weight statistical difference was observed in the two groups. Of the Ob group, 69% were obese and 19% were overweight. The Ob group were more insulin resistant than the control group (398.58 ± 79.32 vs. 513.81 ± 70.70 ml−1 · min−1 · m−2 in women, P < 0.0001; 416.42 ± 76.17 vs. 484.242 ± 45.76 ml−1 · min−1 · m−2 in men, P < 0.05). Insulin secretion after OGTT was higher in Ob group than in control group men (63.94 ± 21.20 vs. 35.71 ± 10.02 nmol · m−2, P < 0.01) but did not differ significantly in women. β-Cell glucose sensitivity was not statistically different between groups. A multivariate analysis of variance showed that maternal obesity and offspring sex concurred together with BMI and β-cell glucose sensitivity to determine the differences in insulin sensitivity and secretion observed in offspring. CONCLUSIONS—Obese mothers can give birth to normal birth weight babies who later develop obesity and insulin resistance. The maternal genetic/epigenetic transmission shows a clear sexual dimorphism, with male offspring having a higher value of insulin sensitivity (although not statistically significant) associated with significantly higher insulin secretion than female offspring. PMID:18535193

  8. Interleukin-6 signaling promotes alternative macrophage activation to limit obesity-associated insulin resistance and endotoxemia

    PubMed Central

    Mauer, Jan; Chaurasia, Bhagirath; Goldau, Julia; Vogt, Merly C.; Ruud, Johan; Nguyen, Khoa D.; Theurich, Sebastian; Hausen, A. Christine; Schmitz, Joel; Brönneke, Hella S.; Estevez, Emma; Allen, Tamara L.; Mesaros, Andrea; Partridge, Linda; Febbraio, Mark A.; Chawla, Ajay; Wunderlich, F. Thomas; Brüning, Jens C.

    2014-01-01

    Obesity and insulin resistance are closely associated with the development of low-grade inflammation. Interleukin 6 (IL-6) is linked to obesity-associated inflammation, however its role in this context remains controversial. Here, we show that mice with inactivated Il6ra gene in myeloid cells (Il6raΔmyel) displayed exaggerated deterioration of glucose homeostasis upon diet-induced obesity due to enhanced insulin resistance. Insulin target tissues showed increased inflammation and a shift in macrophage polarization. IL-6 induced IL-4-receptor expression and augmented the response to IL-4 in macrophages in a cell-autonomous manner. Il6raΔmyel mice were resistant to IL-4-mediated alternative macrophage polarization and exhibited increased susceptibility to LPS-induced endotoxemia. These results reveal IL-6 signaling as an important determinant for alternative macrophage-activation and assign IL-6 an unexpected homeostatic role to limit inflammation. PMID:24681566

  9. Exercise-Induced Weight Loss is More Effective than Dieting for Improving Adipokine Profile, Insulin Resistance, and Inflammation in Obese Men.

    PubMed

    Khoo, Joan; Dhamodaran, Subbiah; Chen, Dan-Dan; Yap, Siew-Yoon; Chen, Richard Yuan-Tud; Tian, Roger Ho-Heng

    2015-12-01

    The adipokines chemerin and adiponectin are reciprocally related in the pathogenesis of insulin resistance and inflammation in obesity. Weight loss increases adiponectin and reduces chemerin, insulin resistance, and inflammation, but the effects of caloric restriction and physical activity are difficult to separate in combined lifestyle modification. We compared effects of diet- or exercise-induced weight loss on chemerin, adiponectin, insulin resistance, and inflammation in obese men. Eighty abdominally obese Asian men (body mass index [BMI] ≥ 30 kg/m(2), waist circumference [WC] ≥ 90 cm, mean age 42.6 years) were randomized to reduce daily intake by ~500 kilocalories (n = 40) or perform moderate-intensity aerobic and resistance exercise (200-300 min/week) (n = 40) to increase energy expenditure by a similar amount for 24 weeks. The diet and exercise groups had similar decreases in energy deficit (-456 ± 338 vs. -455 ± 315 kcal/day), weight (-3.6 ± 3.4 vs. -3.3 ± 4.6 kg), and WC (-3.4 ± 4.4 vs. -3.6 ± 3.2 cm). The exercise group demonstrated greater reductions in fat mass (-3.9 ± 3.5 vs. -2.7 ± 5.3 kg), serum chemerin (-9.7 ± 11.1 vs. -4.3 ± 12.4 ng/ml), the inflammatory marker high-sensitivity C-reactive protein (-2.11 ± 3.13 vs. -1.49 ± 3.08 mg/L), and insulin resistance as measured by homeostatic model assessment (-2.45 ± 1.88 vs. -1.38 ± 3.77). Serum adiponectin increased only in the exercise group. Exercise-induced fat mass loss was more effective than dieting for improving adipokine profile, insulin resistance, and systemic inflammation in obese men, underscoring metabolic benefits of increased physical activity.

  10. Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management.

    PubMed

    Misra, A; Chowbey, P; Makkar, B M; Vikram, N K; Wasir, J S; Chadha, D; Joshi, Shashank R; Sadikot, S; Gupta, R; Gulati, Seema; Munjal, Y P

    2009-02-01

    Asian Indians exhibit unique features of obesity; excess body fat, abdominal adiposity, increased subcutaneous and intra-abdominal fat, and deposition of fat in ectopic sites (liver, muscle, etc.). Obesity is a major driver for the widely prevalent metabolic syndrome and type 2 diabetes mellitus (T2DM) in Asian Indians in India and those residing in other countries. Based on percentage body fat and morbidity data, limits of normal BMI are narrower and lower in Asian Indians than in white Caucasians. In this consensus statement, we present revised guidelines for diagnosis of obesity, abdominal obesity, the metabolic syndrome, physical activity, and drug therapy and bariatric surgery for obesity in Asian Indians after consultations with experts from various regions of India belonging to the following medical disciplines; internal medicine, metabolic diseases, endocrinology, nutrition, cardiology, exercise physiology, sports medicine and bariatric surgery, and representing reputed medical institutions, hospitals, government funded research institutions, and policy making bodies. It is estimated that by application of these guidelines, additional 10-15% of Indian population would be labeled as overweight/obese and would require appropriate management. Application of these guidelines on countrywide basis is also likely to have a deceleration effect on the escalating problem of T2DM and cardiovascular disease. These guidelines could be revised in future as appropriate, after another large and countrywide consensus process. Till that time, these should be used by clinicians, researchers and policymakers dealing with obesity and related diseases.

  11. Abdominal obesity and structure and function of the heart in healthy male Koreans

    PubMed Central

    Son, Jung-Woo; Sung, Joong Kyung; Lee, Jun-Won; Youn, Young Jin; Ahn, Min-Soo; Ahn, Sung Gyun; Yoo, Byung-Su; Lee, Seung-Hwan; Yoon, Junghan; Koh, Sang Baek; Kim, Jang-Young

    2016-01-01

    Abstract Although central obesity is a more powerful predictor of cardiovascular disease (CVD) than general obesity, there is limited information on structural and functional changes of the heart in central obesity. Therefore, we evaluated the association between abdominal obesity and geometric and functional changes of the heart in healthy males. A total of 1460 healthy males aged 40 to 70 years without known CVD from the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population were included. All individuals underwent conventional 2-dimensional echocardiography and tissue Doppler imaging to measure left atrial (LA) and left ventricle (LV) geometry and function. Increasing tertiles of waist circumference (WC) were associated with stepwise increases in LA volume, LV end-diastolic dimension, LV mass to height2, deceleration time of E wave, and lower E/A ratio (all P trends <0.001). In multivariable logistic regression models, the odds ratios for LA enlargement, LV hypertrophy, LV enlargement, and diastolic dysfunction comparing the upper tertile of WC (>89 cm) to the lowest tertile (<82 cm) were 2.81 (95% confidence interval [CI] 2.24–3.54), 3.65 (95% CI 2.54–5.26), 4.23 (95% CI 2.61–6.87), and 1.75 (95% CI 1.37–2.22), respectively. LV ejection fraction and relative wall thickness were not increased with increasing WC. The association between WC and LA enlargement, LV enlargement, and diastolic dysfunction persisted after stratification by body mass index tertiles. Central obesity may be a stronger predictor than general obesity of geometric and functional changes in the LV and LA. PMID:27684832

  12. Greater physical activity levels during pregnancy are associated with lower inflammation and insulin resistance in obese women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Compared to lean pregnant women, obese women develop greater insulin resistance and systemic inflammation during pregnancy. Identifying lifestyle factors that can reduce the metabolic effect of obesity during pregnancy is critical to protect both the mother and the fetus from insulin resistance and ...

  13. Sagittal Abdominal Diameter as a Surrogate Marker of Insulin Resistance in an Admixtured Population—Brazilian Metabolic Syndrome Study (BRAMS)

    PubMed Central

    Cassani, Roberta S. L.; Forti, Adriana C. e; Vilela, Brunna S.; Tambascia, Marcos Antonio

    2015-01-01

    Background Sagittal abdominal diameter (SAD) has been proposed as a surrogate marker of insulin resistance (IR). However, the utilization of SAD requires specific validation for each ethnicity. We aimed to investigate the potential use of SAD, compared with classical anthropometrical parameters, as a surrogate marker of IR and to establish the cutoff values of SAD for screening for IR. Methods A multicenter population survey on metabolic disorders was conducted. A race-admixtured sample of 824 adult women was assessed. The anthropometric parameters included: BMI, waist circumference (WC), waist-to-hip ratio and SAD. IR was determined by a hyperglycemic clamp and the HOMA-IR index. Results After adjustments for age and total body fat mass, SAD (r = 0.23 and r = -0.70) and BMI (r = 0.20 and r = -0.71) were strongly correlated with the IR measured by the HOMA-IR index and the clamp, respectively (p < 0.001). In the ROC analysis, the optimal cutoff for SAD in women was 21.0 cm. The women with an increased SAD presented 3.2 (CI 95%: 2.1-5.0) more likelihood of having IR, assessed by the HOMA-IR index compared with those with normal SAD (p < 0.001); whereas women with elevated BMI and WC were 2.1 (95% CI: 1.4-3.3) and 2.8 (95% CI: 1.7-4.5) more likely to have IR (p < 0.001), respectively. No statistically significant results were found for waist-to-hip ratio. Conclusions SAD can be a suitable surrogate marker of IR. Understanding and applying routine and simplified methods is essential because IR is associated with an increased risk of obesity-related diseases even in the presence of normal weight, slight overweight, as well as in obesity. Further prospective analysis will need to verify SAD as a determinant of clinical outcomes, such as type 2 diabetes and cardiovascular events, in the Brazilian population. PMID:25951458

  14. Use of a two-stage insulin infusion study to assess the relationship between insulin suppression of lipolysis and insulin-mediated glucose uptake in overweight/obese, nondiabetic women.

    PubMed

    McLaughlin, Tracey; Yee, Gail; Glassford, Alec; Lamendola, Cindy; Reaven, Gerald

    2011-12-01

    Differences in insulin regulation of free fatty acids (FFAs) are not readily apparent at the same insulin concentrations used to differentiate relative insulin-mediated glucose disposal. Resistance to insulin-mediated glucose disposal and higher daylong FFA concentrations occur more commonly in obese individuals. However, the relationship between the ability of insulin to suppress FFA release from adipose tissue and stimulate glucose disposal in muscle has not been clearly defined in this population. The current study was initiated to test the hypothesis that these 2 facets of insulin action are related, with greater defects in insulin-mediated glucose disposal associated with less effective insulin inhibition of FFA release from adipose tissue. Subjects included 56 healthy nondiabetic overweight/moderately obese women classified as insulin resistant or insulin sensitive based on whole-body glucose disposal. All underwent a modified 240-minute 2-stage insulin infusion with basal (∼15 µU/mL) and physiologically elevated (∼80 µU/mL) steady-state insulin concentrations. Plasma glucose, insulin, FFA, and glycerol were measured throughout. Whereas plasma glucose differed most during physiological hyperinsulinemia in insulin-resistant vs insulin-sensitive subjects, plasma FFA/glycerol differed most during basal insulin concentrations. The FFA concentrations during the basal insulin steady state correlated highly (r = 0.85, P < .001) with glucose concentrations during the hyperinsulinemic steady state. Overweight/moderately obese women exhibit dramatic differences in the ability of insulin to suppress plasma FFA, which correlate highly with differences in insulin-mediated glucose disposal. Variability in insulin regulation of FFA is most apparent at basal insulin concentrations, whereas differences in glucose disposal are most apparent during physiologic hyperinsulinemia. Both can be quantified using a simple 2-stage insulin infusion study, with first-stage FFA

  15. Adiponectin: a biomarker of obesity-induced insulin resistance in adipose tissue and beyond.

    PubMed

    Lu, Jin-Ying; Huang, Kuo-Chin; Chang, Lin-Chau; Huang, Ying-Shing; Chi, Yu-Chiao; Su, Ta-Chan; Chen, Chi-Ling; Yang, Wei-Shiung

    2008-09-01

    Adiponectin is one of the most thoroughly studied adipocytokines. Low plasma levels of adiponectin are found to associate with obesity, metabolic syndrome, diabetes and many other human diseases. From animal experiments and human studies, adiponectin has been shown to be a key regulator of insulin sensitivity. In this article, we review the evidence and propose that hypo-adiponectinemia is not a major cause of obesity. Instead, it is the result of obesity-induced insulin resistance in the adipose tissue. Hypo-adiponectinemia then mediates the metabolic effects of obesity on the other peripheral tissues, such as liver and skeletal muscle and may also exert some direct effects on end-organ damage. We propose that deciphering the molecular details governing the adiponectin gene expression and protein secretion will lead us to more comprehensive understanding of the mechanisms of insulin resistance in the adipose tissue and provide us new avenues for the therapeutic intervention of obesity and insulin resistance-related human disorders.

  16. Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity, and insulin resistance.

    PubMed

    Francés, Daniel E; Motiño, Omar; Agrá, Noelia; González-Rodríguez, Águeda; Fernández-Álvarez, Ana; Cucarella, Carme; Mayoral, Rafael; Castro-Sánchez, Luis; García-Casarrubios, Ester; Boscá, Lisardo; Carnovale, Cristina E; Casado, Marta; Valverde, Ángela M; Martín-Sanz, Paloma

    2015-05-01

    Accumulation evidence links obesity-induced inflammation as an important contributor to the development of insulin resistance, which plays a key role in the pathophysiology of obesity-related diseases such as type 2 diabetes and nonalcoholic fatty liver disease. Cyclooxygenase (COX)-1 and -2 catalyze the first step in prostanoid biosynthesis. Because adult hepatocytes fail to induce COX-2 expression regardless of the proinflammatory stimuli used, we have evaluated whether this lack of expression under mild proinflammatory conditions might constitute a permissive condition for the onset of insulin resistance. Our results show that constitutive expression of human COX-2 (hCOX-2) in hepatocytes protects against adiposity, inflammation, and, hence, insulin resistance induced by a high-fat diet, as demonstrated by decreased hepatic steatosis, adiposity, plasmatic and hepatic triglycerides and free fatty acids, increased adiponectin-to-leptin ratio, and decreased levels of proinflammatory cytokines, together with an enhancement of insulin sensitivity and glucose tolerance. Furthermore, hCOX-2 transgenic mice exhibited increased whole-body energy expenditure due in part by induction of thermogenesis and fatty acid oxidation. The analysis of hepatic insulin signaling revealed an increase in insulin receptor-mediated Akt phosphorylation in hCOX-2 transgenic mice. In conclusion, our results point to COX-2 as a potential therapeutic target against obesity-associated metabolic dysfunction.

  17. Abdominal obesity is a risk factor for dysexecutive function in chronic kidney disease.

    PubMed

    Zammit, Andrea R; Katz, Mindy J; Derby, Carol; Bitzer, Markus; Lipton, Richard B

    2016-12-01

    The aim of this study was to assess the influence of the metabolic syndrome and its components on dysexecutive function (DF) in individuals with and without CKD. Among 588 participants aged over 70 from the Einstein Aging Study (EAS), we defined DF as performance of 2SDs below the mean on any one test or 1.5SDs below the mean on any two of the following: Block Design, Digit Symbol Coding and the Trail-making Tests A and B. We defined CKD as an eGFR below 60 mL/min/m(2). MetS was defined according to recent guidelines from the National Cholesterol Education Program. 149 participants had CKD at cross-section, 16.1% of which also showed DF. Of the 439 participants without CKD, 12.3% displayed DF. Abdominal obesity as measured by waist circumference, was an independent risk factor for dysexecutive function in CKD (OR = 14.3, 95%CI = 2.21-91.93, p = 0.005) but not in non-CKD. None of the other MetS components were associated with DF. Results suggested that abdominal obesity, recognized as an integral part of the MetS, is a strong risk factor for DF in individuals with CKD.

  18. Chronic renin inhibition with aliskiren improves glucose tolerance, insulin sensitivity, and skeletal muscle glucose transport activity in obese Zucker rats.

    PubMed

    Marchionne, Elizabeth M; Diamond-Stanic, Maggie K; Prasonnarong, Mujalin; Henriksen, Erik J

    2012-01-01

    We have demonstrated previously that overactivity of the renin-angiotensin system (RAS) is associated with whole body and skeletal muscle insulin resistance in obese Zucker (fa/fa) rats. Moreover, this obesity-associated insulin resistance is reduced by treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor (type 1) blockers. However, it is currently unknown whether specific inhibition of renin itself, the rate-limiting step in RAS functionality, improves insulin action in obesity-associated insulin resistance. Therefore, the present study assessed the effect of chronic, selective renin inhibition using aliskiren on glucose tolerance, whole body insulin sensitivity, and insulin action on the glucose transport system in skeletal muscle of obese Zucker rats. Obese Zucker rats were treated for 21 days with either vehicle or aliskiren (50 mg/kg body wt ip). Renin inhibition was associated with a significant lowering (10%, P < 0.05) of resting systolic blood pressure and induced reductions in fasting plasma glucose (11%) and free fatty acids (46%) and homeostatic model assessment for insulin resistance (13%). Glucose tolerance (glucose area under the curve) and whole body insulin sensitivity (inverse of the glucose-insulin index) during an oral glucose tolerance test were improved by 15% and 16%, respectively, following chronic renin inhibition. Moreover, insulin-stimulated glucose transport activity in isolated soleus muscle of renin inhibitor-treated animals was increased by 36% and was associated with a 2.2-fold greater Akt Ser(473) phosphorylation. These data provide evidence that chronic selective inhibition of renin activity leads to improvements in glucose tolerance and whole body insulin sensitivity in the insulin-resistant obese Zucker rat. Importantly, chronic renin inhibition is associated with upregulation of insulin action on skeletal muscle glucose transport, and it may involve improved Akt signaling. These data support the

  19. Estrogen has opposing effects on vascular reactivity in obese, insulin-resistant male Zucker rats

    NASA Technical Reports Server (NTRS)

    Brooks-Asplund, Esther M.; Shoukas, Artin A.; Kim, Soon-Yul; Burke, Sean A.; Berkowitz, Dan E.

    2002-01-01

    We hypothesized that estradiol treatment would improve vascular dysfunction commonly associated with obesity, hyperlipidemia, and insulin resistance. A sham operation or 17beta-estradiol pellet implantation was performed in male lean and obese Zucker rats. Maximal vasoconstriction (VC) to phenylephrine (PE) and potassium chloride was exaggerated in control obese rats compared with lean rats, but estradiol significantly attenuated VC in the obese rats. Estradiol reduced the PE EC50 in all groups. This effect was cyclooxygenase independent, because preincubation with indomethacin reduced VC response to PE similarly in a subset of control and estrogen-treated lean rats. Endothelium-independent vasodilation (VD) to sodium nitroprusside was similar among groups, but endothelium-dependent VD to ACh was significantly impaired in obese compared with lean rats. Estradiol improved VD in lean and obese rats by decreasing EC50 but impaired function by decreasing maximal VD. The shift in EC50 corresponded to an upregulation in nitric oxide synthase III protein expression in the aorta of the estrogen-treated obese rats. In summary, estrogen treatment improves vascular function in male insulin-resistant, obese rats, partially via an upregulation of nitric oxide synthase III protein expression. These effects are counteracted by adverse factors, such as hyperlipidemia and, potentially, a release of an endothelium-derived contractile agent.

  20. Effects of GH on Body Composition and Cardiovascular Risk Markers in Young Men With Abdominal Obesity

    PubMed Central

    Gerweck, Anu V.; Lin, Eleanor; Landa, Melissa G.; Torriani, Martin; Schoenfeld, David A.; Hemphill, Linda C.; Miller, Karen K.

    2013-01-01

    Context: Visceral adiposity is associated with increased cardiometabolic risk and decreased GH secretion. Objective: Our objective was to determine the effects of GH administration in abdominally obese young men on body composition, including liver fat, mitochondrial function, and cardiovascular (CV) risk markers. Design and Participants: This was a 6-month, randomized, double-blind, placebo-controlled study with 62 abdominally obese men (IGF-1 below the mean, no exclusion based on GH level), 21 to 45 years of age. Main Outcome Measures: We evaluated abdominal fat depots, thigh muscle and fat (computed tomography), fat and lean mass (dual-energy x-ray absorptiometry), intramyocellular and intrahepatic lipids (proton magnetic resonance spectroscopy), mitochondrial function (dynamic phosphorous magnetic resonance spectroscopy), CV risk markers, carotid intimal-medial thickness, and endothelial function. Results: GH administration resulted in a mean IGF-1 SD score increase from −1.9 ± 0.08 to −0.2 ± 0.3 in the GH group and a decrease in visceral adipose tissue (VAT), VAT/sc adipose tissue, trunk/extremity fat, intrahepatic lipids, high-sensitivity C-reactive protein and apolipoprotein B/low-density lipoprotein vs placebo after controlling for the increase in weight observed in both groups. There were inverse associations between change in IGF-1 levels and change in VAT, VAT/sc adipose tissue, trunk fat, trunk/extremity fat, high-sensitivity C-reactive protein, and apolipoprotein B. Mitochondrial function improved in the GH group compared with placebo after controlling for change in glucose. There was no change in thigh fat, muscle mass, intramyocellular lipids, cholesterol, fibrinogen, intimal-medial thickness, or endothelial function. There was no increase in fasting glucose or hemoglobin A1c in the GH vs placebo group, although glucose during the 2-hour oral glucose tolerance test increased slightly. Conclusion: GH replacement in abdominally obese men improves

  1. Oxidative stress in severely obese persons is greater in those with insulin resistance.

    PubMed

    Tinahones, Francisco J; Murri-Pierri, Mora; Garrido-Sánchez, Lourdes; García-Almeida, Jose M; García-Serrano, Sara; García-Arnés, Juan; García-Fuentes, Eduardo

    2009-02-01

    The postprandial state seems to have a direct influence on oxidative status and insulin resistance. We determined the effect of an increase in plasma triglycerides after a high-fat meal on oxidative stress in severely obese patients with differing degrees of insulin resistance. The study was undertaken in 60 severely obese persons who received a 60-g fat overload with a commercial preparation. Measurements were made of insulin resistance, the plasma activity of various antioxidant enzymes, the total antioxidant capacity (TAC) and the plasma concentration of thiobarbituric acid reactive substances (TBARS). The patients with greater insulin resistance had a lower plasma superoxide dismutase (SOD) activity (P < 0.05) and a greater glutathione peroxidase (GSH-Px) activity (P < 0.05). The high-fat meal caused a significant reduction in SOD activity and an increase in the plasma concentration of TBARS in all the patients. Only the patients with lower insulin resistance experienced a significant increase in plasma catalase activity (2.22 +/- 1.02 vs. 2.93 +/- 1.22 nmol/min/ml, P < 0.01), remaining stable in the patients with greater insulin resistance. These latter patients had a reduction in plasma TAC (6.92 +/- 1.93 vs. 6.29 +/- 1.80 mmol/l, P < 0.01). In conclusion, our results show a close association between the degree of insulin resistance and markers of oxidative stress, both before and after a high-fat meal. The postprandial state causes an important increase in oxidative stress, especially in severely obese persons with greater insulin resistance. However, we are unable to determine from this study whether there is first an increase in oxidative stress or in insulin resistance.

  2. Abdominal adiposity and obstructive airway disease: testing insulin resistance and sleep disordered breathing mechanisms

    PubMed Central

    2012-01-01

    Background This study examined associations of abdominal adiposity with lung function, asthma symptoms and current doctor-diagnosed asthma and mediation by insulin resistance (IR) and sleep disordered breathing (SDB). Methods A random sample of 2500 households was drawn from the community of Whyalla, South Australia (The Whyalla Intergenerational Study of Health, WISH February 2008 - July 2009). Seven-hundred twenty-two randomly selected adults (≥18 years) completed clinical protocols (32.2% response rate). Lung function was measured by spirometry. Post-bronchodilator FEV1/FVC was used to measure airway obstruction and reversibility of FEV1 was calculated. Current asthma was defined by self-reported doctor-diagnosis and evidence of currently active asthma. Symptom scores for asthma (CASS) and SDB were calculated. Intra-abdominal fat (IAF) was estimated using dual-energy x-ray absorptiometry (DXA). IR was calculated from fasting glucose and insulin concentrations. Results The prevalence of current doctor-diagnosed asthma was 19.9% (95% CI 16.7 – 23.5%). The ratio of observed to expected cases given the age and sex distribution of the population was 2.4 (95%CI 2.1, 2.9). IAF was not associated with current doctor-diagnosed asthma, FEV1/FVC or FEV1 reversibility in men or women but was positively associated with CASS independent of IR and SDB in women. A 1% increase in IAF was associated with decreases of 12 mL and 20 mL in FEV1 and FVC respectively in men, and 4 mL and 7 mL respectively in women. SDB mediated 12% and 26% of these associations respectively in men but had minimal effects in women. Conclusions In this population with an excess of doctor-diagnosed asthma, IAF was not a major factor in airway obstruction or doctor-diagnosed asthma, although women with higher IAF perceived more severe asthma symptoms which did not correlate with lower FEV1. Higher IAF was significantly associated with lower FEV1 and FVC and in men SDB mechanisms may

  3. Herbal Formula HT048 Attenuates Diet-Induced Obesity by Improving Hepatic Lipid Metabolism and Insulin Resistance in Obese Rats.

    PubMed

    Lee, Yoon Hee; Jin, Bora; Lee, Sung Hyun; Song, MiKyung; Bae, HyeonHui; Min, Byung Jae; Park, Juyeon; Lee, Donghun; Kim, Hocheol

    2016-10-25

    It is well established that obesity causes a variety of chronic diseases such as cardiovascular diseases and diabetes. Despite the diligent scientific efforts to find effective ways to lower the level of obesity, the size of obese population grows continuously around the world. Here we present the results that show feeding diet containing HT048, a mixture of the extracts of Crataegus pinnatifida leaves and Citrus unshiu peel, two of the well-known traditional herbal medicines in Eastern Asia, decreases obesity in rats. We fed rats with five different diets for 10 weeks: chow diet (STD), high-fat diet (HFD), high-fat diet with 0.04% orlistat, a drug to treat obesity (HFD + Orlistat), high-fat diet with 0.2% HT048 (w/w; HFD + 0.2% HT048), and high-fat diet with 0.6% HT048 (w/w; HFD + 0.6% HT048). It was found that both body and total white adipose tissue weight of HT048 groups significantly decreased compared to those of the HFD group. Moreover, HT048 decreased serum insulin levels in HFD-fed obese rats. At the molecular level, HT048 supplementation downregulated genes involved in lipogenesis, gluconeogenesis, and adipogenesis, while the expression level of β-oxidation genes was increased. Supplementation-drug interactions are not likely as HFD and HT048-containing diet did not significantly induce genes encoding CYPs. Collectively, this study suggests that HT048 taken as dietary supplement helps to decrease obesity and insulin resistance in HFD-fed obese rats.

  4. Aerobic exercise training-induced decrease in plasma visfatin and insulin resistance in obese female adolescents.

    PubMed

    Lee, Kyu-Jin; Shin, Yun-A; Lee, Kyoung-Young; Jun, Tae-Won; Song, Wook

    2010-08-01

    The purpose of this study was to assess differences in the levels of plasma visfatin among female adolescents and changes in plasma visfatin and insulin resistance in obese female adolescents after 12 wk of aerobic exercise training. Twenty normal-weight female students (body-mass index [BMI] < 22.9 kg/m² and body fat ≤ 29.9) and 18 obese female students (BMI ≥ 25 kg/ m² and body fat ≥ 30%) participated in this study. Eleven obese students were assigned to an exercise group and completed a 12-wk aerobic exercise-training program that included four 40- to 50-min sessions per wk with an energy expenditure of 300-400 kcal/d. Seven obese students were assigned to a control group that received no exercise sessions or dietary restriction. The plasma visfatin levels of obese female adolescents were significantly higher (p < .05) than those of the normal-weight female adolescents. The plasma visfatin levels (294.00 ± 124.74 ng/ml to 185.55 ± 67.30 ng/ml, p < .01) and insulin resistance (p < .05) were significantly reduced after 12 wk of aerobic exercise. The results suggest that aerobic exercise resulting in an energy expenditure of 1,200-1,600 kcal/wk for 12 wk decreases plasma visfatin and insulin resistance in obese female adolescents.

  5. [Contribution of leptin in the development of insulin resistance in pregnant women with obesity].

    PubMed

    Tarasenko, K

    2014-03-01

    The aim of the present study was to investigate contribution of leptin in the development of insulin resistance in obese pregnant women depending on the obesity class as well as its effect on the progression of pregnancy. 36 pregnant women of I and II obesity classes and 21 pregnant women with normal body mass participated in the study. Concentrations of insulin, leptin and C-reactive protein in blood serum were measured with immunoenzymatic assays. Insulin resistance (IR) was determined with the Caro index. Contribution of leptin to development of IR was assessed with the ratio "leptin/Caro index". An increase of leptin concentration in blood serum was found in pregnant women with obesity compared to healthy controls. Moreover, the ratio "leptin/Caro index" increased with IR progression and reached maximum in the group with obesity class II, where it was 5.8 times higher than in the control group. An increased frequency of gestoses and placentary dysfunction were manifestations of weakening of adaptive mechanisms of the organism associated with the IR progression and increased role of leptin in its development. Therefore, activation of adipocyte function through the increased leptin secretion and increased ratio "leptin/Caro index" reflects the important role of leptin in pathogenesis of IR in pregnant women with obesity.

  6. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance.

    PubMed

    Vandanmagsar, Bolormaa; Youm, Yun-Hee; Ravussin, Anthony; Galgani, Jose E; Stadler, Krisztian; Mynatt, Randall L; Ravussin, Eric; Stephens, Jacqueline M; Dixit, Vishwa Deep

    2011-02-01

    The emergence of chronic inflammation during obesity in the absence of overt infection or well-defined autoimmune processes is a puzzling phenomenon. The Nod-like receptor (NLR) family of innate immune cell sensors, such as the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (Nlrp3, but also known as Nalp3 or cryopyrin) inflammasome are implicated in recognizing certain nonmicrobial originated 'danger signals' leading to caspase-1 activation and subsequent interleukin-1β (IL-1β) and IL-18 secretion. We show that calorie restriction and exercise-mediated weight loss in obese individuals with type 2 diabetes is associated with a reduction in adipose tissue expression of Nlrp3 as well as with decreased inflammation and improved insulin sensitivity. We further found that the Nlrp3 inflammasome senses lipotoxicity-associated increases in intracellular ceramide to induce caspase-1 cleavage in macrophages and adipose tissue. Ablation of Nlrp3 in mice prevents obesity-induced inflammasome activation in fat depots and liver as well as enhances insulin signaling. Furthermore, elimination of Nlrp3 in obese mice reduces IL-18 and adipose tissue interferon-γ (IFN-γ) expression, increases naive T cell numbers and reduces effector T cell numbers in adipose tissue. Collectively, these data establish that the Nlrp3 inflammasome senses obesity-associated danger signals and contributes to obesity-induced inflammation and insulin resistance.

  7. Potential Epigenetic Biomarkers of Obesity Related Insulin Resistance in Human Whole-blood.

    PubMed

    Day, Samantha E; Coletta, Richard L; Kim, Joon Young; Garcia, Luis A; Campbell, Latoya E; Benjamin, Tonya R; Roust, Lori R; De Filippis, Elena A; Mandarino, Lawrence J; Coletta, Dawn K

    2017-01-20

    Obesity can increase the risk of complex metabolic diseases, including insulin resistance. Moreover, obesity can be caused by environmental and genetic factors. However, the epigenetic mechanisms of obesity are not well defined. Therefore, the identification of novel epigenetic biomarkers of obesity allows for a more complete understanding of the disease and its underlying insulin resistance. The aim of our study was to identify DNA methylation changes in whole-blood that were strongly associated with obesity and insulin resistance. Whole-blood was obtained from lean (n = 10; BMI = 23.6 ± 0.7 kg/m(2)) and obese (n = 10; BMI = 34.4 ± 1.3 kg/m(2)) participants in combination with euglycemic hyperinsulinemic clamps to assess insulin sensitivity. We performed reduced representation bisulfite sequencing on genomic DNA isolated from the blood. We identified 49 differentially methylated cytosines (DMCs; q<0.05) that were altered in obese compared to lean participants. We identified two sites (Chr.21:46,957,981 and Chr.21:46,957,915) in the 5' untranslated region of solute carrier family 19 member 1 (SLC19A1) with decreased in methylation in obese participants (lean 0.73 ± 0.11 vs. obese 0.09 ± 0.05; lean 0.68 ± 0.10 vs. obese 0.09 ± 0.05, respectively). These two DMCs identified by obesity were also significantly predicted by insulin sensitivity (r = 0.68, P = 0.003; r = 0.66; P = 0.004). In addition, we performed a differentially methylated region (DMR) analysis and demonstrated a decrease in methylation of Chr.21:46,957,915-46,958,001 in SLC19A1 of -34.9% (70.4% lean vs. 35.5% obese). The decrease in whole-blood SLC19A1 methylation in our obese participants was similar to the change observed in skeletal muscle (Chr.21:46,957,981, lean 0.70 ± 0.09 vs. obese 0.31 ± 0.11 and Chr.21:46,957,915, lean 0.72 ± 0.11 vs. obese 0.31 ± 0.13). Pyrosequencing analysis further demonstrated a decrease in methylation at Chr.21:46,957,915 in both whole-blood (lean 0.71 ± 0

  8. Recent advances in the relationship between obesity, inflammation, and insulin resistance.

    PubMed

    Bastard, Jean-Philippe; Maachi, Mustapha; Lagathu, Claire; Kim, Min Ji; Caron, Martine; Vidal, Hubert; Capeau, Jacqueline; Feve, Bruno

    2006-03-01

    It now appears that, in most obese patients, obesity is associated with a low-grade inflammation of white adipose tissue (WAT) resulting from chronic activation of the innate immune system and which can subsequently lead to insulin resistance, impaired glucose tolerance and even diabetes. WAT is the physiological site of energy storage as lipids. In addition, it has been more recently recognized as an active participant in numerous physiological and pathophysiological processes. In obesity, WAT is characterized by an increased production and secretion of a wide range of inflammatory molecules including TNF-alpha and interleukin-6 (IL-6), which may have local effects on WAT physiology but also systemic effects on other organs. Recent data indicate that obese WAT is infiltrated by macrophages, which may be a major source of locally-produced pro-inflammatory cytokines. Interestingly, weight loss is associated with a reduction in the macrophage infiltration of WAT and an improvement of the inflammatory profile of gene expression. Several factors derived not only from adipocytes but also from infiltrated macrophages probably contribute to the pathogenesis of insulin resistance. Most of them are overproduced during obesity, including leptin, TNF-alpha, IL-6 and resistin. Conversely, expression and plasma levels of adiponectin, an insulin-sensitising effector, are down-regulated during obesity. Leptin could modulate TNF-alpha production and macrophage activation. TNF-alpha is overproduced in adipose tissue of several rodent models of obesity and has an important role in the pathogenesis of insulin resistance in these species. However, its actual involvement in glucose metabolism disorders in humans remains controversial. IL-6 production by human adipose tissue increases during obesity. It may induce hepatic CRP synthesis and may promote the onset of cardiovascular complications. Both TNF-alpha and IL-6 can alter insulin sensitivity by triggering different key steps in the

  9. Vitamin D status is not related to insulin resistance in different phenotypes of moderate obesity.

    PubMed

    Al Masri, Manal; Romain, Ahmed Jerome; Boegner, Catherine; Maimoun, Laurent; Mariano-Goulart, Denis; Attalin, Vincent; Leprieur, Elodie; Picandet, Marion; Avignon, Antoine; Sultan, Ariane

    2017-01-03

    Low plasma 25-hydroxy-vitamin D (25OHD) and high levels of parathyroid hormone (PTH) are associated with obesity and could play a role in the occurrence of complications such as insulin resistance. The objective of the study was to evaluate whether the relationship between 25OHD status and phosphocalcic parameters differs between metabolically healthy obese (MHO) and insulin-resistant obese (IRO). This cross-sectional study included 158 consecutive adults (121 females) with obesity (body mass index (BMI) 35.15 ± 2.8 kg/m(2)), aged 43.21 ± 13.6 years. Serum 25OHD, calcemia, phosphatemia, PTH, plasma lipids, fasting plasma glucose, insulin levels, and body composition were measured. Participants were classified as MHO (n = 65) or IRO (n = 93) based on homeostatic model assessment insulin-resistance value. IRO patients had a higher BMI (p = 0.001), waist circumference (p = 0.03), and trunk fat mass (p = 0.007) than MHO patients. Mean HbA1c (p = 0.03), triglycerides (p = 0.02), and hsCRP (p = 0.04) plasmatic levels were increased in the IRO group. No between-group difference was found on 25OHD, PTH, calcium, or phosphorus plasmatic levels. Only age-predicted 25OHD levels were identified among IRO participants, whereas no factors were identified in MHO. No predictive factors of PTH plasmatic level were identified in the IRO and MHO groups. Although MHO and IRO patients have different metabolic profiles, we did not detect any difference regarding either 25OHD or PTH. Insulin resistance was not a predictive factor of vitamin D status. Our results confirm the absence of link between vitamin D status and insulin resistance in moderate obesity.

  10. Human muscle fiber type-specific insulin signaling: impact of obesity and type 2 diabetes.

    PubMed

    Albers, Peter H; Pedersen, Andreas J T; Birk, Jesper B; Kristensen, Dorte E; Vind, Birgitte F; Baba, Otto; Nøhr, Jane; Højlund, Kurt; Wojtaszewski, Jørgen F P

    2015-02-01

    Skeletal muscle is a heterogeneous tissue composed of different fiber types. Studies suggest that insulin-mediated glucose metabolism is different between muscle fiber types. We hypothesized that differences are due to fiber type-specific expression/regulation of insulin signaling elements and/or metabolic enzymes. Pools of type I and II fibers were prepared from biopsies of the vastus lateralis muscles from lean, obese, and type 2 diabetic subjects before and after a hyperinsulinemic-euglycemic clamp. Type I fibers compared with type II fibers have higher protein levels of the insulin receptor, GLUT4, hexokinase II, glycogen synthase (GS), and pyruvate dehydrogenase-E1α (PDH-E1α) and a lower protein content of Akt2, TBC1 domain family member 4 (TBC1D4), and TBC1D1. In type I fibers compared with type II fibers, the phosphorylation response to insulin was similar (TBC1D4, TBC1D1, and GS) or decreased (Akt and PDH-E1α). Phosphorylation responses to insulin adjusted for protein level were not different between fiber types. Independently of fiber type, insulin signaling was similar (TBC1D1, GS, and PDH-E1α) or decreased (Akt and TBC1D4) in muscle from patients with type 2 diabetes compared with lean and obese subjects. We conclude that human type I muscle fibers compared with type II fibers have a higher glucose-handling capacity but a similar sensitivity for phosphoregulation by insulin.

  11. The Impact of Insulin Resistance and Inflammation on the Association Between Sarcopenic Obesity and Physical Functioning

    PubMed Central

    Levine, Morgan E.; Crimmins, Eileen M.

    2012-01-01

    Age associated increases in visceral adiposity and decreases in muscle mass (sarcopenia) have been shown to contribute to disability in late life. Furthermore, there is evidence that obesity-related physiological states, such as insulin resistance and systemic inflammation, may exacerbate physical functioning problems. Both conditions have been shown to prompt hypercatabolism and impair the anabolic effect of muscles, ultimately stimulating protein breakdown and suppressing muscle synthesis. This cross-sectional study investigates whether insulin resistance and inflammation partially account for the associations between decreased physical functioning and sarcopenic obesity. Subjects include 2,287 males and females aged 60 and older without diagnosed diabetes from the National Health and Nutrition Examination Survey (NHANES 1999–2004). Body composition measurements indicating waist circumference and appendicular skeletal muscle mass, measured by dual-energy X-ray absorptiometry (DXA), were used to construct four body composition categories—healthy, sarcopenic nonobese, nonsarcopenic obese, and sarcopenic obese. Physical functioning was measured using self-reports of difficulty performing six activities. The homeostasis model assessment (IRHOMA) was used to measure insulin resistance, while inflammatory state was assessed through measurement of serum C-reactive protein (CRP). Modified Poisson regression models were used to examine the association between physical functioning and body composition, and to evaluate whether differences in insulin resistance or inflammation partially explained this relationship. In the analysis, we controlled for possible confounders such as age, education, sex, height, and race/ethnicity. Findings suggest that physical functioning problems are increased in those with sarcopenic obesity, sarcopenic nonobesity and nonsarcopenic obesity. Furthermore, these associations may be influenced by differences in insulin resistance among

  12. Obesity, insulin resistance and diabetes--a worldwide epidemic.

    PubMed

    Seidell, J C

    2000-03-01

    Obesity is now commonly defined in adults as a BMI > 30 kg/m2. The prevalence of obesity in established market economies (Europe, USA, Canada, Australia, etc.) varies greatly, but a weighed estimate suggests an average prevalence in the order of 15-20%. The prevalence in these countries generally shows increasing trends over time. Obesity is also relatively common in Latin America, but much less so in sub-Saharan Africa and Asia where the majority of the world population lives. Nevertheless obesity rates are increasing there as well and, more importantly, rates of diabetes are increasing even more quickly, particularly in Asian countries. The risks of type 2 diabetes mellitus in these countries tend to increase sharply at levels of BMI generally classified as acceptable in European and North American white people. There have been suggestions to adopt specific classifications of obesity in Asians (e.g. BMI 23 for overweight and 25 or 27 kg/m2 for obesity) and this will greatly affect the prevalence estimates of obesity worldwide (currently at about 250 million people). Particularly for health promotion purposes BMI may be replaced by a classification based on waist circumference, but also specific classifications for different ethnic groups may be necessary. The number of diabetics has been projected to increase from 135 million in 1995 to 300 million in 2025. Much of this increase will be seen in Asia. In summary, both obesity and type 2 diabetes are common consequences of changing lifestyles (increased sedentary lifestyles and increased energy density of diets). Both are potentially preventable through lifestyle modification on a population level, but this requires a coherent and multifaceted strategy. Such strategies are not developed or implemented. These developments point toward the great urgency to develop global and national plans for adequate prevention and management of obesity and type 2 diabetes mellitus.

  13. Insulin sensitivity and first-phase insulin secretion in obese Chinese with hyperglycemia in 30 and/or 60 min during glucose tolerance tests.

    PubMed

    Hong, Jie; Zhang, Yi-Fei; Gu, Wei-qiong; Zhang, Yu-wen; Su, Yu-xia; Chi, Zhen-ni; Wang, Wei-qing; Li, Xiao-ying; Ning, Guang

    2008-01-01

    The purpose of this study was to investigate insulin sensitivity and first-phase insulin secretion in obesity with hyperglycemia in 30 and/or 60 min during oral glucose tolerance (OGTT, glucose > or = 11.1 mmol/l, post-loading hyperglycemia, PLH) in Chinese population. A total of 196 nondiabetic subjects were included in the present study, among them 99 had normal glucose tolerance (NGT, subdivided into 32 lean NGT and 67 obese NGT), 74 had obesity with impaired glucose tolerance (IGT) and 23 had obesity with PLH. A standard 75-g oral glucose tolerance test was performed after fasting and at 30 min, 1, 2 and 3 h. Insulin sensitivity index (S(I)) was assessed by the Bergman's minimal model method with frequently sampled intravenous glucose tolerance test (FSIGTT), insulin secretion was determined by acute insulin response to glucose (AIRg). The disposition index (DI), the product of AIRg and S(I) was used to determine whether AIRg was adequate to compensate for insulin resistance. S(I) was significantly equally lower in three obese subgroups. AIRg was significantly increased in obese NGT as compared with lean NGT controls, and reduced to the same extent in IGT and PLH subjects. There was no significant difference among lean NGT, IGT and PLH subjects. DI value was reduced from obese NGT individuals, IGT and PLH subjects had a similar lower level of DI. In conclusion, our present results demonstrated that the pathophysiological basis of obese subjects with PLH were clearly insulin resistance and defective in first-phase insulin secretion as that in IGT subjects in Chinese population.

  14. Population-attributable fraction of hypertension associated with obesity, abdominal obesity, and the joint effect of both in the Central Provinces of Iran.

    PubMed

    Mohammadi, Masoud; Mirzaei, Masoud

    2017-03-01

    The prevalence of obesity has been increasing in Iran over the past decade. This study aimed to determine the population-attributable fraction (PAF) of hypertension associated with obesity, abdominal obesity, and the joint effect of both in the central provinces of Iran. Prevalence of hypertension was extracted from the Iranian Ministry of Health Non-Communicable Disease Risk Factor InfoBase 2009. Measure of association between obesity and hypertension was extracted from Tehran Lipid and Glucose Study, for males and females, in order to calculate the PAF of hypertension associated with obesity. Age standardization of the reported prevalence of obesity was done using the World Health Organization method. The PAF of hypertension associated with the joint effect of obesity and abdominal obesity in females was highest in Semnan Province: 22.7 [95% confidence interval (CI): 4.2-35.6], followed by Qom 21.09 (95% CI: 3.7-33.1), and Yazd 20.3 (95% CI: 3.5-32.1). In males, the highest PAF was observed in Qom Province 31.07 (95% CI: 16.7-41.1), followed by Semnan 29.6 (95% CI: 15.9-39.3), Qazvin 25.9 (95% CI: 13.7-34.5), Tehran 24.2 (95% CI: 12.7-32.3), and Isfahan 20.4 (95% CI: 3.5-27.4). Prevalence of hypertension is higher in more developed provinces. PAFs suggest that a sizable share of hypertension in these provinces is associated with obesity. It is recommended that health promotion programs focus on obesity in the provinces with a higher share of hypertension due to obesity.

  15. Hormones and Obesity: Changes in Insulin and Growth Hormone Secretion Following Surgically Induced Weight Loss

    PubMed Central

    Crockford, P. M.; Salmon, P. A.

    1970-01-01

    Ten obese patients were subjected to insulin tolerance tests (0.2 unit per kg. regular insulin intravenously) and/or treadmill exercise tolerance testing (2.6 m.p.h. at 11° angulation) before and after surgically induced weight reduction. Immunoreactive growth hormone (IRGH) responses returned to normal with weight reduction in all but one—a grossly obese woman studied relatively early in the postoperative period when still far from the ideal body weight. Five of these patients and two additional subjects had intravenous glucose tolerance tests (0.5 g. per kg.) before and after weight reduction. In all, there was a significant diminution in immunoreactive insulin (IRI) values, accompained by little or no change in the glucose disappearance rate (KG) and a significant improvement in insulin effectiveness as indicated by the calculated “insulinogenic index”. It was concluded that the abnormalities in IRGH and IRI secretion, as well as the insulin resistance in obesity, are probably secondary and not of primary importance in the etiology of this disorder. PMID:5430052

  16. Overexpression of c-myc in the liver prevents obesity and insulin resistance.

    PubMed

    Riu, Efren; Ferre, Tura; Hidalgo, Antonio; Mas, Alex; Franckhauser, Sylvie; Otaegui, Pedro; Bosch, Fatima

    2003-09-01

    Alterations in hepatic glucose metabolism play a key role in the development of the hyperglycemia observed in type 2 diabetes. Because the transcription factor c-Myc induces hepatic glucose uptake and utilization and blocks gluconeogenesis, we examined whether hepatic overexpression of c-myc counteracts the insulin resistance induced by a high-fat diet. After 3 months on this diet, control mice became obese, hyperglycemic, and hyperinsulinemic, indicating that they had developed insulin resistance. In contrast, transgenic mice remained lean and showed improved glucose disposal and normal levels of blood glucose and insulin, indicating that they had developed neither obesity nor insulin resistance. These findings were concomitant with normalization of hepatic glucokinase and pyruvate kinase gene expression and enzyme activity, which led to normalization of intrahepatic glucose-6-phosphate and glycogen content. In the liver of control mice fed a high-fat diet, the expression of genes encoding proteins that control energy metabolism, such as sterol receptor element binding protein 1-c, peroxisome proliferator activated receptor alpha, and uncoupling protein-2, was altered. In contrast, in the liver of transgenic mice fed a high-fat diet, the expression of these genes was normal. These results suggest that c-myc overexpression counteracted the obesity and insulin resistance induced by a high-fat diet by modulating the expression of genes that regulate hepatic metabolism.

  17. [Adiponectin, insulin and glucose concentrations in overweight and obese subjects after a complex carbohydrates (fiber) diet].

    PubMed

    González Rodríguez, Dora Cristina; Solano R, Liseti; González Martínez, Julio César

    2009-09-01

    Adiponectin one of the cytokines secreted by the adipose tissue that regulates the energetic metabolism through glucose and insulin interactions, stimulates the oxidation of fatty acids, reduces the plasmatic triglycerides and improves glucose metabolism by increasing insulin sensibility. Serum concentrations of adiponectin, insulin and glucose were assessed in order to establish association to weight loss after a dietary regime based on consumption of complex carbohydrates (fiber) during six weeks. Overweight and obese subjects (n=56) were studied by anthropometry. Adiponectin and insulin were measured by ELISA and glucose by Colorimetry. Data was analyzed by non parametric tests to compare independent or related samples. 12 men and 44 women, aged 20 to 55 years, 17 overweight and 39 obese were assessed. Adiponectin concentration was significantly low at basal determination in all the subjects (4,47 +/- 1,64); being higher in women (4,62 +/- 1,57 vs 3,93 +/- 1,86 microU/mL in men), while glucose and insulin values were at normal range (82,46 +/-26,51 mg/dL and 14,12 +/- 10,15 microU/mL) respectively with no significant differences for sex. Overweight subjects had significantly higher adiponectin concentrations than obese participants, at all measurements. Dietary regime promoted significant increase in adiponectin concentration at second and sixth week, with a negative correlation to body mass index and gender as they lost body weight.

  18. The Effect of Zinc Supplementation on Insulin Resistance in Obese Subjects: a Systematic Review.

    PubMed

    Cruz, Kyria Jayanne Clímaco; Morais, Jennifer Beatriz Silva; de Oliveira, Ana Raquel Soares; Severo, Juliana Soares; Marreiro, Dilina do Nascimento

    2017-04-01

    Obesity is a chronic disease characterized by excessive accumulation of body fat and the presence of metabolic disorders such as insulin resistance. In this sense, zinc is an important nutrient that stimulates insulin secretion and increases sensitivity to insulin. The aim of this study was to investigate the effect of zinc supplementation on insulin resistance in obese subjects through a systematic review of the available clinical trials. The search for articles was conducted using the PubMed, SciVerse Scopus, SciVerse ScienceDirect, and Cochrane databases, on May 25, 2016, by two authors independently. The recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed in the conduct of this review. The Cochrane Collaboration tool was used to assess the risk of bias of the trials included in this review. After screening of the articles, six clinical trials were included in this systematic review. The scientific evidence presented in this systematic review shows that zinc supplementation improves insulin resistance in obese individuals of both sexes.

  19. Metabolic consequences of obesity and insulin resistance in polycystic ovary syndrome: diagnostic and methodological challenges.

    PubMed

    Jeanes, Yvonne M; Reeves, Sue

    2017-02-22

    Women with polycystic ovary syndrome (PCOS) have a considerable risk of metabolic dysfunction. This review aims to present contemporary knowledge on obesity, insulin resistance and PCOS with emphasis on the diagnostic and methodological challenges encountered in research and clinical practice. Variable diagnostic criteria for PCOS and associated phenotypes are frequently published. Targeted searches were conducted to identify all available data concerning the association of obesity and insulin resistance with PCOS up to September 2016. Articles were considered if they were peer reviewed, in English and included women with PCOS. Obesity is more prevalent in women with PCOS, but studies rarely reported accurate assessments of adiposity, nor split the study population by PCOS phenotypes. Many women with PCOS have insulin resistance, though there is considerable variation reported in part due to not distinguishing subgroups known to have an impact on insulin resistance as well as limited methodology to measure insulin resistance. Inflammatory markers are positively correlated with androgen levels, but detailed interactions need to be identified. Weight management is the primary therapy; specific advice to reduce the glycaemic load of the diet and reduce the intake of pro-inflammatory SFA and advanced glycation endproducts have provided promising results. It is important that women with PCOS are educated about their increased risk of metabolic complications in order to make timely and appropriate lifestyle modifications. Furthermore, well-designed robust studies are needed to evaluate the mechanisms behind the improvements observed with dietary interventions.

  20. Dietary taurine and nutrients intake and anthropometric and body composition data by abdominal obesity in Korean male college students.

    PubMed

    Sung, Min Jung; Chang, Kyung Ja

    2009-01-01

    The purpose of this study was to investigate the relationship between abdominal obesity and dietary taurine intake, nutrient intake, anthropometric data and body composition in Korean male college students. One hundred seventy four subjects were divided into 2 groups based on abdominal obesity as estimated by waist circumference (cm) (Lee et al. 2006): normal group (waist circumference (cm): < 90 cm, n = 141), obese group (waist circumference (cm): > or = 90 cm, n = 33). A three day-recall method was used to assess diet (2 weekdays and 1 weekend). Anthropometric data and body composition were measured with Inbody 3.0 (Bioelectrical Impedance Fatness Analyzer). Average dietary intake of taurine in the normal and obese groups was 123.1 +/- 78.8 mg/day and 128.4 +/- 79.6 mg/day, respectively. There was no significant difference in dietary taurine and nutrient intake between the normal and obese groups. However, data of anthropometric measurements and body composition in the obese group were significantly elevated compared to those of the normal group. In the normal group, dietary taurine intake was positively correlated with nutrient intake (p < 0.01), the exception being the intake of plant lipid and of animal calcium. In the obese group, dietary taurine intake was positively correlated with the intake of energy foods and of animal lipid (p < 0.05). There were positive correlations between dietary taurine intake, weight and hip circumference (p < 0.05) in the normal group. However, there was no significant correlation between dietary taurine intake and anthropometric and body composition data in the obese group. Therefore, the data suggest that further study is warranted to examine the relationship between dietary taurine intake and abdominal obesity.

  1. Vitamin B12 in obese adolescents with clinical features of insulin resistance.

    PubMed

    Ho, Mandy; Halim, Jocelyn H; Gow, Megan L; El-Haddad, Nouhad; Marzulli, Teresa; Baur, Louise A; Cowell, Chris T; Garnett, Sarah P

    2014-12-04

    Emerging evidence indicates an association between obesity, metformin use and reduced vitamin B12 status, which can have serious hematologic, neurologic and psychiatric consequences. This study aimed to examine B12 status in obese adolescents with pre-diabetes and/or clinical features of insulin resistance. Serum B12 was measured using chemiluminescence immunoassay in 103 (43 male, 60 female) obese (mean body mass index (BMI) z-score ± SD (2.36 ± 0.29)), adolescents aged 10 to 17 years, median (range) insulin sensitivity index of 1.27 (0.27 to 3.38) and 13.6% had pre-diabetes. Low B12 (<148 pmol/L) was identified in eight (7.8%) and borderline status (148 to 221 pmol/L) in an additional 25 (24.3%) adolescents. Adolescents with borderline B12 concentrations had higher BMI z-scores compared to those with normal concentrations (2.50 ± 0.22 vs. 2.32 ± 0.30, p = 0.008) or those with low B12 concentration (2.50 ± 0.22 vs. 2.27 ± 0.226, p = 0.041). In conclusion, nearly a third of obese adolescents with clinical insulin resistance had a low or borderline serum B12 status. Therefore, further investigations are warranted to explore the cause and the impact of low B12 status in obese pediatric populations.

  2. Is salivary gland function altered in noninsulin-dependent diabetes mellitus and obesity-insulin resistance?

    PubMed

    Ittichaicharoen, Jitjiroj; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2016-04-01

    Salivary gland dysfunction in several systemic diseases has been shown to decrease the quality of life in patients. In non-insulin dependent diabetes mellitus (NIDDM), inadequate salivary gland function has been evidenced to closely associate with this abnormal glycemic control condition. Although several studies demonstrated that NIDDM has a positive correlation with impaired salivary gland function, including decreased salivary flow rate, some studies demonstrated contradictory findings. Moreover, the changes of the salivary gland function in pre-diabetic stage known as insulin resistance are still unclear. The aim of this review is to comprehensively summarize the current evidence from in vitro, in vivo and clinical studies regarding the relationship between NIDDM and salivary gland function, as well as the correlation between obesity and salivary gland function. Consistent findings as well as controversial reports and the mechanistic insights regarding the effect of NIDDM and obesity-insulin resistance on salivary gland function are also presented and discussed.

  3. A Twenty-First Century Cancer Epidemic Caused by Obesity: The Involvement of Insulin, Diabetes, and Insulin-Like Growth Factors

    PubMed Central

    Westley, Rosalyne L.; May, Felicity E. B.

    2013-01-01

    Obesity has reached epidemic proportions in the developed world. The progression from obesity to diabetes mellitus type 2, via metabolic syndrome, is recognised, and the significant associated increase in the risk of major human cancers acknowledged. We review the molecular basis of the involvement of morbidly high concentrations of endogenous or therapeutic insulin and of insulin-like growth factors in the progression from obesity to diabetes and finally to cancer. Epidemiological and biochemical studies establish the role of insulin and hyperinsulinaemia in cancer risk and progression. Insulin-like growth factors, IGF-1 and IGF-2, secreted by visceral or mammary adipose tissue have significant paracrine and endocrine effects. These effects can be exacerbated by increased steroid hormone production. Structural studies elucidate how each of the three ligands, insulin, IGF-1, and IGF-2, interacts differently with isoforms A and B of the insulin receptor and with type I IGF receptor and explain how these protagonists contribute to diabetes-associated cancer. The above should inform appropriate treatment of cancers that arise in obese individuals and in those with diabetes mellitus type 2. Novel drugs that target the insulin and insulin-like growth factor signal transduction pathways are in clinical trial and should be effective if appropriate biomarker-informed patient stratification is implemented. PMID:23983688

  4. Acanthosis Nigricans as a Clinical Predictor of Insulin Resistance in Obese Children

    PubMed Central

    Koh, Young Kwon; Lee, Jae Hee; Kim, Eun Young

    2016-01-01

    Purpose This study aimed to evaluate the utility of acanthosis nigricans (AN) severity as an index for predicting insulin resistance in obese children. Methods The subjects comprised 74 obese pediatric patients who attended the Department of Pediatrics at Chosun University Hospital between January 2013 and March 2016. Waist circumference; body mass index; blood pressure; fasting glucose and fasting insulin levels; lipid profile; aspartate transaminase, alanine transaminase, glycated hemoglobin, C-peptide, and uric acid levels; and homeostatic model assessment insulin resistance (HOMA-IR) and quantitative insulin check sensitivity index (QUICKI) scores were compared between subjects with AN and those without AN. Receiver operating characteristic curves were used to investigate the utility of the AN score in predicting insulin resistance. HOMA-IR and QUICKI were compared according to AN severity. Results The With AN group had higher fasting insulin levels (24.1±21.0 mU/L vs. 9.8±3.6 mU/L, p<0.001) and HOMA-IR score (5.74±4.71 vs. 2.14±0.86, p<0.001) than the Without AN group. The AN score used to predict insulin resistance was 3 points or more (sensitivity 56.8%, specificity 83.9%). HOMA-IR scores increased with AN severity, from the Without AN group (mean, 2.15; 95% confidence interval [CI], 1.72-2.57) to the Mild AN (mean, 4.15; 95% CI, 3.04-5.25) and Severe AN groups (mean, 7.22; 95% CI, 5.08-9.35; p<0.001). Conclusion Insulin resistance worsens with increasing AN severity, and patients with Severe AN (AN score ≥3) are at increased risk of insulin resistance. PMID:28090470

  5. Continuous glucose monitoring, oral glucose tolerance, and insulin - glucose parameters in adolescents with simple obesity.

    PubMed

    El Awwa, A; Soliman, A; Al-Ali, M; Yassin, M; De Sanctis, V

    2012-09-01

    In obese adolescents pancreatic beta-cells may not be able to cope with insulin resistance leading to hyperglycemia and type2 diabetes (T2DM To assess oral glucose tolerance, 72-h continuous blood glucose concentrations (CGM) and calculate homeostatic model assessment (HOMA), and the quantitative insulin sensitivity check index (QUICKI) in 13 adolescents with simple obesity (BMI SDS=4 ± 1.06). OGTT performed in 13 obese adolescents (13.47 ± 3 years) revealed 3 cases (23%) with impaired fasting glucose (IFG: fasting glucose >5.6 mmol/L), 4 cases (30%) with impaired glucose tolerance (IGT: 2h blood glucose >7.8 <11.1 mmol/L), and none with diabetes. Using the continuous glucose monitoring system ( CGMS), IFG was detected in 4 cases, the maximum serum blood glucose (BG : 2h or more after meal) was >7.8 and <11.1 mmol/L (IGT) in 9 children (69%) and >11.1 mmol/L (diabetes) in one case (7.6%). Five cases had a minimum BG recorded of <2.7 mmol/L (hypoglycemia). No glycemic abnormality was detected using HbA1C (5.7 ± 0.3%). 11/13 patients had HOMA values >2.6 and QUICKI values <0.35 denoting insulin resistance. Beta cell mass percent (B %) = 200 ± 94.8% and insulin sensitivity values (IS)=50.4 ± 45.5% denoted insulin resistance with hyper-insulinaemia and preserved beta cell mass. In obese adolescents, CGMS is superior to OGTT and HbA1C in detecting glycemic abnormalities, which appears to be secondary to insulin resistance.

  6. Steroidogenic acute regulatory protein (StAR) overexpression reduces inflammation and insulin resistance in obese mice.

    PubMed

    Qiu, Yanyan; Sui, Xianxian; Cao, Shengxuan; Li, Xiaobo; Ning, Yanxia; Wang, Songmei; Yin, Lianhua; Zhi, Xiuling

    2017-04-12

    Steroidogenic acute regulatory protein (StAR), a mitochondrial cholesterol delivery protein, plays a beneficial role in hyperlipidemia, NAFLD and endothelial inflammation. Elevated circulating fatty acids and low grade inflammation are known as key risk factors of insulin resistance and type 2 diabetes. In the present study, C57BL/6J mice were fed with a HFD and infected with recombinant adenovirus expressing StAR by tail-vein injection. Intraperitoneal glucose/insulin tolerance test was performed to assess the insulin sensitivity. Morphological analysis and intramuscular lipid determination were used to illustrate the adipose hypertrophy and ectopic fat accumulation in skeletal muscle. The levels of inflammatory factor and nitric oxide were determined by ELISA and classic Griess reagent methods respectively. The fatty acids composition was analysis using gas chromatography -mass spectrometry (GC-MS). The expression of genes associated with inflammation and insulin resistance were determined by Western blotting and qPCR to elucidate the underlying mechanism.We demonstrated that StAR overexpression ameliorated insulin resistance and systemic inflammatory response with the reduction of adipose hypertrophy and intramuscular lipid in HFD fed mice. In addition, StAR overexpression increased serum unsaturated fatty acids and PPARγ expression in muscle and adipose tissue of obese mice. In conclusion, StAR may activate PPARγ by increasing unsaturated fatty acids, which leads to a protective role in systemic inflammation and insulin resistance in obese mice. This article is protected by copyright. All rights reserved.

  7. G protein–coupled receptor 21 deletion improves insulin sensitivity in diet-induced obese mice

    PubMed Central

    Osborn, Olivia; Oh, Da Young; McNelis, Joanne; Sanchez-Alavez, Manuel; Talukdar, Saswata; Lu, Min; Li, PingPing; Thiede, Lucinda; Morinaga, Hidetaka; Kim, Jane J.; Heinrichsdorff, Jan; Nalbandian, Sarah; Ofrecio, Jachelle M.; Scadeng, Miriam; Schenk, Simon; Hadcock, John; Bartfai, Tamas; Olefsky, Jerrold M.

    2012-01-01

    Obesity-induced inflammation is a key component of systemic insulin resistance, which is a hallmark of type 2 diabetes. A major driver of this inflammation/insulin resistance syndrome is the accumulation of proinflammatory macrophages in adipose tissue and liver. We found that the orphan GPCR Gpr21 was highly expressed in the hypothalamus and macrophages of mice and that whole-body KO of this receptor led to a robust improvement in glucose tolerance and systemic insulin sensitivity and a modest lean phenotype. The improvement in insulin sensitivity in the high-fat diet–fed (HFD-fed) Gpr21 KO mouse was traced to a marked reduction in tissue inflammation caused by decreased chemotaxis of Gpr21 KO macrophages into adipose tissue and liver. Furthermore, mice lacking macrophage expression of Gpr21 were protected from HFD-induced inflammation and displayed improved insulin sensitivity. Results of in vitro chemotaxis studies in human monocytes suggested that the defect in chemotaxis observed ex vivo and in vivo in mice is also translatable to humans. Cumulatively, our data indicate that GPR21 has a critical function in coordinating macrophage proinflammatory activity in the context of obesity-induced insulin resistance. PMID:22653059

  8. Abdominal obesity is associated with stress urinary incontinence in Korean women.

    PubMed

    Han, Myung Ok; Lee, Nan Young; Park, Hye Soon

    2006-01-01

    This study investigated the relationship between abdominal obesity and stress urinary incontinence in Korean women. Women aged 30 and over, who visited the Department of Family Medicine of Asan Medical Center were recruited to participate in this study. Anthropometric measurements including body mass index (BMI) and waist circumference were taken, and associated factors of stress urinary incontinence was assessed by questionnaire. Stress urinary incontinence was significantly associated with physical work, vaginal delivery, and high waist circumference. In comparison with women in the lowest quartile of waist circumference, the odds ratios (OR) for stress urinary incontinence in women in the second, third, and fourth quartiles were increased significantly (1.79, 95% CI 1.07-2.98; 3.50, 95% CI 2.02-6.07; and 6.07, 95% CI 3.23-11.40, respectively). Our results indicate that high waist circumference may be a risk factor associated with stress urinary incontinence in women.

  9. Trehalose prevents adipocyte hypertrophy and mitigates insulin resistance in mice with established obesity.

    PubMed

    Arai, Chikako; Miyake, Masaki; Matsumoto, Yohsuke; Mizote, Akiko; Yoshizane, Chiyo; Hanaya, Yohko; Koide, Kazuhiro; Yamada, Mika; Hanaya, Toshiharu; Arai, Shigeyuki; Fukuda, Shigeharu

    2013-01-01

    Our group recently demonstrated that simultaneous administration of trehalose with a high-fat diet (HFD) suppresses adipocyte hypertrophy and mitigates insulin resistance in mice. For the present study, we hypothesized that similar effects of trehalose would be observed in mice with previously-established obesity. Obese mice were fed a HFD and drinking water containing 0.3 or 2.5% (weight/volume) trehalose or distilled water (DW) ad libitum for 8 wk. After 7 wk intake of a HFD and trehalose, fasting serum insulin levels and homeostasis model assessment-insulin resistance (HOMA-IR) in the 0.3% Tre/HFD group were significantly lower than those in the DW/HFD group (p<0.05). After 8 wk of treatment, mesenteric adipocytes in the 0.3% Tre/HFD group showed significantly less hypertrophy than those in the DW/HFD group. Mechanistic analysis indicated that levels of high molecular weight (HMW) adiponectin in the serum of the 0.3% Tre/HFD group were significantly higher than those in the DW/HFD group. The expression levels of insulin receptor substrate-1 (IRS-1) and insulin receptor substrate-2 (IRS-2) messenger RNA (mRNA) in muscle were also significantly increased by trehalose intake. Our data therefore suggest that administration of trehalose to obese mice mitigates insulin resistance by suppressing adipocyte hypertrophy and increasing serum HMW adiponectin, resulting in upregulation of IRS-1, and IRS-2 expression in muscle. These results further suggest that trehalose is a functional saccharide that may be used to prevent the progression of insulin resistance.

  10. Effects of dietary coconut oil on the biochemical and anthropometric profiles of women presenting abdominal obesity.

    PubMed

    Assunção, Monica L; Ferreira, Haroldo S; dos Santos, Aldenir F; Cabral, Cyro R; Florêncio, Telma M M T

    2009-07-01

    The effects of dietary supplementation with coconut oil on the biochemical and anthropometric profiles of women presenting waist circumferences (WC) >88 cm (abdominal obesity) were investigated. The randomised, double-blind, clinical trial involved 40 women aged 20-40 years. Groups received daily dietary supplements comprising 30 mL of either soy bean oil (group S; n = 20) or coconut oil (group C; n = 20) over a 12-week period, during which all subjects were instructed to follow a balanced hypocaloric diet and to walk for 50 min per day. Data were collected 1 week before (T1) and 1 week after (T2) dietary intervention. Energy intake and amount of carbohydrate ingested by both groups diminished over the trial, whereas the consumption of protein and fibre increased and lipid ingestion remained unchanged. At T1 there were no differences in biochemical or anthropometric characteristics between the groups, whereas at T2 group C presented a higher level of HDL (48.7 +/- 2.4 vs. 45.00 +/- 5.6; P = 0.01) and a lower LDL:HDL ratio (2.41 +/- 0.8 vs. 3.1 +/- 0.8; P = 0.04). Reductions in BMI were observed in both groups at T2 (P < 0.05), but only group C exhibited a reduction in WC (P = 0.005). Group S presented an increase (P < 0.05) in total cholesterol, LDL and LDL:HDL ratio, whilst HDL diminished (P = 0.03). Such alterations were not observed in group C. It appears that dietetic supplementation with coconut oil does not cause dyslipidemia and seems to promote a reduction in abdominal obesity.

  11. Dietary patterns of women are associated with incident abdominal obesity but not metabolic syndrome.

    PubMed

    Kimokoti, Ruth W; Gona, Philimon; Zhu, Lei; Newby, P K; Millen, Barbara E; Brown, Lisa S; D'Agostino, Ralph B; Fung, Teresa T

    2012-09-01

    Data on the relationship between empirical dietary patterns and metabolic syndrome (MetS) and its components in prospective study designs are limited. In addition, demographic and lifestyle determinants of MetS may modify the association between dietary patterns and the syndrome. We prospectively examined the relationship between empirically derived patterns and MetS and MetS components among 1146 women in the Framingham Offspring/Spouse cohort. They were aged 25-77 y with BMI ≥18.5 kg/m(2) and free of cardiovascular disease, diabetes, cancer, and MetS at baseline, and followed for a mean of 7 y. Five dietary patterns, Heart Healthier, Lighter Eating, Wine and Moderate Eating, Higher Fat, and Empty Calorie, were previously identified using cluster analysis from food intake collected using a FFQ. After adjusting for potential confounders, we observed lower odds for abdominal obesity for Higher Fat [OR = 0.48 (95% CI: 0.25, 0.91)] and Wine and Moderate Eating clusters [OR = 0.28 (95% CI: 0.11, 0.72)] compared with the Empty Calorie cluster. Additional adjustment for BMI somewhat attenuated these OR [Higher Fat OR = 0.52 (95% CI: 0.27, 1.00); Wine and Moderate Eating OR = 0.34 (95% CI: 0.13, 0.89)]. None of the clusters was associated with MetS or other MetS components. Baseline smoking status and age did not modify the relation between dietary patterns and MetS. The Higher Fat and Wine and Moderate Eating patterns showed an inverse association with abdominal obesity; certain foods might be targeted in these habitual patterns to achieve optimal dietary patterns for MetS prevention.

  12. Association of Circulating Irisin with Insulin Resistance and Oxidative Stress in Obese Women.

    PubMed

    Belviranli, M; Okudan, N; Çelik, F

    2016-09-01

    Irisin is a myokine/adipokine with potential role in obesity and diabetes. The purpose of the present study was to assess irisin levels and its association with insulin resistance and oxidative stress markers in premenopausal normal-weight and obese women. Ten obese (mean body mass index, 32.65±3.04 kg m(-2)) and 10 normal-weight (23.00±2.23 kg m(-2)) premenopausal women were involved in the present study. Anthropometric, and body composition parameters, blood chemistry, oxidative stress markers, and irisin concentrations of different groups were measured. Correlation analyses were performed between irisin and other measured parameters. Plasma irisin levels were lower in the obese group than the normal-weight group (p<0.05). Glucose, homeostasis model assessment index (HOMA-IR), and MDA levels in the obese group were higher than that in the normal-weight group (p<0.05). Plasma irisin was negatively correlated with insulin (r=-0.648, p<0.05), HOMA-IR (r=-0.664, p<0.05) and MDA (r=-0.690, p<0.05). These data suggest that irisin levels are decreased with obesity, and irisin may have an antidiabetic and antioxidant effects.

  13. Obesity and insulin resistance are associated with reduced activity in core memory regions of the brain.

    PubMed

    Cheke, Lucy G; Bonnici, Heidi M; Clayton, Nicola S; Simons, Jon S

    2017-02-01

    Increasing research in animals and humans suggests that obesity may be associated with learning and memory deficits, and in particular with reductions in episodic memory. Rodent models have implicated the hippocampus in obesity-related memory impairments, but the neural mechanisms underlying episodic memory deficits in obese humans remain undetermined. In the present study, lean and obese human participants were scanned using fMRI while completing a What-Where-When episodic memory test (the "Treasure-Hunt Task") that assessed the ability to remember integrated item, spatial, and temporal details of previously encoded complex events. In lean participants, the Treasure-Hunt task elicited significant activity in regions of the brain known to be important for recollecting episodic memories, such as the hippocampus, angular gyrus, and dorsolateral prefrontal cortex. Both obesity and insulin resistance were associated with significantly reduced functional activity throughout the core recollection network. These findings indicate that obesity is associated with reduced functional activity in core brain areas supporting episodic memory and that insulin resistance may be a key player in this association.

  14. Preventing High Fat Diet-induced Obesity and Improving Insulin Sensitivity through Neuregulin 4 Gene Transfer

    PubMed Central

    Ma, Yongjie; Gao, Mingming; Liu, Dexi

    2016-01-01

    Neuregulin 4 (NRG4), an epidermal growth factor-like signaling molecule, plays an important role in cell-to-cell communication during tissue development. Its function to regulate energy metabolism has recently been reported. This current study was designed to assess the preventive and therapeutic effects of NRG4 overexpression on high fat diet (HFD)-induced obesity. Using the hydrodynamic gene transfer method, we demonstrate that Nrg4 gene transfer in mice suppressed the development of diet-induced obesity, but did not affect pre-existing adiposity and body weight in obese mice. Nrg4 gene transfer curbed HFD-induced hepatic steatosis by inhibiting lipogenesis and PPARγ-mediated lipid storage. Concurrently, overexpression of NRG4 reduced chronic inflammation in both preventive and treatment studies, evidenced by lower mRNA levels of macrophage marker genes including F4/80, Cd68, Cd11b, Cd11c, and macrophage chemokine Mcp1, resulting in improved insulin sensitivity. Collectively, these results demonstrate that overexpression of the Nrg4 gene by hydrodynamic gene delivery prevents HFD-induced weight gain and fatty liver, alleviates obesity-induced chronic inflammation and insulin resistance, and supports the health benefits of NRG4 in managing obesity and obesity-associated metabolic disorders. PMID:27184920

  15. The Interactions of Obesity, Inflammation and Insulin Resistance in Breast Cancer

    PubMed Central

    Rose, David P.; Gracheck, Peter J.; Vona-Davis, Linda

    2015-01-01

    Obese postmenopausal women have an increased breast cancer risk, the principal mechanism for which is elevated estrogen production by adipose tissue; also, regardless of menstrual status and tumor estrogen dependence, obesity is associated with biologically aggressive breast cancers. Type 2 diabetes has a complex relationship with breast cancer risk and outcome; coexisting obesity may be a major factor, but insulin itself induces adipose aromatase activity and estrogen production and also directly stimulates breast cancer cell growth and invasion. Adipose tissue inflammation occurs frequently in obesity and type 2 diabetes, and proinflammatory cytokines and prostaglandin E2 produced by cyclooxygenase-2 in the associated infiltrating macrophages also induce elevated aromatase expression. In animal models, the same proinflammatory mediators, and the chemokine monocyte chemoattractant protein-1, also stimulate tumor cell proliferation and invasion directly and promote tumor-related angiogenesis. We postulate that chronic adipose tissue inflammation, rather than body mass index-defined obesity per se, is associated with an increased risk of type 2 diabetes and postmenopausal estrogen-dependent breast cancer. Also, notably before the menopause, obesity and type 2 diabetes, or perhaps the associated inflammation, promote estrogen-independent, notably triple-negative, breast cancer development, invasion and metastasis by mechanisms that may involve macrophage-secreted cytokines, adipokines and insulin. PMID:26516917

  16. The Effects of Combined Exercise on Health-Related Fitness, Endotoxin, and Immune Function of Postmenopausal Women with Abdominal Obesity.

    PubMed

    Park, Sung-Mo; Kwak, Yi-Sub; Ji, Jin-Goo

    2015-01-01

    This study was conducted to examine the effects of combined exercise on health-related fitness, endotoxin concentrations, and immune functions of postmenopausal women with abdominal obesity. 20 voluntary participants were recruited and they were randomly allocated to the combined exercise group (n = 10) or the control group (n = 10). Visceral obesity was defined as a visceral-to-subcutaneous fat ratio ≥ 0.4 based on computed tomography (CT) results. Body composition, exercise stress testing, fitness measurement, CT scan, and blood variables were analyzed to elucidate the effects of combined exercise. The SPSS Statistics 18.0 program was used to calculate means and standard deviations for all variables. Significant differences between the exercise group and control group were determined with 2-way ANOVA and paired t-tests. The exercise group's abdominal obesity was mitigated due to visceral fat reduction; grip strength, push-ups, and oxygen uptake per weight improved; and HDL-C and IgA level also increased, while TNF-α, CD14, and endotoxin levels decreased. Lowered TNF-α after exercise might have an important role in the obesity reduction. Therefore, we can conclude that combined exercise is effective in mitigating abdominal obesity, preventing metabolic diseases, and enhancing immune function.

  17. Chronic stress and comfort foods: self-medication and abdominal obesity.

    PubMed

    Dallman, Mary F; Pecoraro, Norman C; la Fleur, Susanne E

    2005-07-01

    Central corticotropin-releasing factor (CRF) networks are recruited by chronic stressors and elevated glucocorticoids (GCs) that initiate recruitment of central CRF activity in the amygdala. Increased central activity of the CRF network stimulates all monoaminergic cell groups, as well as premotor autonomic and other limbic structures resulting in the typical arousal, behavioral changes, autonomic, and neuroendocrine changes that accompany the chronic imposition of a stressor. By contrast, elevated GCs appear, through a variety of means to counteract the effects of central CRF, which they have initiated. Together with insulin, the GCs stimulate drive for and ingestion of "comfort foods" that may directly result in reduction of the negative effects of the chronic stressor in the nucleus Accumbens, through stimulation of the anterior, more pleasure-associated part of this cell group, thus reducing the weight of the stress-stimulated posterior, more defensive part. Furthermore, the shift in caloric intake from chow to preference for "comfort foods," together with elevated GCs and insulin, reorganize energy stores from a peripheral to a central distribution, primarily as abdominal fat. A signal associated with this fat depot appears, as with eating "comfort foods," to reduce the influence of the chronic stress network on behaviors, autonomic, and neuroendocrine outflow.

  18. Insulin Resistance, Dyslipidemia and Cardiovascular Changes in a Group of Obese Children

    PubMed Central

    Pires, António; Martins, Paula; Pereira, Ana Margarida; Silva, Patricia Vaz; Marinho, Joana; Marques, Margarida; Castela, Eduardo; Sena, Cristina; Seiça, Raquel

    2015-01-01

    Introduction Obesity-related comorbidities are present in young obese children, providing a platform for early adult cardiovascular disorders. Objectives To compare and correlate markers of adiposity to metabolic disturbances, vascular and cardiac morphology in a European pediatric obese cohort. Methods We carried out an observational and transversal analysis in a cohort consisting of 121 obese children of both sexes, between the ages of 6 and 17 years. The control group consisted of 40 children with normal body mass index within the same age range. Markers of adiposity, plasma lipids and lipoproteins, homeostasis model assessment-insulin resistance, common carotid artery intima-media thickness and left ventricular diameters were analyzed. Results There were statistically significant differences between the control and obese groups for the variables analyzed, all higher in the obese group, except for age, high-density lipoprotein cholesterol and adiponectin, higher in the control group. In the obese group, body mass index was directly correlated to left ventricular mass (r=0.542; p=0.001), the homeostasis model assessment-insulin resistance (r=0.378; p=<0.001) and mean common carotid artery intima-media thickness (r=0.378; p=<0.001). In that same group, insulin resistance was present in 38.1%, 12.5% had a combined dyslipidemic pattern, and eccentric hypertrophy was the most common left ventricular geometric pattern. Conclusions These results suggest that these markers may be used in clinical practice to stratify cardiovascular risk, as well as to assess the impact of weight control programs. PMID:25993589

  19. Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance.

    PubMed

    Holland, William L; Brozinick, Joseph T; Wang, Li-Ping; Hawkins, Eric D; Sargent, Katherine M; Liu, Yanqi; Narra, Krishna; Hoehn, Kyle L; Knotts, Trina A; Siesky, Angela; Nelson, Don H; Karathanasis, Sotirios K; Fontenot, Greg K; Birnbaum, Morris J; Summers, Scott A

    2007-03-01

    Insulin resistance occurs in 20%-25% of the human population, and the condition is a chief component of type 2 diabetes mellitus and a risk factor for cardiovascular disease and certain forms of cancer. Herein, we demonstrate that the sphingolipid ceramide is a common molecular intermediate linking several different pathological metabolic stresses (i.e., glucocorticoids and saturated fats, but not unsaturated fats) to the induction of insulin resistance. Moreover, inhibition of ceramide synthesis markedly improves glucose tolerance and prevents the onset of frank diabetes in obese rodents. Collectively, these data have two important implications. First, they indicate that different fatty acids induce insulin resistance by distinct mechanisms discerned by their reliance on sphingolipid synthesis. Second, they identify enzymes required for ceramide synthesis as therapeutic targets for combating insulin resistance caused by nutrient excess or glucocorticoid therapy.

  20. Dissociation of in vitro sensitivities of glucose transport and antilipolysis to insulin in NIDDM

    SciTech Connect

    Yki-Jaervinen, H.; Kubo, K.; Zawadzki, J.; Lillioja, S.; Young, A.; Abbott, W.; Foley, J.E.

    1987-09-01

    It is unclear from previous studies whether qualitative or only quantitative differences exist in insulin action in adipocytes obtained from obese subjects with non-insulin-dependent diabetes mellitus (NIDDM) when compared with equally obese nondiabetic subjects. In addition, the role of changes in insulin binding as a cause of insulin resistance in NIDDM is still controversial. The authors compared the sensitivities of (/sup 14/C)-glucose transport and antilipolysis to insulin and measured (/sup 125/I)-insulin binding in abdominal adipocytes obtained from 45 obese nondiabetic, obese diabetic, and 15 nonobese female southwestern American Indians. Compared with the nonobese group, the sensitivities of glucose transport antilipolysis were reduced in both the obese nondiabetic and obese diabetic groups. Compared with the obese nondiabetic subjects, the ED/sub 50/ for stimulation of glucose transport was higher in the obese patients with NIDDM. In contrast, the ED/sub 50/S for antilipolysis were similar in obese diabetic patients and obese nondiabetic subjects. No differences was found in insulin binding in patients with NIDDM when compared with the equally obese nondiabetic subjects. These data indicate 1) the mechanism of insulin resistance differs in NIDDM and obesity, and 2) the selective loss of insulin sensitivity in NIDDM precludes changes in insulin binding as a cause of insulin resistance in this disorder.

  1. Rosiglitazone improves insulin sensitivity and baroreflex gain in rats with diet-induced obesity.

    PubMed

    Zhao, Ding; McCully, Belinda H; Brooks, Virginia L

    2012-10-01

    Obesity decreases baroreflex gain (BRG); however, the mechanisms are unknown. We tested the hypothesis that impaired BRG is related to the concurrent insulin resistance, and, therefore, BRG would be improved after treatment with the insulin-sensitizing drug rosiglitazone. Male rats fed a high-fat diet diverged into obesity-prone (OP) and obesity-resistant (OR) groups after 2 weeks. Then, OP and OR rats, as well as control (CON) rats fed a standard diet, were treated daily for 2 to 3 weeks with rosiglitazone (3 or 6 mg/kg) or its vehicle by gavage. Compared with OR and CON rats, conscious OP rats exhibited reductions in BRG (OP, 2.9 ± 0.1 bpm/mm Hg; OR, 4.0 ± 0.2 bpm/mm Hg; CON, 3.9 ± 0.2 bpm/mm Hg; P < 0.05) and insulin sensitivity (hyperinsulinemic euglycemic clamp; OP, 6.8 ± 0.9 mg/kg · min; OR, 22.2 ± 1.2 mg/kg · min; CON, 17.7 ± 0.8 mg/kg · min; P < 0.05), which were well correlated (r(2) = 0.49; P < 0.01). In OP rats, rosiglitazone dose-dependently improved (P < 0.05) insulin sensitivity (12.8 ± 0.6 mg/kg · min at 3 mg/kg; 16.0 ± 1.5 mg/kg · min at 6 mg/kg) and BRG (3.8 ± 0.4 bpm/mm Hg at 3 mg/kg; 5.3 ± 0.7 bpm/mm Hg at 6 mg/kg). However, 6 mg/kg rosiglitazone also increased BRG in OR rats without increasing insulin sensitivity, disrupted the correlation between BRG and insulin sensitivity (r(2) = 0.08), and, in OP and OR rats, elevated BRG relative to insulin sensitivity (analysis of covariance; P < 0.05). Moreover, in OP rats, stimulation of the aortic depressor nerve, to activate central baroreflex pathways, elicited markedly reduced decreases in heart rate and arterial pressure, but these responses were not improved by rosiglitazone. In conclusion, diet-induced obesity impairs BRG via a central mechanism that is related to the concurrent insulin resistance. Rosiglitazone normalizes BRG, but not by improving brain baroreflex processing or insulin sensitivity.

  2. Emerging Perspectives on Essential Amino Acid Metabolism in Obesity and the Insulin-Resistant State12

    PubMed Central

    Adams, Sean H.

    2011-01-01

    Dysregulation of insulin action is most often considered in the context of impaired glucose homeostasis, with the defining feature of diabetes mellitus being elevated blood glucose concentration. Complications arising from the hyperglycemia accompanying frank diabetes are well known and epidemiological studies point to higher risk toward development of metabolic disease in persons with impaired glucose tolerance. Although the central role of proper blood sugar control in maintaining metabolic health is well established, recent developments have begun to shed light on associations between compromised insulin action [obesity, prediabetes, and type 2 diabetes mellitus (T2DM)] and altered intermediary metabolism of fats and amino acids. For amino acids, changes in blood concentrations of select essential amino acids and their derivatives, in particular BCAA, sulfur amino acids, tyrosine, and phenylalanine, are apparent with obesity and insulin resistance, often before the onset of clinically diagnosed T2DM. This review provides an overview of these changes and places recent observations from metabolomics research into the context of historical reports in the areas of biochemistry and nutritional biology. Based on this synthesis, a model is proposed that links the FFA-rich environment of obesity/insulin resistance and T2DM with diminution of BCAA catabolic enzyme activity, changes in methionine oxidation and cysteine/cystine generation, and tissue redox balance (NADH/NAD+). PMID:22332087

  3. IMPLICATIONS OF CROSSTALK BETWEEN LEPTIN AND INSULIN SIGNALING DURING THE DEVELOPMENT OF DIET INDUCED OBESITY

    PubMed Central

    Morrison, Christopher D; Huypens, Peter; Stewart, Laura K; Gettys, Thomas W

    2009-01-01

    SUMMARY Insulin and leptin play complementary roles in regulating the consumption, uptake, oxidation and storage of nutrients. Chronic consumption of diets that contain a high proportion of calories from saturated fat induces a progressive deterioration in function of both hormones. Certain rat lines and strains of mice are particularly sensitive to the obesogenic and diabetogenic effects of high fat diets, and have been used extensively to study the developmental progression of insulin and leptin resistance in relation to the increasing adiposity that is characteristic of their response to these diets. Some aspects of the diminished efficacy of each hormone are secondary to increased adiposity but a consensus is emerging to support the view that direct effects of dietary components or their metabolites, independent of the resulting obesity, play important roles in development of insulin and leptin resistance. In this minireview, we will examine the implications of crosstalk between leptin and insulin signaling during the development of diet-induced obesity, emphasizing potential interactions between pathways that occur among target sites, and exploring how these interactions may influence the progression of obesity and diabetes. PMID:18852044

  4. 4-Hydroxyisoleucine from Fenugreek (Trigonella foenum-graecum): Effects on Insulin Resistance Associated with Obesity.

    PubMed

    Avalos-Soriano, Anaguiven; De la Cruz-Cordero, Ricardo; Rosado, Jorge L; Garcia-Gasca, Teresa

    2016-11-22

    Obesity and insulin resistance (IR) are interdependent multifactorial processes that cannot be understood separately. Obesity leads to systemic inflammation and increased levels of free fatty acids that provoke IR and lipotoxicity. At the same time, IR exacerbates adipose cell dysfunction, resulting in chronic inflammation and major lipotoxic effects on nonadipose tissues. 4-Hydroxyisoleucine (4-OHIle), a peculiar nonprotein amino acid isolated from fenugreek (Trigonella foenum-graecum) seeds, exhibits interesting effects on IR related to obesity. 4-OHIle increases glucose-induced insulin release, and the insulin response mediated by 4-OHIle depends on glucose concentration. The beneficial effects observed are related to the regulation of blood glucose, plasma triglycerides, total cholesterol, free fatty acid levels, and the improvement of liver function. The mechanism of action is related to increased Akt phosphorylation and reduced activation of Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB. Here, we present a review of the research regarding the insulinotropic and insulin-sensitising activity of 4-OHIle in in vitro and in vivo models.

  5. Fibroblast growth factor-21 restores insulin sensitivity but induces aberrant bone microstructure in obese insulin-resistant rats.

    PubMed

    Charoenphandhu, Narattaphol; Suntornsaratoon, Panan; Krishnamra, Nateetip; Sa-Nguanmoo, Piangkwan; Tanajak, Pongpun; Wang, Xiaojie; Liang, Guang; Li, Xiaokun; Jiang, Chao; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2017-03-01

    Fibroblast growth factor (FGF)-21 is a potent endocrine factor that improves insulin resistance and obesity-associated metabolic disorders. However, concomitant activation of peroxisome proliferator-activated receptor-γ by FGF-21 makes bone susceptible to osteopenia and fragility fracture. Since an increase in body weight often induced adaptive change in bone by making it resistant to fracture, it was unclear whether FGF-21 would still induce bone defects in overweight rats. Therefore, the present study aimed to investigate bone microstructure and its mechanical properties in high fat diet (HF)-fed rats treated with 0.1 mg/kg/day FGF-21. Eighteen male rats were divided into two groups to receive either a normal diet or HF for 12 weeks. HF rats were then divided into two subgroups to receive either vehicle or FGF-21 for 4 weeks. The results showed that HF led to obesity, dyslipidemia and insulin resistance, as indicated by hyperinsulinemia with euglycemia. In HF rats, there was an increase in tibial yield displacement (an indicator of ability to be deformed without losing toughness, as determined by 3-point bending) without changes in tibial trabecular volumetric bone mineral density (vBMD) or cortical bone parameters, e.g., cortical thickness and bone area. FGF-21 treatment strongly improved the metabolic parameters and increased insulin sensitivity in HF rats. However, FGF-21-treated HF rats showed lower yield displacement, trabecular vBMD, trabecular bone volume, trabecular thickness, and osteoblast surface compared with vehicle-treated HF rats. These findings suggest that, despite being a potent antagonist of insulin resistance and visceral fat accumulation, FGF-21 is associated with bone defects in HF rats.

  6. Histological and biochemical study of the superficial abdominal fascia and its implication in obesity

    PubMed Central

    Kumar, Pramod; Aithal, Srinivas Kodavoor; Kotian, Sushma R.; Thittamaranahalli, Honnegowda; Bangera, Hemalatha; Prasad, Keerthana; Souza, Anne D.

    2016-01-01

    The advancement of liposculpturing and fascial flaps in reconstructive surgery has renewed interest in the superficial fascia of abdomen. Its histological and biochemical composition may play a vital role in maintaining strength and elasticity of the fascia. Hence, study of abdominal fascia for the elastic, collagen, and hydroxyproline contents is desirable to understand asymmetrical bulges and skin folds and in improving surgical treatment of obesity. Samples of superficial fascia were collected from of upper and lower abdomen from 21 fresh cadavers (15 males and 6 females). Samples were stained using Verhoeff–Van Gieson stain. Digital images of superficial fascia were analyzed using TissueQuant software. The samples were also subjected to hydroxyproline estimation. The superficial fascia was formed by loosely packed collagen fibers mixed with abundant elastic fibers and adipose tissue. Elastic contents and collagen contents of superficial fascia were significantly more in the upper abdomen than that in the lower abdomen in males. Hydroxyproline content of superficial fascia of upper abdomen was significantly more than that of lower abdomen in both males and females. The elastic, collagen and hydroxyproline contents of superficial fascia of upper abdomen were higher compared to the lower abdomen. This may be a reason for asymmetric bulging over abdomen and more sagging fold of skin in the lower abdomen than in the upper abdomen. This study may therefore be helpful in finding new ways to manage obesity and other body contour deformities. PMID:27722011

  7. Obesity and insulin resistance in resistant hypertension: implications for the kidney.

    PubMed

    Rao, Akhilesh; Pandya, Vishwam; Whaley-Connell, Adam

    2015-05-01

    There is recognition that the obesity epidemic contributes substantially to the increasing incidence of CKD and resistant hypertension (HTN). The mechanisms by which obesity promotes resistance are an area of active interest and intense investigation. It is thought that increases in visceral adiposity lead to a proinflammatory, pro-oxidative milieu that promote resistance to the metabolic actions of insulin. This resistance to insulin at the level of skeletal muscle tissue impairs glucose disposal/utilization through actions on the endothelium that include vascular rarefaction, reductions in vascular relaxation, and vascular remodeling. Insulin resistance derived from increased adipose tissue and obesity has system-wide implications for other tissue beds such as the kidney that affects blood pressure regulation. The additional autocrine and paracrine activities of adipose tissue contribute to inappropriate activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system that promote kidney microvascular remodeling, stiffness, and sodium (Na(+)) retention that in turn promote HTN and in the CKD patient, resistance. In this review, we will summarize the important mechanisms that link obesity to CKD as they relate to resistant HTN.

  8. Inflammasome is a central player in the induction of obesity and insulin resistance.

    PubMed

    Stienstra, Rinke; van Diepen, Janna A; Tack, Cees J; Zaki, Md Hasan; van de Veerdonk, Frank L; Perera, Deshani; Neale, Geoffrey A; Hooiveld, Guido J; Hijmans, Anneke; Vroegrijk, Irene; van den Berg, Sjoerd; Romijn, Johannes; Rensen, Patrick C N; Joosten, Leo A B; Netea, Mihai G; Kanneganti, Thirumala-Devi

    2011-09-13

    Inflammation plays a key role in the pathogenesis of obesity. Chronic overfeeding leads to macrophage infiltration in the adipose tissue, resulting in proinflammatory cytokine production. Both microbial and endogenous danger signals trigger assembly of the intracellular innate immune sensor Nlrp3, resulting in caspase-1 activation and production of proinflammatory cytokines IL-1β and IL-18. Here, we showed that mice deficient in Nlrp3, apoptosis-associated speck-like protein, and caspase-1 were resistant to the development of high-fat diet-induced obesity, which correlated with protection from obesity-induced insulin resistance. Furthermore, hepatic triglyceride content, adipocyte size, and macrophage infiltration in adipose tissue were all reduced in mice deficient in inflammasome components. Monocyte chemoattractant protein (MCP)-1 is a key molecule that mediates macrophage infiltration. Indeed, defective inflammasome activation was associated with reduced MCP-1 production in adipose tissue. Furthermore, plasma leptin and resistin that affect energy use and insulin sensitivity were also changed by inflammasome-deficiency. Detailed metabolic and molecular phenotyping demonstrated that the inflammasome controls energy expenditure and adipogenic gene expression during chronic overfeeding. These findings reveal a critical function of the inflammasome in obesity and insulin resistance, and suggest inhibition of the inflammasome as a potential therapeutic strategy.

  9. Tyrosine Is Associated with Insulin Resistance in Longitudinal Metabolomic Profiling of Obese Children

    PubMed Central

    Hellmuth, Christian; Kirchberg, Franca Fabiana; Lass, Nina; Harder, Ulrike; Peissner, Wolfgang; Koletzko, Berthold; Reinehr, Thomas

    2016-01-01

    In obese children, hyperinsulinaemia induces adverse metabolic consequences related to the risk of cardiovascular and other disorders. Branched-chain amino acids (BCAA) and acylcarnitines (Carn), involved in amino acid (AA) degradation, were linked to obesity-associated insulin resistance, but these associations yet have not been studied longitudinally in obese children. We studied 80 obese children before and after a one-year lifestyle intervention programme inducing substantial weight loss >0.5 BMI standard deviation scores in 40 children and no weight loss in another 40 children. At baseline and after the 1-year intervention, we assessed insulin resistance (HOMA index), fasting glucose, HbA1c, 2 h glucose in an oral glucose tolerance test, AA, and Carn. BMI adjusted metabolite levels were associated with clinical markers at baseline and after intervention, and changes with the intervention period were evaluated. Only tyrosine was significantly associated with HOMA (p < 0.05) at baseline and end and with change during the intervention (p < 0.05). In contrast, ratios depicting BCAA metabolism were negatively associated with HOMA at baseline (p < 0.05), but not in the longitudinal profiling. Stratified analysis revealed that the children with substantial weight loss drove this association. We conclude that tyrosine alterations in association with insulin resistance precede alteration in BCAA metabolism. This trial is registered with ClinicalTrials.gov Identifier NCT00435734. PMID:26881241

  10. Association of Osteoprotegerin with Obesity, Insulin Resistance and Non-Alcoholic Fatty Liver Disease in Children

    PubMed Central

    Erol, Meltem; Bostan Gayret, Ozlem; Tekin Nacaroglu, Hikmet; Yigit, Ozgul; Zengi, Oguzhan; Salih Akkurt, Mehmet; Tasdemir, Mehmet

    2016-01-01

    Background Osteoprotegerin (OPG) is a member of the tumor necrosis factor superfamily. Reduced OPG levels are related to obesity, insulin resistance, and non-alcoholic fatty liver disease (NAFLD). Objectives The aim of this study was to evaluate the relationship between OPG levels, obesity, insulin resistance, and NAFLD in pediatric patients. Methods This was a prospective, cross-sectional, controlled study that was conducted in the department of pediatrics at Bagcilar training and research hospital in Istanbul, Turkey, between April and August 2015. The study was performed on 107 children with obesity and 37 controls aged 5 - 17 years. In the obese subset, 62 patients had NAFLD. Homeostatic model assessment-insulin resistance (HOMA-IR) was used to calculate insulin resistance. Insulin resistance was defined as a HOMA-IR value greater than 2.5. Plasma OPG levels were measured using enzyme-linked immunosorbent assays. NAFLD was diagnosed by hepatic ultrasound. Results The mean age was 11.25 ± 3.38 years in the patient group and 10.41 ± 3.15 years in the control group. The OPG level in the obese group with the mean of 55.20 ± 24.55 pg/mL (median = 48.81 pg/mL) was significantly lower than that in the control group with the mean of 70.78 ± 33.41 pg/mL (median = 64.57 pg/mL) (P = 0.0001). The optimal cut-off point (sensitivity, specificity) of the OPG level for the diagnosis of obesity was ≤ 46, 19 pg/mL. According to logistic regression analysis, fasting insulin (P = 0.036) and OPG (P = 0.01) levels were most affected by obesity. In the obese patients, who had HOMA-IR < 2.5, the mean level of OPG was 58.91 ± 6.88729 pg/mL (median = 49.55). In the obese patients, who had HOMA-IR ≥ 2.5, the mean level of OPG was 54.19 ± 22.21 pg/mL (median = 48.47). No significant correlations were found between OPG and HOMA-IR (P = 0.791). No statistically significant difference was observed in the mean OPG between patients with hepatosteatosis (mean = 54.55 ± 25.01 pg

  11. Early diet, insulin-like growth factor-1, growth and later obesity.

    PubMed

    Michaelsen, Kim F; Larnkjaer, Anni; Molgaard, Christian

    2013-01-01

    There is increasing evidence that factors in early life are important for the risk of developing overweight and obesity later in childhood. Among the postnatal factors, breastfeeding and complementary feeding are especially interesting because the pattern of these two factors can be changed. Breastfeeding has been shown to reduce the risk of later obesity, although the effect is not substantial. Complementary feeding also seems to play a role. There is some evidence that a high protein intake is associated with a higher risk of obesity later in childhood, whereas a high fat intake during the complementary feeding period does not seem to be a risk factor for later obesity. Thus, the dietary pattern during this period is different from the pattern seen in older children and adults where a high fat intake is associated with a higher risk of obesity and a high protein intake in some studies seems to protect against obesity. A few studies have also suggested that early introduction of complementary foods (before age 4 months) is associated with an increased risk of later obesity. A high weight gain during early life, especially the first 6 months, is associated with a higher risk of developing obesity. However, some studies suggest that weight gain during the 6- to 12-month age period, when complementary feeding is introduced, is not associated with later obesity. Insulin-like growth factor-1 (IGF-1) values and body composition both play a role in the complex pattern between early diet and later obesity, but our present knowledge about how these factors are influenced by diet during infancy is limited. Future studies should include longitudinal data on IGF-1 and body composition during infancy to improve our understanding of how diet in early life can play a role in prevention of later obesity.

  12. Metabolic Syndrome, Insulin Resistance and Fatty Liver in Obese Iranian Children

    PubMed Central

    Saki, Forough; Karamizadeh, Zohreh

    2014-01-01

    Background: Obesity is a global epidemic and its morbidities such as metabolic syndrome, insulin resistance, and fatty liver leads to a spectrum of psycho-social and medical consequences. Objectives: The objective of this study was to investigate the prevalence of fatty liver in obese Iranian children and its' association with metabolic syndrome and insulin resistance. Patients and Methods: 102 obese Iranian children, referred to pediatric clinics from March 2011 to March 2012, were enrolled in this cross-sectional study. All the patients were visited by a pediatric endocrinologist, a pediatric gastroenterologist and an expert radiologist in the evaluation of fatty liver grading. Results: The grade of fatty liver was higher in older children (P = 0.001). It was also more in taller and heavier children (P = 0.000). The more the BMI was, the more the fatty liver grade was (P = 0.002). Severity of fatty liver according to liver sonography in patient had a positive relationship with waist circumference, hip circumference, serum TG, serum FBS, serum fasting insulin, serum ALT, systolic blood pressure and HOMA index and had a negative correlation with the level of alkaline phosphatase. Severity of fatty liver also had a close relationship with the presence of acanthosis nigricans and HOMA index. Conclusions: Prevalence of fatty liver is high in our obese children. It was associated with criteria of metabolic syndrome and insulin resistance, so visceral fat may participate in the pathogenesis of the metabolic syndrome or merely serve as a marker of increased risk for the metabolic complications of obesity. PMID:25031864

  13. Chronic kidney disease and obesity bias surrogate estimates of insulin sensitivity compared with the hyperinsulinemic euglycemic clamp.

    PubMed

    Ahmad, Iram; Zelnick, Leila R; Robinson, Nicole R; Hung, Adriana M; Kestenbaum, Bryan; Utzschneider, Kristina M; Kahn, Steven E; de Boer, Ian H

    2017-03-01

    Insulin sensitivity can be measured by procedures such as the hyperinsulinemic euglycemic clamp or by using surrogate indices. Chronic kidney disease (CKD) and obesity may differentially affect these measurements because of changes in insulin kinetics and organ-specific effects on insulin sensitivity. In a cross-sectional study of 59 subjects with nondiabetic CKD [estimated glomerular filtration rate: (GFR) <60 ml·min(-1)·1.73 m(2)] and 39 matched healthy controls, we quantified insulin sensitivity by clamp (SIclamp), oral glucose tolerance test, and fasting glucose and insulin. We compared surrogate insulin sensitivity indices to SIclamp using descriptive statistics, graphical analyses, correlation coefficients, and linear regression. Mean age was 62.6 yr; 48% of the participants were female, and 77% were Caucasian. Insulin sensitivity indices were 8-38% lower in participants with vs. without CKD and 13-59% lower in obese compared with nonobese participants. Correlations of surrogate indices with SIclamp did not differ significantly by CKD or obesity status. Adjusting for SIclamp in addition to demographic factors, Matsuda index was 15% lower in participants with vs. without CKD (P = 0.09) and 36% lower in participants with vs. without obesity (P = 0.0001), whereas 1/HOMA-IR was 23% lower in participants with vs. without CKD (P = 0.02) and 46% lower in participants with vs. without obesity (P < 0.0001). We conclude that CKD and obesity do not significantly alter correlations of surrogate insulin sensitivity indices with SIclamp, but they do bias surrogate measurements of insulin sensitivity toward lower values. This bias may be due to differences in insulin kinetics or organ-specific responses to insulin.

  14. Pregnancy restores insulin secretion from pancreatic islets in cafeteria diet-induced obese rats.

    PubMed

    Vanzela, E C; Ribeiro, R A; de Oliveira, C A Machado; Rodrigues, F B; Bonfleur, M L; Carneiro, E M; Souza, K L A; Boschero, A C

    2010-02-01

    Insulin resistance during pregnancy is counteracted by enhanced insulin secretion. This condition is aggravated by obesity, which increases the risk of gestational diabetes. Therefore, pancreatic islet functionality was investigated in control nonpregnant (C) and pregnant (CP), and cafeteria diet-fed nonpregnant (Caf), and pregnant (CafP) obese rats. Isolated islets were used for measurements of insulin secretion (RIA), NAD(P)H production (MTS), glucose oxidation ((14)CO(2) production), intracellular Ca(2+) levels (fura-2 AM), and gene expression (real-time PCR). Impaired glucose tolerance was clearly established in Caf and CafP rats at the 14th wk on a diet. Insulin secretion induced by direct depolarizing agents such as KCl and tolbutamide and increasing concentrations of glucose was significantly reduced in Caf, compared with C islets. This reduction was not observed in islets from CP and CafP rats. Accordingly, the glucose oxidation and production of reduced equivalents were increased in CafP islets. The glucose-induced Ca(2+) increase was significantly lower in Caf and higher in CafP, compared with all other groups. CP and CafP islets demonstrated an increased Ca(2+) oscillation frequency, compared with both C and Caf islets, and the amplitude of oscillations was augmented in CafP, compared with Caf islets. In addition, Ca(v)alpha1.2 and SERCA2a mRNA levels were reduced in Caf islets. Ca(v)alpha1.2, but not SERCA2a, mRNA was normalized in CafP islets. In conclusion, cafeteria diet-induced obesity impairs insulin secretion. This alteration is related to the impairment of Ca(2+) handling in pancreatic islets, in especial Ca(2+) influx, a defect that is reversed during pregnancy allowing normalization of insulin secretion.

  15. GADD34-deficient mice develop obesity, nonalcoholic fatty liver disease, hepatic carcinoma and insulin resistance

    PubMed Central

    Nishio, Naomi; Isobe, Ken-ichi

    2015-01-01

    The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing in parallel with the prevalence of obesity. DNA damage-inducible protein 34 (GADD34/Ppp1r15a), originally isolated from UV-inducible transcripts in Chinese hamster ovary (CHO) cells, dephosphorylates several kinases that function in important signaling cascades, including dephosphorylation of eIF2α. We examined the effects of GADD34 on natural life span by using GADD34-deficient mice. Here we observed for the first time that with age GADD34-deficient mice become obese, developing fatty liver followed by liver cirrhosis, hepatocellular carcinoma, and insulin resistance. We found that myofibroblasts and immune cells infiltrated the portal veins of aged GADD34-deficient mouse livers. A high-fat diet (HFD) induced a higher level of steatosis in young GADD34-deficient mice compared with WT mice. Differentiation into fat is dependent on insulin signaling. Insulin signaling in young GADD34-deficient mice was higher than that in WT mice, which explained the higher fat differentiation of mouse embryonic fibroblasts (MEFs) observed in GADD34-deficient mice. Through aging or a HFD, insulin signaling in GADD34-deficient liver converted to be down regulated compared with WT mice. We found that a HFD or palmitate treatment converted insulin signaling by up-regulating TNF-α and JNK. PMID:26316333

  16. Serum Fatty Acids, Desaturase Activities and Abdominal Obesity – A Population-Based Study of 60-Year Old Men and Women

    PubMed Central

    Alsharari, Zayed D.; Risérus, Ulf; Leander, Karin; Sjögren, Per; Carlsson, Axel C.; Vikström, Max; Laguzzi, Federica; Gigante, Bruna; Cederholm, Tommy; De Faire, Ulf; Hellénius, Mai-Lis

    2017-01-01

    Abdominal obesity is a key contributor of metabolic disease. Recent trials suggest that dietary fat quality affects abdominal fat content, where palmitic acid and linoleic acid influence abdominal obesity differently, while effects of n-3 polyunsaturated fatty acids are less studied. Also, fatty acid desaturation may be altered in abdominal obesity. We aimed to investigate cross-sectional associations of serum fatty acids and desaturases with abdominal obesity prevalence in a population-based cohort study. Serum cholesteryl ester fatty acids composition was measured by gas chromatography in 60-year old men (n = 1883) and women (n = 2015). Cross-sectional associations of fatty acids with abdominal obesity prevalence and anthropometric measures (e.g., sagittal abdominal diameter) were evaluated in multivariable-adjusted logistic and linear regression models, respectively. Similar models were employed to investigate relations between desaturase activities (estimated by fatty acid ratios) and abdominal obesity. In logistic regression analyses, palmitic acid, stearoyl-CoA-desaturase and Δ6-desaturase indices were associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals) for highest versus lowest quartiles were 1.45 (1.19–1.76), 4.06 (3.27–5.05), and 3.07 (2.51–3.75), respectively. Linoleic acid, α-linolenic acid, docohexaenoic acid, and Δ5-desaturase were inversely associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals): 0.39 (0.32–0.48), 0.74 (0.61–0.89), 0.76 (0.62–0.93), and 0.40 (0.33–0.49), respectively. Eicosapentaenoic acid was not associated with abdominal obesity. Similar results were obtained from linear regression models evaluating associations with different anthropometric measures. Sex-specific and linear associations were mainly observed for n3-polyunsaturated fatty acids, while associations of the other exposures were generally non-linear and similar across

  17. Excessive Refined Carbohydrates and Scarce Micronutrients Intakes Increase Inflammatory Mediators and Insulin Resistance in Prepubertal and Pubertal Obese Children Independently of Obesity

    PubMed Central

    López-Alarcón, Mardia; Perichart-Perera, Otilia; Rodríguez-Cruz, Maricela; Armenta-Álvarez, Andrea; Bram-Falcón, María Teresa; Mayorga-Ochoa, Marielle

    2014-01-01

    Background. Low-grade inflammation is the link between obesity and insulin resistance. Because physiologic insulin resistance occurs at puberty, obese pubertal children are at higher risk for insulin resistance. Excessive diets in refined carbohydrates and saturated fats are risk factors for insulin resistance, but calcium, magnesium, vitamin-D, and the omega-3 fatty acids likely protect against inflammation and insulin resistance. Objective. To analyze interactions among dietary saturated fat, refined carbohydrates, calcium, magnesium, vitamin D, and omega-3 fatty acids on the risk of inflammation and insulin resistance in a sample of prepubertal and pubertal children. Methods. A sample of 229 children from Mexico City was analyzed in a cross-sectional design. Anthropometric measurements, 24 h recall questionnaires, and blood samples were obtained. Serum insulin, glucose, calcium, magnesium, 25-OHD3, C-reactive protein, leptin, adiponectin, and erythrocytes fatty acids were measured. Parametric and nonparametric statistics were used for analysis. Results. While mean macronutrients intake was excessive, micronutrients intake was deficient (P < 0.01). Inflammation determinants were central obesity and magnesium-deficient diets. Determinants of insulin resistance were carbohydrates intake and circulating magnesium and adiponectin. Conclusions. Magnesium-deficient diets are determinants of inflammation, while high intake of refined carbohydrates is a risk factor for insulin resistance, independently of central adiposity. PMID:25477716

  18. Alteration of local adipose tissue trace element homeostasis as a possible mechanism of obesity-related insulin resistance.

    PubMed

    Tinkov, Alexey A; Sinitskii, Anton I; Popova, Elizaveta V; Nemereshina, Olga N; Gatiatulina, Evgenia R; Skalnaya, Margarita G; Skalny, Anatoly V; Nikonorov, Alexandr A

    2015-09-01

    The mechanisms of association between obesity and the related metabolic disturbances in general and insulin resistance in particular are extensively studied. Taking into account a key role of adipose tissue insulin resistance in the development of systemic obesity-related insulin resistance, the estimation of mechanisms linking increased adiposity and impaired insulin signaling in adipocytes will allow to develop novel prophylactic and therapeutic approaches to treatment of these states. A number of trace elements like chromium, zinc, and vanadium have been shown to take part in insulin signaling via various mechanisms. Taking into account a key role of adipocyte in systemic carbohydrate homeostasis it can be asked if trace element homeostasis in adipose tissue may influence regulatory mechanisms of glucose metabolism. We hypothesize that caloric excess through currently unknown mechanisms results in decreased chromium, vanadium, and zinc content in adipocytes. Decreased content of trace elements in the adipose tissue causes impairment of intra-adipocyte insulin signaling subsequently leading to adipose tissue insulin resistance. The latter significantly contributes to systemic insulin resistance and further metabolic disruption in obesity. It is also possible that decreased adipose tissue trace element content is associated with dysregulation of insulin-sensitizing and proinflammatory adipokines also leading to insulin resistance. We hypothesize that insulin resistance and adipokine dysbalance increase the severity of obesity subsequently aggravating alteration of adipose tissue trace element balance. Single indications of high relative adipose tissue trace element content, decreased Cr, V, and Zn content in obese adipose tissue, and tight association between fat tissue chromium, vanadium, and zinc levels and metabolic parameters in obesity may be useful for hypothesis validation. If our hypothesis will be confirmed by later studies, adipose tissue chromium

  19. Melatonin improves insulin sensitivity independently of weight loss in old obese rats.

    PubMed

    Zanuto, Ricardo; Siqueira-Filho, Mário A; Caperuto, Luciana C; Bacurau, Reury F P; Hirata, Emiko; Peliciari-Garcia, Rodrigo A; do Amaral, Fernanda Gaspar; Marçal, Anderson C; Ribeiro, Luciene M; Camporez, João P G; Carpinelli, Angelo Rafael; Bordin, Silvana; Cipolla-Neto, José; Carvalho, Carla R O

    2013-09-01

    In aged rats, insulin signaling pathway (ISP) is impaired in tissues that play a pivotal role in glucose homeostasis, such as liver, skeletal muscle, and adipose tissue. Moreover, the aging process is also associated with obesity and reduction in melatonin synthesis from the pineal gland and other organs. The aim of the present work was to evaluate, in male old obese Wistar rats, the effect of melatonin supplementation in the ISP, analyzing the total protein amount and the phosphorylated status (immunoprecipitation and immunoblotting) of the insulin cascade components in the rat hypothalamus, liver, skeletal muscle, and periepididymal adipose tissue. Melatonin was administered in the drinking water for 8- and 12 wk during the night period. Food and water intake and fasting blood glucose remained unchanged. The insulin sensitivity presented a 2.1-fold increase both after 8- and 12 wk of melatonin supplementation. Animals supplemented with melatonin for 12 wk also presented a reduction in body mass. The acute insulin-induced phosphorylation of the analyzed ISP proteins increased 1.3- and 2.3-fold after 8- and 12 wk of melatonin supplementation. The total protein content of the insulin receptor (IR) and the IR substrates (IRS-1, 2) remained unchanged in all investigated tissues, except for the 2-fold increase in the total amount of IRS-1 in the periepididymal adipose tissue. Therefore, the known age-related melatonin synthesis reduction may also be involved in the development of insulin resistance and the adequate supplementation could be an important alternative for the prevention of insulin signaling impairment in aged organisms.

  20. Microarray profiling of isolated abdominal subcutaneous adipocytes from obese vs non-obese Pima Indians: increased expression of inflammation-related genes

    PubMed Central

    Lee, Y. H.; Nair, S.; Rousseau, E.; Tataranni, P. A.; Bogardus, C.; Allison, D. B.; Page, G. P.

    2006-01-01

    Aims/hypothesis: Obesity increases the risk of developing major diseases such as diabetes and cardiovascular disease. Adipose tissue, particularly adipocytes, may play a major role in the development of obesity and its comorbidities. The aim of this study was to characterise, in adipocytes from obese people, the most differentially expressed genes that might be relevant to the development of obesity. Methods: We carried out microarray gene profiling of isolated abdominal subcutaneous adipocytes from 20 non-obese (BMI 25±3 kg/m2) and 19 obese (BMI 55± 8 kg/m2) non-diabetic Pima Indians using Affymetrix HG-U95 GeneChip arrays. After data analyses, we measured the transcript levels of selected genes based on their biological functions and chromosomal positions using quantitative real-time PCR. Results: The most differentially expressed genes in adipocytes of obese individuals consisted of 433 upregulated and 244 downregulated genes. Of these, 410 genes could be classified into 20 functional Gene Ontology categories. The analyses indicated that the inflammation/immune response category was over-represented, and that most inflammation-related genes were upregulated in adipocytes of obese subjects. Quantitative real-time PCR confirmed the transcriptional upregulation of representative inflammation-related genes (CCL2 and CCL3) encoding the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein 1α. The differential expression levels of eight positional candidate genes, including inflammation-related THY1 and C1QTNF5, were also confirmed. These genes are located on chromosome 11q22-q24, a region with linkage to obesity in the Pima Indians. Conclusions/interpretation: This study provides evidence supporting the active role of mature adipocytes in obesity-related inflammation. It also provides potential candidate genes for susceptibility to obesity. PMID:16059715

  1. Prevalence of general and abdominal obesity in the adult population of Spain, 2008-2010: the ENRICA study.

    PubMed

    Gutiérrez-Fisac, J L; Guallar-Castillón, P; León-Muñoz, L M; Graciani, A; Banegas, J R; Rodríguez-Artalejo, F

    2012-04-01

    This is the first study to report the prevalence of general obesity and abdominal obesity (AO) in the adult population of Spain based on measurements of weight, height and waist circumference. The data are taken from the ENRICA study, a cross-sectional study carried out between June 2008 and October 2010 in 12,883 individuals representative of the non-institutionalized population on Spain aged 18 years and older. Anthropometry was performed under standardized conditions in the households by trained interviewers. Overweight was considered as body mass index (BMI) 25-29.9 kg m(-2) , and obesity as BMI ≥ 30 kg m(-2) . AO was defined as waist circumference >102 cm in men and >88 cm in women. The prevalence of obesity was 22.9% (24.4% in men and 21.4% in women). About 36% of adults had AO (32% of men and 39% of women). The frequency of obesity and of AO increased with age and affected, respectively, 35 and 62% of persons aged 65 and over. The frequency of obesity and AO decreased with increasing educational level. For example, 29% of women with primary education or less had obesity vs. only 11% of those with university studies. The prevalence of obesity was very high in the Canary Islands and in the south of Spain.

  2. Exenatide improves liver mitochondrial dysfunction and insulin resistance by reducing oxidative stress in high fat diet-induced obese mice.

    PubMed

    Wang, Zixuan; Hou, Lin; Huang, Lanhui; Guo, Jun; Zhou, Xinli

    2017-04-22

    Oxidative stress is associated with obesity and may be accompanied by liver insulin resistance and mitochondrial dysfunction. Decreased mitochondrial respiratory chain enzymatic activities and decreased insulin metabolic signaling may promote these maladaptive changes. In this context, exenatide has been reported to reduce hepatic lipid deposition, improve insulin sensitivity and improve mitochondrial dysfunction. We hypothesized that exenatide would attenuate mitochondrial dysfunction by reducing hepatic lipid deposition, blunting oxidant stress and promoting insulin metabolic signaling in a high fat diet-induced model of obesity and insulin resistance. Sixteen-week-old male C57BL/6 diet-induced obese (DIO) mices and age-matched standard diet (STD) mices were treated with exenatide (10 μg/kg twice a day) for 28 days. Compared with untreated STD mice, untreated DIO mice exhibited deposited excessive lipid in liver and produced the oxidative stress in conjunction with insulin resistance, abnormal hepatic cells and mitochondrial histoarchitecture, mitochondrial dysfunction and reduced organism metabolism. Exenatide reduced hepatic steatosis, decreased oxidative stress, and improved insulin resistance in DIO mice, in concert with improvements in the insulin metabolic signaling, mitochondrial respiratory chain enzymatic activation, adenine nucleotide production, organism metabolism and weight gain. Results support the hypothesis that exenatide reduces hepatic cells and mitochondrial structural anomaly and improves insulin resistance in concert with improvements in insulin sensitivity and mitochondrial function activation, concomitantly with reductions in oxidative stress.

  3. Glycyrrhizic acid improved lipoprotein lipase expression, insulin sensitivity, serum lipid and lipid deposition in high-fat diet-induced obese rats

    PubMed Central

    2010-01-01

    Background The metabolic syndrome, known also as the insulin resistance syndrome, refers to the clustering of several risk factors for atherosclerotic cardiovascular disease. Dyslipidaemia is a hallmark of the syndrome and is associated with a whole body reduction in the activity of lipoprotein lipase (LPL), an enzyme under the regulation of the class of nuclear receptors known as peroxisome proliferator-activated receptor (PPAR). Glycyrrhizic acid (GA), a triterpenoid saponin, is the primary bioactive constituent of the roots of the shrub Glycyrrhiza glabra. Studies have indicated that triterpenoids could act as PPAR agonists and GA is therefore postulated to restore LPL expression in the insulin resistant state. Results Oral administration of 100 mg/kg of GA to high-fat diet-induced obese rats for 28 days led to significant reduction in blood glucose concentration and improvement in insulin sensitivity as indicated by the homeostasis model assessment of insulin resistance (HOMA-IR) (p < 0.05). LPL expression was up-regulated in the kidney, heart, quadriceps femoris, abdominal muscle and the visceral and subcutaneous adipose tissues but down-regulated in the liver - a condition in reverse to that seen in high-fat diet-induced obese rats without GA. With regard to lipid metabolism, GA administration led to significant hypotriglyceridemic and HDL-raising effects (p < 0.05), with a consistent reduction in serum free fatty acid, total cholesterol and LDL cholesterol and significant decrease in tissue lipid deposition across all studied tissue (p < 0.01). Conclusion In conclusion, GA may be a potential compound in improving dyslipidaemia by selectively inducing LPL expression in non-hepatic tissues. Such up-regulation was accompanied by a GA-mediated improvement in insulin sensitivity, which may be associated with a decrease in tissue lipid deposition. The HDL-raising effect of GA suggests the antiatherosclerotic properties of GA. PMID:20670429

  4. Femoral Bone Marrow Insulin Sensitivity Is Increased by Resistance Training in Elderly Female Offspring of Overweight and Obese Mothers

    PubMed Central

    Huovinen, Ville; Bucci, Marco; Lipponen, Heta; Kiviranta, Riku; Sandboge, Samuel; Raiko, Juho; Koskinen, Suvi; Koskensalo, Kalle; Eriksson, Johan G.; Parkkola, Riitta; Iozzo, Patricia; Nuutila, Pirjo

    2016-01-01

    Bone marrow insulin sensitivity may be an important factor for bone health in addition to bone mineral density especially in insulin resistant conditions. First we aimed to study if prenatal maternal obesity plays a role in determining bone marrow insulin sensitivity in elderly female offspring. Secondly we studied if a four-month individualized resistance training intervention increases bone marrow insulin sensitivity in elderly female offspring and whether this possible positive outcome is regulated by the offspring’s mother’s obesity status. 37 frail elderly females (mean age 71.9 ± 3.1 years) of which 20 were offspring of lean/normal-weight mothers (OLM, maternal BMI ≤ 26.3 kg/m2) and 17 were offspring of obese/overweight mothers (OOM, maternal BMI ≥ 28.1 kg/m2) were studied before and after a four-month individualized resistance training intervention. Nine age- and sex-matched non-frail controls (maternal BMI ≤ 26.3 kg/m2) were studied at baseline. Femoral bone marrow (FBM) and vertebral bone marrow (VBM) insulin sensitivity were measured using [18F]fluoro-2-deoxy-D-glucose positron emission tomography with computer tomography under hyperinsulinemic euglycemic clamp. We found that bone marrow insulin sensitivity was not related to maternal obesity status but FBM insulin sensitivity correlated with whole body insulin sensitivity (R = 0.487, p = 0.001). A four-month resistance training intervention increased FBM insulin sensitivity by 47% (p = 0.006) only in OOM, while VBM insulin sensitivity remained unchanged regardless of the maternal obesity status. In conclusion, FBM and VBM glucose metabolism reacts differently to a four-month resistance training intervention in elderly women according to their maternal obesity status. Trial Registration ClinicalTrials.gov NCT01931540 PMID:27669153

  5. Inherent insulin sensitivity is a major determinant of multimeric adiponectin responsiveness to short-term weight loss in extreme obesity.

    PubMed

    Mai, Stefania; Walker, Gillian E; Brunani, Amelia; Guzzaloni, Gabriele; Grossi, Glenda; Oldani, Alberto; Aimaretti, Gianluca; Scacchi, Massimo; Marzullo, Paolo

    2014-07-24

    High molecular weight (HMW-A) adiponectin levels mirror alterations in glucose homeostasis better than medium (MMW-A) and low molecular weight (LMW-A) components. In 25 patients with wide-range extreme obesity (BMI 40-77 kg/m(2)), we aimed to explore if improvements of multimeric adiponectin following 4-wk weight loss reflect baseline OGTT-derived insulin sensitivity (ISIOGTT) and disposition index (DIOGTT). Compared to 40 lean controls, adiponectin oligomers were lower in extreme obesity (p < 0.001) and, within this group, HMW-A levels were higher in insulin-sensitive (p < 0.05) than -resistant patients. In obese patients, short-term weight loss did not change total adiponectin levels and insulin resistance, while the distribution pattern of adiponectin oligomers changed due to significant increment of HMW-A (p < 0.01) and reduction of MMW-A (p < 0.05). By multivariate analysis, final HMW-A levels were significantly related to baseline ISIOGTT and final body weight (adjusted R(2) = 0.41). Our data suggest that HMW adiponectin may reflect baseline insulin sensitivity appropriately in the context of extreme obesity. Especially, we documented that HMW-A is promptly responsive to short-term weight loss prior to changes in insulin resistance, by a magnitude that is proportioned to whole body insulin sensitivity. This may suggest an insulin sensitivity-dependent control operated by HMW-A on metabolic dynamics of patients with extreme obesity.

  6. Diet-induced obesity and insulin resistance spur tumor growth and cancer cachexia in rats bearing the Yoshida sarcoma.

    PubMed

    Honors, Mary Ann; Kinzig, Kimberly P

    2014-01-01

    Obesity and insulin resistance are associated with increased risk of cancer and cancer mortality. However, it is currently unknown whether they contribute to the development of cancer cachexia, a syndrome that contributes significantly to morbidity and mortality in individuals with cancer. The present experiment addresses the question of whether preexisting obesity and insulin resistance alter tumor growth and cancer cachexia symptoms in Yoshida sarcoma bearing male rats. Obesity and insulin resistance were induced through 5 weeks of high-fat (HF) diet feeding and insulin resistance was confirmed by intraperitoneal glucose tolerance testing. Chow-fed animals were used as a control group. Following the establishment of insulin resistance, HF- and chow-fed animals were implanted with fragments of the Yoshida sarcoma or received a sham surgery. Tumor growth rate was greater in HF-fed animals, resulting in larger tumors. In addition, cancer cachexia symptoms developed in HF-fed animals but not chow-fed animals during the 18-day experiment. These results support a stimulatory effect of obesity and insulin resistance on tumor growth and cancer cachexia development in Yoshida sarcoma-bearing rats. Future research should investigate the relationship between obesity, insulin resistance, and cancer cachexia in human subjects.

  7. Association between insulin resistance and estrogen in sexual precocity of obese children

    PubMed Central

    Lin, Shixia; Ji, Wei

    2016-01-01

    The aim of the study was to examine the association between sexual precocity and high-molecular weight (HMW)-adiponectin and investigate the correlation of insulin resistance and estrogen levels in obese children. In total, 60 obese children (30 boys and 30 girls) with sexual precocity were included in group A, 60 obese children (30 boys and 30 girls) without sexual precocity were included in group B, and 60 average weight children (30 boys and 30 girls) were included in group C. The levels of HMW adiponectin, fasting blood glucose, fasting insulin, luteinizing hormone (LH) peak, estradiol and testosterone were measured. The results showed that the HMW-adiponectin level of group A was the lowest and that of group C was the highest. The difference was statistically significant (P<0.05). The homeostasis model assessment of insulin resistance (HOMA-IR) and estradiol levels of group A were significantly higher than those of group B, and group B was higher than that of group C. LH peak and testosterone levels of group A were the lowest while those of group C were the highest. The differences were statistically significant (P<0.05). A subgroup analysis showed that the above results were more significant in girls. The Pearson correlation analysis revealed that the level of HMW-adiponectin was negatively correlated with HOMA-IR and estradiol (P<0.05), and positively correlated with the LH peak (P<0.05). In conclusion, sexual precocity of obese children may be associated with insulin resistance, and the link may be HMW-adiponectin. PMID:27703507

  8. GH Receptor Deficiency in Ecuadorian Adults Is Associated With Obesity and Enhanced Insulin Sensitivity

    PubMed Central

    Rosenbloom, Arlan L.; Balasubramanian, Priya; Teran, Enrique; Guevara-Aguirre, Marco; Guevara, Carolina; Procel, Patricio; Alfaras, Irene; De Cabo, Rafael; Di Biase, Stefano; Narvaez, Luis; Saavedra, Jannette

    2015-01-01

    Context: Ecuadorian subjects with GH receptor deficiency (GHRD) have not developed diabetes, despite obesity. Objective: We sought to determine the metabolic associations for this phenomenon. Design: Four studies were carried out: 1) glucose, lipid, adipocytokine concentrations; 2) metabolomics evaluation; 3) metabolic responses to a high-calorie meal; and 4) oral glucose tolerance tests. Setting: Clinical Research Institute in Quito, Ecuador. Subjects: Adults homozygous for the E180 splice mutation of the GH receptor (GHRD) were matched for age, gender, and body mass index with unaffected control relatives (C) as follows: study 1, 27 GHRD and 35 C; study 2, 10 GHRD and 10 C; study 3, seven GHRD and 11 C; and study 4, seven GHRD and seven C. Results: Although GHRD subjects had greater mean percentage body fat than controls, their fasting insulin, 2-hour blood glucose, and triglyceride levels were lower. The indicator of insulin sensitivity, homeostasis model of assessment 2%S, was greater (P < .0001), and the indicator of insulin resistance, homeostasis model of assessment 2-IR, was lower (P = .0025). Metabolomic differences between GHRD and control subjects were consistent with their differing insulin sensitivity, including postprandial decreases of branched-chain amino acids that were more pronounced in controls. High molecular weight and total adiponectin concentrations were greater in GHRD (P = .0004 and P = .0128, respectively), and leptin levels were lower (P = .02). Although approximately 65% the weight of controls, GHRD subjects consumed an identical high-calorie meal; nonetheless, their mean glucose concentrations were lower, with mean insulin levels one-third those of controls. Results of the 2-hour oral glucose tolerance test were similar. Main Outcome Measures: Measures of insulin sensitivity, adipocytokines, and energy metabolites. Conclusions: Without GH counter-regulation, GHRD is associated with insulin efficiency and obesity. Lower leptin levels

  9. Inflammation and Oxidative Stress: The Molecular Connectivity between Insulin Resistance, Obesity, and Alzheimer's Disease

    PubMed Central

    Verdile, Giuseppe; Keane, Kevin N.; Cruzat, Vinicius F.; Medic, Sandra; Sabale, Miheer; Rowles, Joanne; Wijesekara, Nadeeja; Martins, Ralph N.; Fraser, Paul E.; Newsholme, Philip

    2015-01-01

    Type 2 diabetes (T2DM), Alzheimer's disease (AD), and insulin resistance are age-related conditions and increased prevalence is of public concern. Recent research has provided evidence that insulin resistance and impaired insulin signalling may be a contributory factor to the progression of diabetes, dementia, and other neurological disorders. Alzheimer's disease (AD) is the most common subtype of dementia. Reduced release (for T2DM) and decreased action of insulin are central to the development and progression of both T2DM and AD. A literature search was conducted to identify molecular commonalities between obesity, diabetes, and AD. Insulin resistance affects many tissues and organs, either through impaired insulin signalling or through aberrant changes in both glucose and lipid (cholesterol and triacylglycerol) metabolism and concentrations in the blood. Although epidemiological and biological evidence has highlighted an increased incidence of cognitive decline and AD in patients with T2DM, the common molecular basis of cell and tissue dysfunction is rapidly gaining recognition. As a cause or consequence, the chronic inflammatory response and oxidative stress associated with T2DM, amyloid-β (Aβ) protein accumulation, and mitochondrial dysfunction link T2DM and AD. PMID:26693205

  10. Inverse regulation of inflammation and mitochondrial function in adipose tissue defines extreme insulin sensitivity in morbidly obese patients.

    PubMed

    Qatanani, Mohammed; Tan, Yejun; Dobrin, Radu; Greenawalt, Danielle M; Hu, Guanghui; Zhao, Wenqing; Olefsky, Jerrold M; Sears, Dorothy D; Kaplan, Lee M; Kemp, Daniel M

    2013-03-01

    Obesity is associated with insulin resistance, a major risk factor for type 2 diabetes and cardiovascular disease. However, not all obese individuals are insulin resistant, which confounds our understanding of the mechanistic link between these conditions. We conducted transcriptome analyses on 835 obese subjects with mean BMI of 48.8, on which we have previously reported genetic associations of gene expression. Here, we selected ~320 nondiabetic (HbA(1c) <7.0) subjects and further stratified the cohort into insulin-resistant versus insulin-sensitive subgroups based on homeostasis model assessment-insulin resistance. An unsupervised informatics analysis revealed that immune response and inflammation-related genes were significantly downregulated in the omental adipose tissue of obese individuals with extreme insulin sensitivity and, to a much lesser extent, in subcutaneous adipose tissue. In contrast, genes related to β-oxidation and the citric acid cycle were relatively overexpressed in adipose of insulin-sensitive patients. These observations were verified by querying an independent cohort of our published dataset of 37 subjects whose subcutaneous adipose tissue was sampled before and after treatment with thiazolidinediones. Whereas the immune response and inflammation pathway genes were downregulated by thiazolidinedione treatment, β-oxidation and citric acid cycle genes were upregulated. This work highlights the critical role that omental adipose inflammatory pathways might play in the pathophysiology of insulin resistance, independent of body weight.

  11. Disturbances of basal and postprandial insulin secretion and clearance in obese patients with type 2 diabetes mellitus.

    PubMed

    Erdmann, J; Pöhnl, K; Mayr, M; Sypchenko, O; Naumann, A; Wagenpfeil, S; Schusdziarra, V

    2012-01-01

    Hyperinsulinemia of nondiabetic overweight and obese subjects is associated with weight-dependent increased insulin secretion and decreased insulin clearance. The present analysis examines whether similar effects can be observed in overweight and obese patients with type 2 diabetes mellitus (DM2). Additionally basal and postprandial insulin secretion and clearance were analyzed in relation to duration of disease. In a random sample of 348 DM2 patients basal plasma insulin concentrations were significantly higher in most BMI groups compared to matched nondiabetic (ND) controls. The weight-dependent increase of basal insulin in DM2 was primarily the result of reduced clearance rather than augmented secretion. Postprandial insulin concentrations were lower in DM2 patients and did not show any BMI-related increase. The weight-dependent reduction of postprandial insulin clearance was absent in DM2. At the time of diagnosis basal insulin concentration was higher and secretion was comparable to ND subjects and this did not change with duration of diabetes. The early postprandial insulin response was still comparable between DM2 and ND subjects at the time of diagnosis but deteriorated with longer duration of disease. The later postprandial response at diagnosis (AUC 90-180) was characterized by significantly greater insulin secretion and concentration while later on the 3-fold higher secretion was paralleled by comparable peripheral plasma concentrations due to a significantly greater postprandial insulin clearance in DM2. In conclusion, the present data indicate that apart from disturbances of insulin secretion substantial changes of insulin clearance contribute to inadequate peripheral insulin concentrations in obese DM2 patients.

  12. Insulin resistance in prepubertal obese children correlates with sex-dependent early onset metabolomic alterations

    PubMed Central

    Mastrangelo, A; Martos-Moreno, G Á; García, A; Barrios, V; Rupérez, F J; Chowen, J A; Barbas, C; Argente, J

    2016-01-01

    Background: Insulin resistance (IR) is usually the first metabolic alteration diagnosed in obese children and the key risk factor for development of comorbidities. The factors determining whether or not IR develops as a result of excess body mass index (BMI) are still not completely understood. Objectives: This study aimed to elucidate the mechanisms underpinning the predisposition toward hyperinsulinemia-related complications in obese children by using a metabolomic strategy that allows a profound interpretation of metabolic profiles potentially affected by IR. Methods: Serum from 60 prepubertal obese children (30 girls/30 boys, 50% IR and 50% non-IR in each group, but with similar BMIs) were analyzed by using liquid chromatography–mass spectrometry, gas chromatography–mass spectrometry and capillary electrophoresis–mass spectrometry following an untargeted metabolomics approach. Validation was then performed on a group of 100 additional children with the same characteristics. Results: When obese children with and without IR were compared, 47 metabolites out of 818 compounds (P<0.05) obtained after data pre-processing were found to be significantly different. Bile acids exhibit the greatest changes (that is, approximately a 90% increase in IR). The majority of metabolites differing between groups were lysophospholipids (15) and amino acids (17), indicating inflammation and central carbon metabolism as the most altered processes in impaired insulin signaling. Multivariate analysis (OPLS-DA models) showed subtle differences between groups that were magnified when females were analyzed alone. Conclusions: Inflammation and central carbon metabolism, together with the contribution of the gut microbiota, are the most altered processes in obese children with impaired insulin signaling in a sex-specific fashion despite their prepubertal status. PMID:27163744

  13. Alternative (M2) activation of Kupffer cells by PPARδ ameliorates obesity-induced insulin resistance

    PubMed Central

    Odegaard, Justin I.; Ricardo-Gonzalez, Roberto R.; Eagle, Alex Red; Vats, Divya; Morel, Christine R.; Goforth, Matthew H.; Subramanian, Vidya; Mukundan, Lata; Ferrante, Anthony W.; Chawla, Ajay

    2008-01-01

    SUMMARY Macrophage infiltration and activation in metabolic tissues underlie obesity-induced insulin resistance and type 2 diabetes. While inflammatory activation of resident hepatic macrophages potentiates insulin resistance, the functions of alternatively activated Kupffer cells in metabolic disease remain unknown. Here we show that, in response to the Th2 cytokine interleukin-4 (IL-4), peroxisome proliferator activated receptor δ (PPARδ) directs expression of the alternative phenotype in Kupffer cells and adipose tissue macrophages of lean mice. However, adoptive transfer of PPARδ null bone marrow into wild type mice only diminishes alternative activation of hepatic macrophages, causing hepatic dysfunction and systemic insulin resistance. Suppression of hepatic oxidative metabolism is recapitulated by treatment of primary hepatocytes with conditioned media from PPARδ null macrophages, indicating direct involvement of Kupffer cells in liver lipid metabolism. Taken together, these data suggest an unexpected beneficial role for alternatively activated Kupffer cells in metabolic syndrome and type 2 diabetes. PMID:18522831

  14. Compensatory hyperinsulinemia in high-fat diet-induced obese mice is associated with enhanced insulin translation in islets

    SciTech Connect

    Kanno, Ayumi; Asahara, Shun-ichiro; Masuda, Katsuhisa; Matsuda, Tomokazu; Kimura-Koyanagi, Maki; Seino, Susumu; Ogawa, Wataru; Kido, Yoshiaki

    2015-03-13

    A high-fat diet (HF) is associated with obesity, insulin resistance, and hyperglycemia. Animal studies have shown compensatory mechanisms in pancreatic β-cells after high fat load, such as increased pancreatic β-cell mass, enhanced insulin secretion, and exocytosis. However, the effects of high fat intake on insulin synthesis are obscure. Here, we investigated whether insulin synthesis was altered in correlation with an HF diet, for the purpose of obtaining further understanding of the compensatory mechanisms in pancreatic β-cells. Mice fed an HF diet are obese, insulin resistant, hyperinsulinemic, and glucose intolerant. In islets of mice fed an HF diet, more storage of insulin was identified. We analyzed insulin translation in mouse islets, as well as in INS-1 cells, using non-radioisotope chemicals. We found that insulin translational levels were significantly increased in islets of mice fed an HF diet to meet systemic demand, without altering its transcriptional levels. Our data showed that not only increased pancreatic β-cell mass and insulin secretion but also elevated insulin translation is the major compensatory mechanism of pancreatic β-cells. - Highlights: • More stored insulin was recognized in islets of mice fed a high-fat diet. • Insulin translation was not enhanced by fatty acids, but by insulin demand. • Insulin transcription was not altered in islets of mice fed a high-fat diet. • Insulin translation was markedly enhanced in islets of mice fed a high-fat diet. • Non-radioisotope chemicals were used to measure insulin translation in mouse islets.

  15. NOV/CCN3: A New Adipocytokine Involved in Obesity-Associated Insulin Resistance.

    PubMed

    Martinerie, Cécile; Garcia, Marie; Do, Thi Thu Huong; Antoine, Bénédicte; Moldes, Marthe; Dorothee, Guillaume; Kazazian, Chantal; Auclair, Martine; Buyse, Marion; Ledent, Tatiana; Marchal, Pierre-Olivier; Fesatidou, Maria; Beisseiche, Adrien; Koseki, Haruhiko; Hiraoka, Shuichi; Chadjichristos, Christos Evangelos; Blondeau, Bertrand; Denis, Raphael Georges; Luquet, Serge; Fève, Bruno

    2016-09-01

    Identification of new adipokines that potentially link obesity to insulin resistance represents a major challenge. We recently showed that NOV/CCN3, a multifunctional matricellular protein, is synthesized and secreted by adipose tissue, with plasma levels highly correlated with BMI. NOV involvement in tissue repair, fibrotic and inflammatory diseases, and cancer has been previously reported. However, its role in energy homeostasis remains unknown. We investigated the metabolic phenotype of NOV(-/-) mice fed a standard or high-fat diet (HFD). Strikingly, the weight of NOV(-/-) mice was markedly lower than that of wild-type mice but only on an HFD. This was related to a significant decrease in fat mass associated with an increased proportion of smaller adipocytes and to a higher expression of genes involved in energy expenditure. NOV(-/-) mice fed an HFD displayed improved glucose tolerance and insulin sensitivity. Interestingly, the absence of NOV was associated with a change in macrophages profile (M1-like to M2-like), in a marked decrease in adipose tissue expression of several proinflammatory cytokines and chemokines, and in enhanced insulin signaling. Conversely, NOV treatment of adipocytes increased chemokine expression. Altogether, these results show that NOV is a new adipocytokine that could be involved in obesity-associated insulin-resistance.

  16. Obesity increases the odds of acquiring and incarcerating noninguinal abdominal wall hernias.

    PubMed

    Lau, Briana; Kim, Hanjoo; Haigh, Philip I; Tejirian, Talar

    2012-10-01

    The current data available describing the relationship of obesity and abdominal wall hernias is sparse. The objective of this study was to investigate the current prevalence of noninguinal abdominal wall hernias and their correlation with body mass index (BMI) and other demographic risk factors. Patients with umbilical, incisional, ventral, epigastric, or Spigelian hernias with or without incarceration were identified using the regional database for 14 hospitals over a 3-year period. Patients were stratified based on their BMI. Univariate and multivariate analyses were performed to distinguish other significant risk factors associated with the hernias. Of 2,807,414 patients, 26,268 (0.9%) had one of the specified diagnoses. Average age of the patients was 52 years and 61 per cent were male. The majority of patients had nonincarcerated umbilical hernias (74%). Average BMI was 32 kg/m2. Compared with patients with a normal BMI, the odds of having a hernia increased with BMI: BMI of 25 to 29.9 kg/m2 odds ratio (OR) 1.63, BMI of 30 to 39.9 kg/m2 OR 2.62, BMI 40 to 49.9 kg/m2 OR 3.91, BMI 50 to 59.9 kg/m2 OR 4.85, and BMI greater than 60 kg/m2 OR 5.17 (P<0.0001). Age older than 50 years was associated with a higher risk for having a hernia (OR, 2.12; 95% [CI], 2.07 to 2.17), whereas female gender was associated with a lower risk (OR, 0.53; 95% CI, 0.52 to 0.55). Those with incarcerated hernias had a higher average BMI (32 kg/m2 vs 35 kg/m2; P<0.0001). Overall, BMI greater than 40 kg/m2 showed an increased chance of incarceration, and a BMI greater than 60 kg/m2 had the highest chance of incarceration, OR 12.7 (P<0.0001). Age older than 50 years and female gender were also associated with a higher risk of incarceration (OR, 1.28; 95% CI, 1.02 to 1.59 and OR, 1.80; CI, 1.45 to 2.24). Increasing BMI and increasing age are associated with a higher prevalence and an increased risk of incarceration of noninguinal abdominal wall hernias.

  17. Vitamin E and vitamin C do not reduce insulin sensitivity but inhibit mitochondrial protein expression in exercising obese rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Controversy exists as to whether supplementation with the antioxidants vitamin E (VE) and vitamin C (VC) blocks adaptation to exercise. Exercise is a first-line means to treat obesity and its complications. While diet-induced obesity alters mitochondrial (MT) function and induces insulin resistance ...

  18. Associations of Diabetes and Obesity with Risk of Abdominal Aortic Aneurysm in Men

    PubMed Central

    Djousse, Luc; Song, Yiqing; Akinkuolie, Akintunde O.; Matsumoto, Chisa; Manson, JoAnn E.; Gaziano, J. Michael; Sesso, Howard D.

    2017-01-01

    Background. The associations of diabetes and obesity with the risk of abdominal aortic aneurysm (AAA) are inconclusive in previous studies. Subjects/Methods. We conducted prospective analysis in the Physicians' Health Study. Among 25,554 male physicians aged ≥ 50 years who reported no AAA at baseline, 471 reported a newly diagnosed AAA during a mean of 10.4 years' follow-up. Results. Compared with men who had baseline body mass index (BMI) < 25 kg/m2, the multivariable hazard ratio (HR [95% CI]) of newly diagnosed AAA was 1.30 [1.06–1.59] for BMI 25–<30 kg/m2 and 1.69 [1.24–2.30] for BMI ≥ 30 kg/m2. The risk of diagnosed AAA was significantly higher by 6% with each unit increase in baseline BMI. This association was consistent regardless of the other known AAA risk factors and preexisting vascular diseases. Overall, baseline history of diabetes tended to be associated with a lower risk of diagnosed AAA (HR = 0.79 [0.57–1.11]); this association appeared to vary by follow-up time (HR = 1.56 and 0.63 during ≤ and >2 years' follow-up, resp.). Conclusion. In a large cohort of middle-aged and older men, obesity was associated with a higher risk, while history of diabetes tended to associate with a lower risk of diagnosed AAA, particularly over longer follow-up. PMID:28326193

  19. Lower resting and total energy expenditure in postmenopausal compared with premenopausal women matched for abdominal obesity.

    PubMed

    Hodson, Leanne; Harnden, Karin; Banerjee, Rajarshi; Real, Belen; Marinou, Kyriakoula; Karpe, Fredrik; Fielding, Barbara A

    2014-01-01

    The menopause is accompanied by increased risk of obesity, altered body fat distribution and decreased skeletal muscle mass. The resulting decrease in RMR should be accompanied by a compensatory change in energy balance to avoid weight gain. We aimed to investigate habitual energy intake and expenditure in pre- and postmenopausal women matched for abdominal obesity. We recruited fifty-one healthy Caucasian women, BMI > 18·5 and <35 kg/m(2), aged 35-45 years (premenopausal, n 26) and 55-65 years (postmenopausal, n 25). Energy intake was measured using 3 d diet diaries and dietary fat quality assessed using adipose tissue fatty acid biomarkers. RMR was measured using indirect calorimetry, and total energy expenditure (TEE) and activity energy expenditure using a combined accelerometer and heart rate monitor. Postmenopausal women had lower RMR and TEE and spent significantly less time undertaking moderate exercise than premenopausal women. Postmenopausal women had a tendency for a lower energy intake, and a similar macronutrient intake but a significantly lower adipose tissue n-6:n-3 ratio (24·6 (se 1·6) v. 37·7 (se 3·1); P < 0·001). The main lifestyle determinant of bone mineral density (which was significantly lower in postmenopausal women) was TEE for premenopausal women, and dietary n-6:n-3 ratio for postmenopausal women. The present results suggest that weight maintenance is achieved in the post- compared with premenopausal status through a combination of reduced energy intake and reduced TEE in a regimen that compromises micronutrient intake and has a negative impact on lean tissue mass. However, lower n-6:n-3 fatty acid intake in postmenopausal women is associated with greater bone mineral density.

  20. Artemisia extracts activate PPARγ, promote adipogenesis, and enhance insulin sensitivity in adipose tissue of obese mice

    PubMed Central

    Richard, Allison J.; Burris, Thomas P.; Sanchez-Infantes, David; Wang, Yongjun; Ribnicky, David M.; Stephens, Jacqueline M.

    2014-01-01

    Objective Studies have shown that the inability of adipose tissue to properly expand during the obese state or respond to insulin can lead to metabolic dysfunction. Artemisia is a diverse group of plants that has a history of medicinal use. This study examines the ability of ethanolic extracts of Artemisia scoparia (SCO) and Artemisia santolinifolia (SAN) to modulate adipocyte development in cultured adipocytes and white adipose tissue (WAT) function in vivo using a mouse model of diet-induced obesity. Research Design & Procedures Adipogenesis was assessed using Oil Red O staining and immunoblotting. A nuclear receptor specificity assay was used to examine the specificity of SCO- and SAN-induced PPARγ activation. C57BL/6J mice, fed a high-fat diet, were gavaged with saline, SCO, or SAN for 2 weeks. Whole-body insulin sensitivity was examined using insulin tolerance tests. WAT depots were assessed via immunoblotting for markers of insulin action and adipokine production. Results We established that SCO and SAN were highly specific activators of PPARγ and did not activate other nuclear receptors. After a one-week daily gavage, SCO- and SAN-treated mice had lower insulin-induced glucose disposal rates than control mice. At the end of the 2-week treatment period, SCO- and SAN-treated mice had enhanced insulin-responsive Akt serine-473 phosphorylation and significantly decreased MCP-1 levels in visceral WAT relative to control mice; these differences were depot specific. Moreover, plasma adiponectin levels were increased following SCO treatment. Conclusion Overall, these studies demonstrate that extracts from two Artemisia species can have metabolically favorable effects on adipocytes and WAT. PMID:24985103

  1. Insulin resistance is associated with specific gut microbiota in appendix samples from morbidly obese patients

    PubMed Central

    Moreno-Indias, Isabel; Sánchez-Alcoholado, Lidia; García-Fuentes, Eduardo; Cardona, Fernando; Queipo-Ortuño, Maria Isabel; Tinahones, Francisco J

    2016-01-01

    Alterations in intestinal microbiota composition could promote a proinflammatory state in adipose tissue that is associated with obesity and insulin resistance. Our aim was to identify the gut microbiota associated with insulin resistance in appendix samples from morbidly obese patients classified in 2 groups, high (IR-MO) and low insulin-resistant (NIR-MO), and to determine the possible association between these gut microbiota and variables associated with insulin resistance and the expression of genes related to inflammation and macrophage infiltration in adipose tissue. Appendix samples were obtained during gastric bypass surgery and the microbiome composition was determined by 16S rRNA pyrosequencing and bioinformatics analysis by QIIME. The Chao and Shannon indices for each study group suggested similar bacterial richness and diversity in the appendix samples between both study groups. 16S rRNA pyrosequencing showed that the IR-MO group had a significant increase in the abundance of Firmicutes, Fusobacteria, Pseudomonaceae, Prevotellaceae, Fusobacteriaceae, Pseudomonas, Catenibacterium, Prevotella, Veillonella and Fusobacterium compared to the NIR-MO group. Moreover, in the IR-MO group we found a significant positive correlation between the abundance of Prevotella, Succinovibrio, Firmicutes and Veillonella and the visceral adipose tissue expression level of IL6, TNF alpha, ILB1 and CD11b respectively, and significant negative correlations between the abundance of Butyricimonas and Bifidobacterium, and plasma glucose and insulin levels, respectively. In conclusion, an appendix dysbiosis occurs in IR-MO patients, with a loss of butyrate-producing bacteria, essential to maintenance of gut integrity, together with an increase in mucin-degrading bacteria and opportunistic pathogens. The microbiota present in the IR-MO group were related to low grade inflammation in adipose tissue and could be useful for developing strategies to control the development of insulin

  2. Endogenous epinephrine protects against obesity induced insulin resistance.

    PubMed

    Ziegler, Michael G; Milic, Milos; Sun, Ping; Tang, Chih-Min; Elayan, Hamzeh; Bao, Xuping; Cheung, Wai Wilson; O'Connor, Daniel T

    2011-07-05

    Epinephrine (E) is a hormone released from the adrenal medulla in response to low blood sugar and other stresses. E and related β2-adrenergic agonists are used to treat asthma, but a side effect is high blood sugar. C57BL/6 mice prone to overfeeding induced type II diabetes had the PNMT gene knocked out to prevent E synthesis. These E deficient mice were very similar to control animals on a 14% fat diet. On a 40.6% fat diet they gained 20 to 33% more weight than control animals and increased their blood glucose response to a glucose tolerance test because they became resistant to insulin. Although the short term effect of β2-agonists such as E is to raise blood glucose, some long acting β2-agonists improve muscle glucose uptake. Endogenous E protects against overfeeding induced diabetes. Since adrenal E release can be impaired with aging and diabetes, endogenous E may help prevent adult onset diabetes.

  3. Chronic Low-Calorie Sweetener Use and Risk of Abdominal Obesity among Older Adults: A Cohort Study

    PubMed Central

    Chia, Chee W.; Shardell, Michelle; Tanaka, Toshiko; Liu, David D.; Gravenstein, Kristofer S.; Simonsick, Eleanor M.

    2016-01-01

    Introduction Low-calorie sweetener use for weight control has come under increasing scrutiny as obesity, especially abdominal obesity, remain entrenched despite substantial low-calorie sweetener use. We evaluated whether chronic low-calorie sweetener use is a risk factor for abdominal obesity. Participants and Methods We used 8268 anthropometric measurements and 3096 food diary records with detailed information on low-calorie sweetener consumption in all food products, from 1454 participants (741 men, 713 women) in the Baltimore Longitudinal Study of Aging collected from 1984 to 2012 with median follow-up of 10 years (range: 0–28 years). At baseline, 785 were low-calorie sweetener non-users (51.7% men) and 669 participants were low-calorie sweetener users (50.1% men). Time-varying low-calorie sweetener use was operationalized as the proportion of visits since baseline at which low-calorie sweetener use was reported. We used marginal structural models to determine the association between baseline and time-varying low-calorie sweetener use with longitudinal outcomes—body mass index, waist circumference, obesity and abdominal obesity—with outcome status assessed at the visit following low-calorie sweetener ascertainment to minimize the potential for reverse causality. All models were adjusted for year of visit, age, sex, age by sex interaction, race, current smoking status, dietary intake (caffeine, fructose, protein, carbohydrate, and fat), physical activity, diabetes status, and Dietary Approaches to Stop Hypertension score as confounders. Results With median follow-up of 10 years, low-calorie sweetener users had 0.80 kg/m2 higher body mass index (95% confidence interval [CI], 0.17–1.44), 2.6 cm larger waist circumference (95% CI, 0.71–4.39), 36.7% higher prevalence (prevalence ratio = 1.37; 95% CI, 1.10–1.69) and 53% higher incidence (hazard ratio = 1.53; 95% CI 1.10–2.12) of abdominal obesity than low-calorie sweetener non-users. Conclusions Low

  4. Evaluation of neck circumference as a predictor of central obesity and insulin resistance in Chinese adults

    PubMed Central

    Wang, Xuhong; Zhang, Ning; Yu, Caiguo; Ji, Zhili

    2015-01-01

    Objectives: To evaluate whether neck circumference (NC) could be used as a valid and effective method for identifying obesity and insulin resistance (IR) in Chinese adults. Methods: A total of 3307 adults aged 20-65 years were randomly recruited from two communities of Tongzhou, Beijing. Height, weight, waist circumference (WC), hip circumference (HC), neck circumference (NC), blood pressure, fasting plasma glucose (FPG), fasting serum insulin (FINS), total cholesterol (TC), serum triglyceride (TG), High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and Urinary albumin (UAlb) were measured. Pearson correlation coefficient was used to explore the relationship between NC and other measurements. Furthermore, the best cutoff values of NC for central obesity identification were determined by applying the receiver operating characteristic (ROC) curve analysis. Results: NC correlated positively with BMI, SBP and WC In both sexes. Both WC and NC correlated significantly positively with IR. A positive correlation between NC and FPG as well as a negative correlation between NC and HDL were found in obese men. NC≥38.5 cm for men and ≥34.5 cm for women were determined to be the best cutoff levels for identifying subjects with central obesity, with 82.9% accuracy for men and 79.9% accuracy for women. Conclusions: NC correlated positively with BMI and WC in both genders, indicating that NC could be used as a valid marker for both overall obesity and central obesity. In addition, measuring NC was shown to be a useful test for IR identification. Large number of NC is suggested to be associated with high risk of developing metabolic disorders, such as diabetes and dyslipidemia. PMID:26770540

  5. Associations of vitamin D with insulin resistance, obesity, type 2 diabetes, and metabolic syndrome.

    PubMed

    Wimalawansa, Sunil J

    2016-09-20

    The aim of this study is to determine the relationships of vitamin D with diabetes, insulin resistance obesity, and metabolic syndrome. Intra cellular vitamin D receptors and the 1-α hydroxylase enzyme are distributed ubiquitously in all tissues suggesting a multitude of functions of vitamin D. It plays an indirect but an important role in carbohydrate and lipid metabolism as reflected by its association with type 2 diabetes (T2D), metabolic syndrome, insulin secretion, insulin resistance, polycystic ovarian syndrome, and obesity. Peer-reviewed papers, related to the topic were extracted using key words, from PubMed, Medline, and other research databases. Correlations of vitamin D with diabetes, insulin resistance and metabolic syndrome were examined for this evidence-based review. In addition to the well-studied musculoskeletal effects, vitamin D decreases the insulin resistance, severity of T2D, prediabetes, metabolic syndrome, inflammation, and autoimmunity. Vitamin D exerts autocrine and paracrine effects such as direct intra-cellular effects via its receptors and the local production of 1,25(OH)2D3, especially in muscle and pancreatic β-cells. It also regulates calcium homeostasis and calcium flux through cell membranes, and activation of a cascade of key enzymes and cofactors associated with metabolic pathways. Cross-sectional, observational, and ecological studies reported inverse correlations between vitamin D status with hyperglycemia and glycemic control in patients with T2D, decrease the rate of conversion of prediabetes to diabetes, and obesity. However, no firm conclusions can be drawn from current studies, because (A) studies were underpowered; (B) few were designed for glycemic outcomes, (C) the minimum (or median) serum 25(OH) D levels achieved are not measured or reported; (D) most did not report the use of diabetes medications; (E) some trials used too little (F) others used too large, unphysiological and infrequent doses of vitamin D; and (G

  6. Measurement of waist circumference at different sites affects the detection of abdominal obesity and metabolic syndrome among psychiatric patients.

    PubMed

    Lin, Chao-Cheng; Yu, Shun-Chieh; Wu, Bo-Jian; Chang, Da-Jen

    2012-05-30

    There is a lack of understanding about the impact of different waist circumference (WC) measurements on the detection of abdominal obesity and metabolic syndrome in psychiatric patients. This cross-sectional study included a total of 382 inpatients with schizophrenia-related disorders to assess each component of metabolic syndrome. WC was measured at the lowest rib, midpoint between the iliac crest and lowest rib, iliac crest, minimal waist, and umbilicus. Logistic regression analysis was performed to examine the ability of WC at each site to predict the presence of metabolic risk clustering. The mean WC values for all sites were significantly different from each other. The measurement site had an influence on the prevalence of abdominal obesity (30-38.2% in men and 53.9-86.3% in women). The influence on the prevalence of metabolic syndrome was greater with the International Diabetes Federation (IDF) criteria (19.3-23.9% in men and 29.4-43.1% in women) than with the Adult Treatment Panel III (ATP III) criteria (26.1-28.6% in men and 37.3-44.1% in women). The areas under the receiver operating characteristic curve for metabolic risk clustering were highest at the umbilicus and midpoint. Given that the WC measurement protocol has substantial influence on the prevalence of abdominal obesity and metabolic syndrome, a predefined measurement site is required for all psychiatric studies.

  7. Optimal Definitions for Abdominal Obesity and the Metabolic Syndrome in Andean Hispanics: The PREVENCION Study

    PubMed Central

    Medina-Lezama, Josefina; Pastorius, Catherine A.; Zea-Diaz, Humberto; Bernabe-Ortiz, Antonio; Corrales-Medina, Fernando; Morey-Vargas, Oscar Leopoldo; Chirinos, Diana Andrea; Muñoz-Atahualpa, Edgar; Chirinos-Pacheco, Julio; Chirinos, Julio Alonso

    2010-01-01

    OBJECTIVE We aimed to establish optimal definitions for abdominal obesity and metabolic syndrome (MetS) among Andean adults. RESEARCH DESIGN AND METHODS Among 1,448 Andean adults, we assessed the relationship between waist circumference and subclinical vascular disease assessed by carotid intima-media thickness (cIMT) and manifest cardiovascular disease (M-CVD). RESULTS Optimal waist circumference cutoffs to classify individuals with abnormal cIMT or M-CVD were >97 and >87 cm in men and women, respectively. With these cutoffs, there was substantial disagreement between the original American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) and the recently updated MetS definition, particularly among men (κ = 0.85). Subjects with MetS identified by the updated definition but not meeting the original AHA/NHLBI MetS criteria demonstrated significantly increased cIMT (P < 0.001) compared with subjects who did not meet the MetS criteria by either definition. CONCLUSIONS Our findings support the use of ethnic-specific waist circumference cutoffs and the updated MetS definition in Andean adults. PMID:20200303

  8. Gastroesophageal reflux symptoms in Turkish people: a positive correlation with abdominal obesity in women

    PubMed Central

    Karayaka, Sergul; Mesci, Banu; Oguz, Aytekin; Tamer, Gonca

    2015-01-01

    OBJECTIVE: Metabolic syndrome (MetS) is increasing around the world due to abdominal obesity with altered eating habits and decreased physical activity. The aim of this study was to determine the risk factors for gastroesophagial reflux disease (GERD) symptoms and the prevalence of GERD in patients with MetS. METHODS: Five hundred patients (MetS, n=300 and the control group, n=200) were enrolled in the study. A detailed questionnaire reflux symptoms and behavioral habits was performed. RESULTS: Sixty percent of the subjects were with MetS. GERD rate was significantly higher in the group with MetS compared to subjects without MetS (50.7% vs 26%). Women were more likely to have GERD in both groups (62.6% of women and 28.6% of men ın the MetS group while corresponding rates were 37% vs 16.7% in the control group). Waist circumferences were found to be higher in female MetS patients with GERD. CONCLUSION: GERD is present approximately in every one of the two patients with MetS. Every patient who has MetS should be evaluated in terms of GERD symptoms. PMID:28058320

  9. Effects of a multidisciplinary body weight reduction program on static and dynamic thoraco-abdominal volumes in obese adolescents.

    PubMed

    LoMauro, Antonella; Cesareo, Ambra; Agosti, Fiorenza; Tringali, Gabriella; Salvadego, Desy; Grassi, Bruno; Sartorio, Alessandro; Aliverti, Andrea

    2016-06-01

    The objective of this study was to characterize static and dynamic thoraco-abdominal volumes in obese adolescents and to test the effects of a 3-week multidisciplinary body weight reduction program (MBWRP), entailing an energy-restricted diet, psychological and nutritional counseling, aerobic physical activity, and respiratory muscle endurance training (RMET), on these parameters. Total chest wall (VCW), pulmonary rib cage (VRC,p), abdominal rib cage (VRC,a), and abdominal (VAB) volumes were measured on 11 male adolescents (Tanner stage: 3-5; BMI standard deviation score: >2; age: 15.9 ± 1.3 years; percent body fat: 38.4%) during rest, inspiratory capacity (IC) maneuver, and incremental exercise on a cycle ergometer at baseline and after 3 weeks of MBWRP. At baseline, the progressive increase in tidal volume was achieved by an increase in end-inspiratory VCW (p < 0.05) due to increases in VRC,p and VRC,a with constant VAB. End-expiratory VCW decreased with late increasing VRC,p, dynamically hyperinflating VRC,a (p < 0.05), and progressively decreasing VAB (p < 0.05). After MBWRP, weight loss was concentrated in the abdomen and total IC decreased. During exercise, abdominal rib cage hyperinflation was delayed and associated with 15% increased performance and reduced dyspnea at high workloads (p < 0.05) without ventilatory and metabolic changes. We conclude that otherwise healthy obese adolescents adopt a thoraco-abdominal operational pattern characterized by abdominal rib cage hyperinflation as a form of lung recruitment during incremental cycle exercise. Additionally, a short period of MBWRP including RMET is associated with improved exercise performance, lung and chest wall volume recruitment, unloading of respiratory muscles, and reduced dyspnea.

  10. General and abdominal obesity and risk of esophageal and gastric adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition.

    PubMed

    Steffen, Annika; Huerta, José-Maria; Weiderpass, Elisabete; Bueno-de-Mesquita, H B As; May, Anne M; Siersema, Peter D; Kaaks, Rudolf; Neamat-Allah, Jasmine; Pala, Valeria; Panico, Salvatore; Saieva, Calogero; Tumino, Rosario; Naccarati, Alessio; Dorronsoro, Miren; Sánchez-Cantalejo, Emilio; Ardanaz, Eva; Quirós, J Ramón; Ohlsson, Bodil; Johansson, Mattias; Wallner, Bengt; Overvad, Kim; Halkjaer, Jytte; Tjønneland, Anne; Fagherazzi, Guy; Racine, Antoine; Clavel-Chapelon, Françoise; Key, Tim J; Khaw, Kay-Tee; Wareham, Nick; Lagiou, Pagona; Bamia, Christina; Trichopoulou, Antonia; Ferrari, Pietro; Freisling, Heinz; Lu, Yunxia; Riboli, Elio; Cross, Amanda J; Gonzalez, Carlos A; Boeing, Heiner

    2015-08-01

    General obesity, as reflected by BMI, is an established risk factor for esophageal adenocarcinoma (EAC), a suspected risk factor for gastric cardia adenocarcinoma (GCC) and appears unrelated to gastric non-cardia adenocarcinoma (GNCC). How abdominal obesity, as commonly measured by waist circumference (WC), relates to these cancers remains largely unexplored. Using measured anthropometric data from 391,456 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and 11 years of follow-up, we comprehensively assessed the association of anthropometric measures with risk of EAC, GCC and GNCC using multivariable proportional hazards regression. One hundred twenty-four incident EAC, 193 GCC and 224 GNCC were accrued. After mutual adjustment, BMI was unrelated to EAC, while WC showed a strong positive association (highest vs. lowest quintile HR = 1.19; 95% CI, 0.63-2.22 and HR = 3.76; 1.72-8.22, respectively). Hip circumference (HC) was inversely related to EAC after controlling for WC, while WC remained positively associated (HR = 0.35; 0.18-0.68, and HR=4.10; 1.94-8.63, respectively). BMI was not associated with GCC or GNCC. WC was related to higher risks of GCC after adjustment for BMI and more strongly after adjustment for HC (highest vs. lowest quintile HR = 1.91; 1.09-3.37, and HR = 2.23; 1.28-3.90, respectively). Our study demonstrates that abdominal, rather than general, obesity is an indisputable risk factor for EAC and also provides evidence for a protective effect of gluteofemoral (subcutaneous) adipose tissue in EAC. Our study further shows that general obesity is not a risk factor for GCC and GNCC, while the role of abdominal obesity in GCC needs further investigation.

  11. Adiponectin profile and Irisin expression in Italian obese children: Association with insulin-resistance.

    PubMed

    Nigro, Ersilia; Scudiero, Olga; Ludovica Monaco, Maria; Polito, Rita; Schettino, Pietro; Grandone, Anna; Perrone, Laura; Miraglia Del Giudice, Emanuele; Daniele, Aurora

    2017-04-03

    Adiponectin (Acrp30), its high molecular weight (HMW) oligomers, and Irisin are molecules involved in several metabolic processes. To investigate if these cytokines could represent new metabolic markers, we evaluated the expression of Acrp30 and Irisin in serum of obese children from South Italy affected by different degrees of insulin resistance (IR). The anthropometric and metabolic features were evaluated in 27 obese children versus 13 age-matched controls. The expression of Acrp30, its pattern and Irisin were investigated by ELISA, western blotting and fast protein liquid chromatography. The HOMA index was significantly higher in obese children versus controls, and metabolic syndrome was more prevalent in obese children with elevated IR versus those with normal HOMA (38% vs 16%). Total Acrp30 and HMW oligomers were significantly lower in obese than in control children, and the difference was more pronounced in children with HOMA >3.4. In control and obese children, total Acrp30 and HMW oligomers were inversely related to HOMA (r-0.38, p 0.02; r-0.35, p 0.03). Irisin was significantly higher in obese than in control children, and was inversely correlated with Acrp30 and HMW (r-0.32, p 0.04; r-0.39, p 0.01). The inverse correlation of Acpr30 and HMW oligomers with HOMA indicates that Acpr30 is directly involved in IR status. Moreover, the inverse correlation between Irisin and Acrp30 and, more significantly, between Irisin and HMW oligomers suggests that the two cytokines are closely connected. The use of Acrp30, HMW oligomers and Irisin as predictive factors of IR in obese children remains to be further elucidated.

  12. Long-term ingestion of monosodium L-glutamate did not induce obesity, dyslipidemia or insulin resistance: a two-generation study in mice.

    PubMed

    Nakamura, Hidehiro; Kawamata, Yasuko; Kuwahara, Tomomi; Smriga, Miro; Sakai, Ryosei

    2013-01-01

    The use of monosodium glutamate (MSG) as a flavor enhancer spans more than 100 y and there are many studies indicating the safety of general use of MSG. Recently, however, Collison et al. (2010) reported a two-generation study with a low dose of MSG that caused abdominal obesity, insulin resistance and dyslipidemia in mice. Due to public health concerns over metabolic syndrome, their report merits careful analysis. The present study attempted to repeat the Collison et al. findings. Groups of male or female C57BL/6J mice were fed a control diet or one supplemented with high-fructose corn syrup (HFCS) at a level of 20%. Drinking water control was provided or treatment groups were given 0.064% MSG solution (w/v). Diets and MSG administration continued throughout mating and during gestation and lactation periods. To further investigate the effects of ingestion of MSG, the offspring were continued on the same dosing conditions until they reached 32 wk of age. MSG administration in mice fed a normal or a HFCS diet throughout gestation and for 32 wk after birth, did not affect growth, girth size, abdominal fat weight or body composition. This study reports that MSG did not trigger insulin resistance, dyslipidemia or hepatic steatosis, regardless of the diet, not reproducing the results of the above-mentioned study (Collison et al., 2010).

  13. Blueberry intake alters skeletal muscle and adipose tissue peroxisome proliferator-activated receptor activity and reduces insulin resistance in obese rats.

    PubMed

    Seymour, E Mitchell; Tanone, Ignasia I; Urcuyo-Llanes, Daniel E; Lewis, Sarah K; Kirakosyan, Ara; Kondoleon, Michael G; Kaufman, Peter B; Bolling, Steven F

    2011-12-01

    Metabolic syndrome can precede the development of type 2 diabetes and cardiovascular disease and includes phenotypes such as obesity, systemic inflammation, insulin resistance, and hyperlipidemia. A recent epidemiological study indicated that blueberry intake reduced cardiovascular mortality in humans, but the possible genetic mechanisms of this effect are unknown. Blueberries are a rich source of anthocyanins, and anthocyanins can alter the activity of peroxisome proliferator-activated receptors (PPARs), which affect energy substrate metabolism. The effect of blueberry intake was assessed in obesity-prone rats. Zucker Fatty and Zucker Lean rats were fed a higher-fat diet (45% of kcal) or a lower-fat diet (10% of kcal) containing 2% (wt/wt) freeze-dried whole highbush blueberry powder or added sugars to match macronutrient and calorie content. In Zucker Fatty rats fed a high-fat diet, the addition of blueberry reduced triglycerides, fasting insulin, homeostasis model index of insulin resistance, and glucose area under the curve. Blueberry intake also reduced abdominal fat mass, increased adipose and skeletal muscle PPAR activity, and affected PPAR transcripts involved in fat oxidation and glucose uptake/oxidation. In Zucker Fatty rats fed a low-fat diet, the addition of blueberry also significantly reduced liver weight, body weight, and total fat mass. Finally, Zucker Lean rats fed blueberry had higher body weight and reduced triglycerides, but all other measures were unaffected. In conclusion, whole blueberry intake reduced phenotypes of metabolic syndrome in obesity-prone rats and affected PPAR gene transcripts in adipose and muscle tissue involved in fat and glucose metabolism.

  14. Emerging evidence for beneficial macrophage functions in atherosclerosis and obesity-induced insulin resistance.

    PubMed

    Fitzgibbons, Timothy P; Czech, Michael P

    2016-03-01

    The discovery that obesity promotes macrophage accumulation in visceral fat led to the emergence of a new field of inquiry termed "immunometabolism". This broad field of study was founded on the premise that inflammation and the corresponding increase in macrophage number and activity was a pathologic feature of metabolic diseases. There is abundant data in both animal and human studies that supports this assertation. Established adverse effects of inflammation in visceral fat include decreased glucose and fatty acid uptake, inhibition of insulin signaling, and ectopic triglyceride accumulation. Likewise, in the atherosclerotic plaque, macrophage accumulation and activation results in plaque expansion and destabilization. Despite these facts, there is an accumulating body of evidence that macrophages also have beneficial functions in both atherosclerosis and visceral obesity. Potentially beneficial functions that are common to these different contexts include the regulation of efferocytosis, lipid buffering, and anti-inflammatory effects. Autophagy, the process by which cytoplasmic contents are delivered to the lysosome for degradation, is integral to many of these protective biologic functions. The macrophage utilizes autophagy as a molecular tool to maintain tissue integrity and homeostasis at baseline (e.g., bone growth) and in the face of ongoing metabolic insults (e.g., fasting, hypercholesterolemia, obesity). Herein, we highlight recent evidence demonstrating that abrogation of certain macrophage functions, in particular autophagy, exacerbates both atherosclerosis and obesity-induced insulin resistance. Insulin signaling through mammalian target of rapamycin (mTOR) is a crucial regulatory node that links nutrient availability to macrophage autophagic flux. A more precise understanding of the metabolic substrates and triggers for macrophage autophagy may allow therapeutic manipulation of this pathway. These observations underscore the complexity of the field

  15. Obesity, insulin resistance and incident small vessel disease on MRI: the Atherosclerosis Risk in Communities Study

    PubMed Central

    Dearborn, Jennifer L.; Schneider, Andrea L. C.; Sharrett, A. Richey; Mosley, Thomas H.; Bezerra, Daniel C; Knopman, David S.; Selvin, Elizabeth; Jack, Clifford R.; Coker, Laura H.; Alonso, Alvaro; Wagenknecht, Lynne E.; Windham, Beverly G.; Gottesman, Rebecca F.

    2015-01-01

    Background and purpose The term “metabolic syndrome” (MetS) describes the clustering of risk factors found in many individuals with obesity. Due to their pathophysiology, we hypothesized that two features of MetS, central obesity and insulin resistance (IR), would be associated with cerebrovascular changes on MRI, and specifically with incident lacunar disease and not white matter hyperintensity progression (WMH). Methods Risk factors were defined at study baseline in 934 participants in the Atherosclerosis Risk in Communities (ARIC) study who completed two brain MRIs approximately ten years apart. WMH progression and incident lacunes between the two MRIs were determined. An IR score for each participant was created using principal component analysis of 11 risk factors, including (among others): insulin, HOMA-IR, body mass index (BMI) and waist circumference. MetS (presence/absence), using standard clinical definitions, and IR score at the first MRI, were independent variables, evaluated in multivariate logistic regression to determine odds of WMH progression (Q5 vs. Q1–4) and incident lacunes. Results MetS (adjusted OR 1.98; 95% confidence interval (CI) 1.28, 3.05) and IR score (adjusted OR per 1-standard deviation increase: 1.33, 95% CI 1.05, 1.68) were associated with incident lacunes but not with WMH progression. Insulin, HOMA-IR and BMI were not associated with incident lacunes or WMH progression in separate models. Conclusions The IR score and central obesity are associated with incident lacunar disease but not WMH progression in individuals. Central obesity and IR may be important risk factors to target to prevent lacunar disease. PMID:26451022

  16. Smad3 deficiency protects mice from obesity-induced podocyte injury that precedes insulin resistance.

    PubMed

    Sun, Yu B Y; Qu, Xinli; Howard, Victor; Dai, Lie; Jiang, Xiaoyun; Ren, Yi; Fu, Ping; Puelles, Victor G; Nikolic-Paterson, David J; Caruana, Georgina; Bertram, John F; Sleeman, Mark W; Li, Jinhua

    2015-08-01

    Signaling by TGF-β/Smad3 plays a key role in renal fibrosis. As obesity is one of the major risk factors of chronic and end-stage renal disease, we studied the role of Smad3 signaling in the pathogenesis of obesity-related renal disease. After switching to a high fat diet, the onset of Smad3 C-terminal phosphorylation, increase in albuminuria, and the early stages of peripheral and renal insulin resistance occurred at 1 day, and 4 and 8 weeks, respectively, in C57BL/6 mice. The loss of synaptopodin, a functional marker of podocytes, and phosphorylation of the Smad3 linker region (T179 and S213) appeared after 4 weeks of the high fat diet. This suggests a temporal pattern of Smad3 signaling activation leading to kidney injury and subsequent insulin resistance in the development of obesity-related renal disease. In vivo, Smad3 knockout attenuated the high fat diet-induced proteinuria, renal fibrosis, overall podocyte injury, and mitochondrial dysfunction in podocytes. In vitro palmitate caused a rapid activation of Smad3 in 30 min, loss of synaptopodin in 2 days, and impaired insulin signaling in 3 days in isolated mouse podocytes. Blockade of either Smad3 phosphorylation by SIS3 (a Smad3 inhibitor) or T179 phosphorylation by flavopiridol (a CDK9 inhibitor) prevented the palmitate-induced loss of synaptopodin and mitochondrial function in podocytes. Thus, Smad3 signaling plays essential roles in obesity-related renal disease and may be a novel therapeutic target.

  17. Concentrations of chromium, selenium, and copper in the hair of viscerally obese adults are associated with insulin resistance.

    PubMed

    Kim, Ha-Na; Song, Sang-Wook

    2014-05-01

    Visceral adiposity is linked to the development of insulin resistance, which is a condition that may contribute to metabolic abnormalities and cardiovascular disease. Various minerals play essential roles in different metabolic functions in the body. Thus, the relationships between mineral concentrations in the hair and insulin resistance were analyzed in 144 Korean adults (71 viscerally obese subjects and 73 normal control subjects) in this cross-sectional study. Visceral obesity was measured using a bioelectrical impedance analysis (BIA), and insulin resistance levels were assessed using the homeostasis model assessment insulin resistance (HOMA-IR) index. The viscerally obese group exhibited significantly higher levels of serum glucose (96.5 vs 91.0 mg/dL, P = 0.023), insulin concentration (4.78 vs 2.98 μIU/mL, P = 0.003), and the HOMA-IR index (1.18 vs 0.64, P = 0.003) compared with the normal control group. After adjusting for age and sex, there was a positive correlation between copper levels in the hair and the HOMA-IR index in the viscerally obese group (r = 0.241, P = 0.046) whereas chromium and selenium levels in the hair were negatively correlated with the HOMA-IR index (r = -0.256, P = 0.034, and r = -0.251, P = 0.038, respectively). Thus, chromium and selenium levels in the hair of viscerally obese adults were inversely associated with insulin resistance, whereas copper levels in the hair were positively associated with insulin resistance. This suggests that the mineral status of viscerally obese adults might play a role in the development of insulin resistance.

  18. Deficiency of the leukotriene B4 receptor, BLT-1, protects against systemic insulin resistance in diet-induced obesity.

    PubMed

    Spite, Matthew; Hellmann, Jason; Tang, Yunan; Mathis, Steven P; Kosuri, Madhavi; Bhatnagar, Aruni; Jala, Venkatakrishna R; Haribabu, Bodduluri

    2011-08-15

    Chronic inflammation is an underlying factor linking obesity with insulin resistance. Diet-induced obesity promotes an increase in circulating levels of inflammatory monocytes and their infiltration into expanding adipose tissue. Nevertheless, the endogenous pathways that trigger and sustain chronic low-grade inflammation in obesity are incompletely understood. In this study, we report that a high-fat diet selectively increases the circulating levels of CD11b(+) monocytes in wild-type mice that express leukotriene B(4) receptor, BLT-1, and that this increase is abolished in BLT-1-null mice. The accumulation of classically activated (M1) adipose tissue macrophages (ATMs) and the expression of proinflammatory cytokines and chemokines (i.e., IL-6 and Ccl2) was largely blunted in adipose tissue of obese BLT-1(-/-) mice, whereas the ratio of alternatively activated (M2) ATMs to M1 ATMs was increased. Obese BLT-1(-/-) mice were protected from systemic glucose and insulin intolerance and this was associated with a decrease in inflammation in adipose tissue and liver and a decrease in hepatic triglyceride accumulation. Deletion of BLT-1 prevented high fat-induced loss of insulin signaling in liver and skeletal muscle. These observations elucidate a novel role of chemoattractant receptor, BLT-1, in promoting monocyte trafficking to adipose tissue and promoting chronic inflammation in obesity and could lead to the identification of new therapeutic targets for treating insulin resistance in obesity.

  19. Arterial insulin resistance in Yucatan micropigs with diet-induced obesity and metabolic syndrome

    PubMed Central

    Low Wang, Cecilia C.; Lu, Li; Leitner, J. Wayne; Sarraf, Mohammad; Gianani, Roberto; Draznin, Boris; Greyson, Clifford R.; Reusch, Jane E. B.; Schwartz, Gregory G.

    2013-01-01

    Aim Metabolic syndrome affects a large proportion of the population and increases cardiovascular disease risk. Because metabolic syndrome often co-exists clinically with atherosclerosis, it is difficult to distinguish their respective contributions to vascular abnormalities. Accordingly, we utilized a porcine dietary model of metabolic syndrome without atherosclerosis to investigate early abnormalities of vascular function and signaling. Methods Thirty-two Yucatan micropigs were fed either a high fat, high simple sugar, high calorie (HFHS) or standard chow diet (STD) for 6 months. Neither diet contained added cholesterol. Blood pressure and flow-mediated vasodilatation were assessed at baseline and 6 months. Aortas were harvested at 6 months to assess histology, insulin signaling, and endothelial nitric oxide (eNOS) phosphorylation. Results HFHS pigs developed characteristic of metabolic syndrome including obesity, dyslipidemia, and insulin resistance, but without histological evidence of atherosclerosis. Although arterial intima-media thickness did not differ between groups, vascular dysfunction in HFHS was manifest by increased blood pressure and impaired flow-mediated vasodilation of the femoral artery. Compared with STD, aortas from HFHS exhibited increased p85α expression and Ser307 IRS-1 phosphorylation, and blunted insulin-stimulated IRS-1-associated phosphatidylinositol (PI) 3-kinase activity. In the absence of insulin stimulation, aortic Akt Ser473-phosphorylation was greater in HFHS than in STD. With insulin stimulation, Akt phosphorylation increased in STD, but not HFHS. Insulin-induced Ser1177-phosphorylation of eNOS was decreased in HFHS, compared with STD. Conclusions Pigs with metabolic syndrome develop early vascular dysfunction and aortic insulin signaling abnormalities, and could be a useful model for early human vascular abnormalities in this condition. PMID:23558108

  20. Insulin response in individual tissues of control and gold thioglucose-obese mice in vivo with (1-/sup 14/C)2-deoxyglucose

    SciTech Connect

    Cooney, G.J.; Astbury, L.D.; Williams, P.F.; Caterson, I.D.

    1987-02-01

    The dose-response characteristics of several glucose-utilizing tissues (brain, heart, white adipose tissue, brown adipose tissue, and quadriceps muscle) to a single injection of insulin have been compared in control mice and mice made obese with a single injection of gold thioglucose (GTG). Tissue content of (1-/sup 14/C)2-deoxyglucose 6-phosphate and blood disappearance rate of (1-/sup 14/C)2-deoxyglucose (2-DG) were measured at nine different insulin doses and used to calculate rates of 2-DG uptake and phosphorylation in tissues from control and obese mice. The insulin sensitivity of tissues reflected in the ED50 of insulin response varied widely, and brown adipose tissue was the most insulin-sensitive tissue studied. In GTG-obese mice, heart, quadriceps, and brown adipose tissue were insulin resistant (demonstrated by increased ED50), whereas in white adipose tissue, 2-DG phosphorylation was more sensitive to insulin. Brain 2-DG phosphorylation was insulin independent in control and obese animals. The largest decrease in insulin sensitivity in GTG-obese mice was observed in brown adipose tissue. The loss of diet-induced thermogenesis in brown adipose tissue as a result of the hypothalamic lesion in GTG-obese mice could be a major cause of insulin resistance in brown adipose tissue. Because brown adipose tissue can make a major contribution to whole-body glucose utilization, insulin resistance in this tissue may have a significant effect on whole-animal glucose homeostasis in GTG-obese mice.

  1. Effect of Plasma Uric Acid on Antioxidant Capacity, Oxidative Stress, and Insulin Sensitivity in Obese Subjects

    PubMed Central

    Fabbrini, Elisa; Serafini, Mauro; Colic Baric, Irena; Hazen, Stanley L.; Klein, Samuel

    2014-01-01

    Oxidative stress is purported to be involved in the pathogenesis of obesity-associated insulin resistance. We evaluated whether alterations in levels of circulating uric acid (UA), a systemic antioxidant, affects the following: 1) systemic (plasma and saliva) nonenzymatic antioxidant capacity (NEAC); 2) markers of systemic (urinary 8-iso-prostaglandin-F2α) and muscle (carbonylated protein content) oxidative stress; and 3) whole-body insulin sensitivity (percentage increase in glucose uptake during a hyperinsulinemic-euglycemic clamp procedure). Thirty-one obese subjects (BMI 37.1 ± 0.7 kg/m2) with either high serum UA (HUA; 7.1 ± 0.4 mg/dL; n = 15) or normal serum UA (NUA; 4.5 ± 0.2 mg/dL; n = 16) levels were studied; 13 subjects with HUA levels were studied again after reduction of serum UA levels to 0 by infusing a recombinant urate oxidase. HUA subjects had 20–90% greater NEAC, but lower insulin sensitivity (40%) and levels of markers of oxidative stress (30%) than subjects in the NUA group (all P < 0.05). Acute UA reduction caused a 45–95% decrease in NEAC and a 25–40% increase in levels of systemic and muscle markers of oxidative stress (all P < 0.05), but did not affect insulin sensitivity (from 168 ± 25% to 156 ± 17%, P = NS). These results demonstrate that circulating UA is a major antioxidant and might help protect against free-radical oxidative damage. However, oxidative stress is not a major determinant of insulin action in vivo. PMID:24353177

  2. Serum Resistin Levels Are Associated with Adiposity and Insulin Sensitivity in Obese Hispanic Subjects

    PubMed Central

    Nieva-Vazquez, Adriana; Torres-Rasgado, Enrique; López-López, José G.; Romero, Jose R.

    2014-01-01

    Abstract Background and Aims: Resistin is involved in the development of obesity and insulin resistance (IR) in mice and may play a similar role in humans through mechanisms that remain unresolved. The objective of this study was to characterize the relationship between resistin levels in obese subjects with and without IR among Hispanic subjects. Material and Methods: A cross-sectional study was performed on 117 nondiabetic Hispanic subjects of both genders that were allocated into three study groups: A control group (n=47) of otherwise healthy individuals in metabolic balance, a group with obesity (OB) (n=36), and a group with obesity and IR (OB-IR) (n=34). Anthropometric and clinical characterization was carried out, and resistin levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: We found that resistin levels were higher in OB and OB-IR groups when compared to the control group (1331.79±142.15 pg/mL, 1266.28±165.97 pg/mL vs. 959.21±171.43 pg/mL; P<0.05), an effect that was not confounded by age (control, 34.04±10.00 years; OB, 37.30±10.78 years; and OB-IR, 35.67±10.15 years). In addition, we observed a significant correlation (P<0.001) between resistin levels and higher adiposity and insulin sensitivity (IS) in our cohort. Conclusions: Our results suggest that higher resistin levels are associated with higher adiposity and lower IS among obese Hispanic subjects. PMID:24266722

  3. Early cardiovascular changes occurring in diet-induced, obese insulin-resistant rats.

    PubMed

    Huisamen, Barbara; Dietrich, Daneel; Bezuidenhout, Nicole; Lopes, John; Flepisi, Brian; Blackhurst, Dee; Lochner, Amanda

    2012-09-01

    The metabolic syndrome is recognized as a cluster of disturbances associated with obesity, type 2 diabetes and hypertension. Over the past two decades, the number of people with the metabolic syndrome has increased at an alarming rate. This increase is associated with the global epidemic of both obesity and diabetes. Cardiovascular mortality is increased among diabetics and obesity-related insulin-resistant patients, and obesity is currently recognized as independent risk factor for cardiovascular disease. We aimed to establish the effects of a short period of an altered diet on the heart using a rat model of hyperphagia-induced obesity (diet supplemented with sucrose and condensed milk for 8 weeks = DIO) compared to age-matched controls. Isolated, perfused hearts were subjected to global or regional ischaemia/reperfusion. Function on reperfusion was recorded and infarct size determined. A plasma lipid profile was established via HPLC-based methods and proteins involved in metabolic signalling determined either by western blotting or RT-PCR. 8 weeks of diet resulted in whole-body but not myocardial insulin resistance, increased plasma triglyceride and phospholipid levels as well as increased lipid peroxidation. Despite the similar baseline function, hearts from DIO animals showed significantly poorer postischaemic recovery than controls (41.9 % RPP recovery vs 57.9 %, P < 0.05, n = 7-11/group) but surprisingly, smaller infarct size (24.95 ± 1.97 vs 47.26 ± 4.05 % of the area at risk, P < 0.005, n = 8/group). Basal phosphorylation of PKB/Akt was elevated but IRS-1 and SERCA-2 expression severely downregulated. In conclusion, after only 8 weeks of a slight change in diet, the rat heart shows signs of metabolic remodelling. Some of these changes may be protective but others may be detrimental and eventually lead to maladaptation.

  4. Effect of zinc supplementation on serum leptin levels and insulin resistance of obese women.

    PubMed

    Marreiro, Dilina do Nascimento; Geloneze, Bruno; Tambascia, Marcos A; Lerário, Antonio C; Halpern, Alfredo; Cozzolino, Silvia Maria Franciscato

    2006-08-01

    Leptin is thought to be a lipostatic signal that contributes to body weight regulation. Zinc might play an important role in appetite regulation and its administration stimulates leptin production. However, there are few reports in the literature on its role on leptin levels in the obese population. The present work assesses the effect of zinc supplementation on serum leptin levels in insulin resistance (IR). A prospective double-blind, randomized, clinical, placebo-controlled study was conducted. Fifty-six normal glucose-tolerant obese women (age: 25-45 yr, body mass index [BMI] = 36.2 +/- 2.3 kg/m2) were randomized for treatment with 30 mg zinc daily for 4 wk. Baseline values of both groups were similar for age, BMI, caloric intake, insulin concentration, insulin resistance, and zinc concentration in diet, plasma, urine, and erythrocytes. Insulin and leptin were measured by radioimmunoassay and IR was estimated by the homeostasis model assessment (HOMA). The determinations of zinc in plasma, erythrocytes, and 24- h urine were performed by using atomic absorption spectrophotometry. After 4 wk, BMI, fasting glucose, and zinc concentration in plasma and erythrocyte did not change in either group, although zinc concentration in the urine increased from 385.9 +/- 259.3 to 470.2 +/- 241.2 +/- microg/24 h in the group with zinc supplementation (p < 0.05). Insulin did not change in the placebo group, whereas there was a significant decrease of this hormone in the supplemented group. HOMA also decreased from 5.8 +/- 2.6 to 4.3 +/- 1.7 (p < 0.05) in the zinc-supplemented group but did not change in the placebo group. Leptin did not change in the placebo group. In the zinc group, leptin was 23.6 +/- 12.3 microg/L and did not change. More human data from a unique population of obese individuals with documented insulin resistance would be useful in guiding future studies on zinc supplementation (with higher doses or longer intervals) or different measures.

  5. Anhydroicaritin improves diet-induced obesity and hyperlipidemia and alleviates insulin resistance by suppressing SREBPs activation.

    PubMed

    Zheng, Zu-Guo; Zhou, Ya-Ping; Zhang, Xin; Thu, Pyone Myat; Xie, Zhi-Shen; Lu, Chong; Pang, Tao; Xue, Bin; Xu, Da-Qian; Chen, Yan; Chen, Xiao-Wei; Li, Hui-Jun; Xu, Xiaojun

    2016-12-15

    SREBPs play important roles in the regulation of lipid metabolism, and are closely related to the occurrence and development of many metabolic diseases. Small molecular inhibitors of SERBPs are important tools in developing efficient treatment of metabolic diseases. However, there are no listing drug targeting SREBPs. Therefore, there is an urgent need to develop highly specific small molecules that inhibit SREBPs. In this study, using a hepatocyte-based high-throughput screening, we identified anhydroicaritin (AHI) as a novel inhibitor of SREBPs. HepG2, HL-7702, and human primary hepatocytes were used to verify the effects of AHI. We explored the mechanism by which AHI blocks the binding of SCAP/SREBPs complex with Sec23α/24D via regulating LKB1/AMPK/mTOR pathway. AHI reduced liver cell lipid level by preventing de novo lipogenesis. In diet induced obese mice, AHI ameliorated obesity, insulin resistance, fatty accumulation in liver and hyperlipemia. In conclusion, AHI improves diet-induced obesity and alleviates insulin resistance by suppressing SREBPs maturation which is dependent on LKB1/AMPK/mTOR pathway. Thus, AHI can serve as a leading compound for pharmacological control of metabolic diseases.

  6. Insulin-induced generation of reactive oxygen species and uncoupling of nitric oxide synthase underlie the cerebrovascular insulin resistance in obese rats.

    PubMed

    Katakam, Prasad V G; Snipes, James A; Steed, Mesia M; Busija, David W

    2012-05-01

    Hyperinsulinemia accompanying insulin resistance (IR) is an independent risk factor for stroke. The objective is to examine the cerebrovascular actions of insulin in Zucker obese (ZO) rats with IR and Zucker lean (ZL) control rats. Diameter measurements of cerebral arteries showed diminished insulin-induced vasodilation in ZO compared with ZL. Endothelial denudation revealed vasoconstriction to insulin that was greater in ZO compared with ZL. Nonspecific inhibition of nitric oxide synthase (NOS) paradoxically improved vasodilation in ZO. Scavenging of reactive oxygen species (ROS), supplementation of tetrahydrobiopterin (BH(4)) precursor, and inhibition of neuronal NOS or NADPH oxidase or cyclooxygenase (COX) improved insulin-induced vasodilation in ZO. Immunoblot experiments revealed that insulin-induced phosphorylation of Akt, endothelial NOS, and expression of GTP cyclohydrolase-I (GTP-CH) were diminished, but phosphorylation of PKC and ERK was enhanced in ZO arteries. Fluorescence studies showed increased ROS in ZO arteries in response to insulin that was sensitive to NOS inhibition and BH(4) supplementation. Thus, a vicious cycle of abnormal insulin-induced ROS generation instigating NOS uncoupling leading to further ROS production underlies the cerebrovascular IR in ZO rats. In addition, decreased bioavailability and impaired synthesis of BH(4) by GTP-CH induced by insulin promoted NOS uncoupling.

  7. Inhibition of 72 kDa inositol polyphosphate 5-phosphatase E improves insulin signal transduction in diet-induced obesity.

    PubMed

    Bertelli, Daniela F; Coope, Andressa; Caricilli, Andrea M; Prada, Patricia O; Saad, Mario J; Velloso, Licio A; Araujo, Eliana P

    2013-05-01

    The 72 kDa inositol polyphosphate 5-phosphatase E (72k-5ptase) controls signal transduction through the catalytic dephosphorylation of the 5-position of membrane-bound phosphoinositides. The reduction of 72k-5ptase expression in the hypothalamus results in improved hypothalamic insulin signal transduction and reduction of food intake and body mass. Here, we evaluated the tissue distribution and the impact of obesity on the expression of 72k-5ptase in peripheral tissues of experimental animals. In addition, insulin signal transduction and action were determined in an animal model of obesity and insulin resistance treated with an antisense (AS) oligonucleotide that reduces 72k-5ptase expression. In lean Wistar rats, 72k-5ptase mRNA and protein are found in highest levels in heart, skeletal muscle, and white adipose tissue. In three distinct models of obesity, Wistar rats, Swiss mice fed on high-fat diet, and leptin-deficient ob/ob mice, the expression of 72k-5ptase is increased in skeletal muscle and adipose tissue. The treatment of obese Wistar rats with an anti-72k-5ptase AS oligonucleotide results in significant reduction of 72k-5ptase catalytic activity, which is accompanied by reduced food intake and body mass and improved insulin signal transduction and action as determined by immunoblotting and clamp studies respectively. 72k-5ptase expression is increased in obesity and its AS inhibition resulted in a significant improvement in insulin signal transduction and restoration of glucose homeostasis.

  8. Transient receptor potential vanilloid type-1 channel regulates diet-induced obesity, insulin resistance, and leptin resistance.

    PubMed

    Lee, Eunjung; Jung, Dae Young; Kim, Jong Hun; Patel, Payal R; Hu, Xiaodi; Lee, Yongjin; Azuma, Yoshihiro; Wang, Hsun-Fan; Tsitsilianos, Nicholas; Shafiq, Umber; Kwon, Jung Yeon; Lee, Hyong Joo; Lee, Ki Won; Kim, Jason K

    2015-08-01

    Insulin resistance is a major characteristic of obesity and type 2 diabetes, but the underlying mechanism is unclear. Recent studies have shown a metabolic role of capsaicin that may be mediated via the transient receptor potential vanilloid type-1 (TRPV1) channel. In this study, TRPV1 knockout (KO) and wild-type (WT) mice (as controls) were fed a high-fat diet (HFD), and metabolic studies were performed to measure insulin and leptin action. The TRPV1 KO mice became more obese than the WT mice after HFD, partly attributed to altered energy balance and leptin resistance in the KO mice. The hyperinsulinemic-euglycemic clamp experiment showed that the TRPV1 KO mice were more insulin resistant after HFD because of the ∼40% reduction in glucose metabolism in the white and brown adipose tissue, compared with that in the WT mice. Leptin treatment failed to suppress food intake, and leptin-mediated hypothalamic signal transducer and activator of transcription (STAT)-3 activity was blunted in the TRPV1 KO mice. We also found that the TRPV1 KO mice were more obese and insulin resistant than the WT mice at 9 mo of age. Taken together, these results indicate that lacking TRPV1 exacerbates the obesity and insulin resistance associated with an HFD and aging, and our findings further suggest that TRPV1 has a major role in regulating glucose metabolism and hypothalamic leptin's effects in obesity.

  9. In vivo nitric oxide suppression of lipolysis in subcutaneous abdominal adipose tissue is greater in obese than lean women.

    PubMed

    Hickner, Robert C; Kemeny, Gabor; Clark, Paige D; Galvin, Vaughna B; McIver, Kerry L; Evans, Chris A; Carper, Michael J; Garry, Joseph P

    2012-06-01

    Mounting evidence suggests there is a reduced mobilization of stored fat in obese compared to lean women. It has been suggested that this decreased lipid mobilization may lead to, or perpetuate, the obese state; however, there may be a beneficial effect of reduced lipolysis, either by allowing for a sink of excess fatty acids, or by limiting a potentially harmful rise in interstitial and circulating fatty acid concentration. Nitric oxide (NO) may be responsible for a portion of the reduced in vivo rates of lipolysis in obese women because NO reduces adipose tissue lipolysis and adipose tissue nitric oxide synthase (NOS) mRNA is higher in obese than lean individuals. The purpose of this study was to determine if the inhibition of NOS by L-N(g)-monomethyl-L-arginine (L-NMMA) in the absence and presence of lipolytic stimulation would result in a larger increase in lipolytic rate in obese (OB) than lean (LN) women. Microdialysis probes were inserted into the subcutaneous abdominal adipose tissue of seven obese and six lean women to monitor lipolysis. Dialysate glycerol concentration increased in response to L-NMMA in OB (basal 125 ± 26 µmol/l; L-NMMA 225 ± 35 µmol/l) to a greater extent than in LN (basal 70 ± 18 µmol/l; L-NMMA 84 ± 20 µmol/l) women (P < 0.05). Dialysate glycerol increased to a similar extent in OB and LN in response to adrenergic stimulation by isoprenaline or norepinephrine in the presence of L-NMMA. The differential glycerol responses to L-NMMA between obese and lean could not be explained by differential blood flow responses. It can be concluded that NO suppresses basal lipolysis in obese women to a greater extent than in lean women.

  10. Detrimental Effects of Diet-Induced Obesity on τ Pathology Are Independent of Insulin Resistance in τ Transgenic Mice

    PubMed Central

    Leboucher, Antoine; Laurent, Cyril; Fernandez-Gomez, Francisco-José; Burnouf, Sylvie; Troquier, Laetitia; Eddarkaoui, Sabiha; Demeyer, Dominique; Caillierez, Raphaëlle; Zommer, Nadège; Vallez, Emmanuelle; Bantubungi, Kadiombo; Breton, Christophe; Pigny, Pascal; Buée-Scherrer, Valérie; Staels, Bart; Hamdane, Malika; Tailleux, Anne; Buée, Luc; Blum, David

    2013-01-01

    The τ pathology found in Alzheimer disease (AD) is crucial in cognitive decline. Midlife development of obesity, a major risk factor of insulin resistance and type 2 diabetes, increases the risk of dementia and AD later in life. The impact of obesity on AD risk has been suggested to be related to central insulin resistance, secondary to peripheral insulin resistance. The effects of diet-induced obesity (DIO) on τ pathology remain unknown. In this study, we evaluated effects of a high-fat diet, given at an early pathological stage, in the THY-Tau22 transgenic mouse model of progressive AD-like τ pathology. We found that early and progressive obesity potentiated spatial learning deficits as well as hippocampal τ pathology at a later stage. Surprisingly, THY-Tau22 mice did not exhibit peripheral insulin resistance. Further, pathological worsening occurred while hippocampal insulin signaling was upregulated. Together, our data demonstrate that DIO worsens τ phosphorylation and learning abilities in τ transgenic mice independently from peripheral/central insulin resistance. PMID:23250356

  11. Hepatic oxidative stress promotes insulin-STAT-5 signaling and obesity by inactivating protein tyrosine phosphatase N2

    PubMed Central

    Gurzov, Esteban N.; Tran, Melanie; Fernandez-Rojo, Manuel A; Merry, Troy L; Zhang, Xinmei; Xu, Yang; Fukushima, Atsushi; Waters, Michael J; Watt, Matthew J; Andrikopoulos, Sofianos; Neel, Benjamin G; Tiganis, Tony

    2015-01-01

    Hepatic insulin resistance is a key contributor to the pathogenesis of obesity and type 2 diabetes (T2D). Paradoxically the development of insulin resistance in the liver is not universal, but pathway-selective, such that insulin fails to suppress gluconeogenesis but promotes lipogenesis, contributing to the hyperglycemia, steatosis and hypertriglyceridemia that underpin the deteriorating glucose control and microvascular complications in T2D. The molecular basis for the pathway-specific insulin resistance remains unknown. Here we report that oxidative stress accompanying obesity inactivates protein-tyrosine phosphatases (PTPs) in the liver, which activates select signaling pathways that exacerbate disease progression. In obese mice, hepatic PTPN2 (TCPTP) inactivation promoted lipogenesis and steatosis and insulin-STAT-5 signaling. The enhanced STAT-5 signaling increased hepatic IGF-1 production, which suppressed central growth hormone release and exacerbated the development of obesity and T2D. Our studies define a mechanism for the development of selective insulin resistance with wide-ranging implications for diseases characterised by oxidative stress. PMID:24954415

  12. Iron and Obesity Status-Associated Insulin Resistance Influence Circulating Fibroblast-Growth Factor-23 Concentrations

    PubMed Central

    Fernández-Real, José Manuel; Puig, Josep; Serrano, Marta; Sabater, Mónica; Rubió, Antoni; Moreno-Navarrete, José María; Fontan, Marina; Casamitjana, Roser; Xifra, Gemma; Ortega, Francisco José; Salvador, Javier; Frühbeck, Gema; Ricart, Wifredo

    2013-01-01

    Fibroblast growth factor 23 (FGF-23) is known to be produced by the bone and linked to metabolic risk. We aimed to explore circulating FGF-23 in association with fatness and insulin sensitivity, atherosclerosis and bone mineral density (BMD). Circulating intact FGF-23 (iFGF-23) and C-terminal (CtFGF-23) concentrations (ELISA) were measured in 133 middle aged men from the general population in association with insulin sensitivity (Cohort 1); and in association with fat mass and bone mineral density (DEXA) and atherosclerosis (intima media thickness, IMT) in 78 subjects (52 women) with a wide range of adiposity (Cohort 2). Circulating iFGF-23 was also measured before and after weight loss. In all subjects as a whole, serum intact and C-terminal concentrations were linearly and positively associated with BMI. In cohort 1, both serum iFGF-23 and CtFGF-23 concentrations increased with insulin resistance. Serum creatinine contributed to iFGF-23 variance, while serum ferritin and insulin sensitivity (but not BMI, age or serum creatinine) contributed to 17% of CtFGF-23 variance. In cohort 2, CtFGF-23 levels were higher in women vs. men, and increased with BMI, fat mass, fasting and post-load serum glucose, insulin, HOMA-IR and PTH, being negatively associated with circulating vitamin D and ferritin levels. The associations of CtFGF-23 with bone density in the radius, lumbar spine and carotid IMT were no longer significant after controlling for BMI. Weight loss led to decreased iFGF-23 concentrations. In summary, the associations of circulating FGF-23 concentration with parameters of glucose metabolism, bone density and atherosclerosis are dependent on iron and obesity status-associated insulin resistance. PMID:23555610

  13. Decreased basal insulin secretion from pancreatic islets of pups in a rat model of maternal obesity.

    PubMed

    Zambrano, Elena; Sosa-Larios, Tonantzin; Calzada, Lizbeth; Ibáñez, Carlos A; Mendoza-Rodríguez, Carmen A; Morales, Angélica; Morimoto, Sumiko

    2016-10-01

    Maternal obesity (MO) is a deleterious condition that enhances susceptibility of adult offspring to metabolic diseases such as type 2 diabetes. The objective is to study the effect of MO on in vitro insulin secretion and pancreatic cellular population in offspring. We hypothesize that a harmful antenatal metabolic environment due to MO diminishes the basal glucose-responsive secretory function of pancreatic beta cells in offspring. Mothers were fed a control (C) or high-fat diet from weaning through pregnancy (120 days) and lactation. At postnatal days (PNDs) 36 and 110, pups were killed, peripheral blood was collected and pancreatic islets were isolated. Basal insulin secretion was measured in vitro in islets for 60 min. It was found that blood insulin, glucose and homeostasis model assessment (HOMA) index were unaffected by maternal diet and age in females. However, male MO offspring at PND 110 showed hyperinsulinemia and insulin resistance compared with C. Body weight was not modified by MO, but fat content was higher in MO pups compared with C pups. Triglycerides and leptin concentrations were higher in MO than in C offspring in all groups except in females at PND 36. Pancreatic islet cytoarchitecture was unaffected by MO. At PND 36, islets of male and female C and MO offspring responded similarly to glucose, but at PND 110, male and female MO offspring islets showed a 50% decrease in insulin secretion. It was concluded that MO impairs basal insulin secretion of offspring with a greater impact on males than females, and this effect mainly manifests in adulthood.

  14. Dehydroepiandrosterone decreases serum tumor necrosis factor-alpha and restores insulin sensitivity: independent effect from secondary weight reduction in genetically obese Zucker fatty rats.

    PubMed

    Kimura, M; Tanaka, S; Yamada, Y; Kiuchi, Y; Yamakawa, T; Sekihara, H

    1998-07-01

    Dehydroepiandrosterone (DHEA) and its sulfate ester are the most abundant circulating adrenal steroids in humans. Administration of DHEA has been reported to have beneficial effects on obesity, hyperlipidemia, diabetes, and atherosclerosis in obese rodents, although its effects on insulin resistance have not been fully elucidated. In this study, the effects of DHEA treatment on insulin sensitivity were investigated in genetically obese Zucker rats, an animal model of insulin resistance, using the euglycemic clamp technique. After 0.4% DHEA was administered for 10 days to female obese Zucker rats aged 16 weeks, body weight and plasma insulin decreased and glucose disposal rate (GDR), which was normally reduced in obese rats, rose significantly compared with age- and sex-matched control obese rats. On the other hand, although the pair-fed obese rats also showed levels of weight reduction similar to those of DHEA-treated rats, the increase in GDR of DHEA-treated rats was significantly greater than in pair-fed rats, suggesting a direct ameliorating effect of DHEA on insulin sensitivity of obese rats. Serum concentration of tumor necrosis factor (TNF)-alpha, one of cytokines causing insulin resistance, was also reduced significantly in DHEA-treated, but not in pair-fed obese rats. In conclusion, our results suggest that DHEA treatment reduces body weight and serum TNF-alpha independently, and that both may ameliorate insulin resistance in obese Zucker fatty rats.

  15. Recombinant Human Growth Hormone and Rosiglitazone for Abdominal Fat Accumulation in HIV-Infected Patients with Insulin Resistance: A Randomized, Double-Blind, Placebo-Controlled, Factorial Trial

    PubMed Central

    Glesby, Marshall J.; Albu, Jeanine; Chiu, Ya-Lin; Ham, Kirsis; Engelson, Ellen; He, Qing; Muthukrishnan, Varalakshmi; Ginsberg, Henry N.; Donovan, Daniel; Ernst, Jerry; Lesser, Martin; Kotler, Donald P.

    2013-01-01

    Background Recombinant human growth hormone (rhGH) reduces visceral adipose tissue (VAT) volume in HIV-infected patients but can worsen glucose homeostasis and lipoatrophy. We aimed to determine if adding rosiglitazone to rhGH would abrogate the adverse effects of rhGH on insulin sensitivity (SI) and subcutaneous adipose tissue (SAT) volume. Methodology/Principal Findings Randomized, double-blind, placebo-controlled, multicenter trial using a 2×2 factorial design in which HIV-infected subjects with abdominal obesity and insulin resistance were randomized to rhGH 3 mg daily, rosiglitazone 4 mg twice daily, combination rhGH + rosiglitazone, or double placebo (control) for 12 weeks. The primary endpoint was change in SI by frequently sampled intravenous glucose tolerance test from entry to week 12. Body composition was assessed by whole body magnetic resonance imaging (MRI) and dual Xray absorptiometry (DEXA). Seventy-seven subjects were randomized of whom 72 initiated study drugs. Change in SI from entry to week 12 differed across the 4 arms by 1-way ANCOVA (P = 0.02); by pair-wise comparisons, only rhGH (decreasing SI; P = 0.03) differed significantly from control. Changes from entry to week 12 in fasting glucose and glucose area under the curve on 2-hour oral glucose tolerance test differed across arms (1-way ANCOVA P = 0.004), increasing in the rhGH arm relative to control. VAT decreased significantly in the rhGH arms (−17.5% in rhGH/rosiglitazone and −22.7% in rhGH) but not in the rosiglitazone alone (−2.5%) or control arms (−1.9%). SAT did not change significantly in any arm. DEXA results were consistent with the MRI data. There was no significant rhGH x rosiglitazone interaction for any body composition parameter. Conclusions/Significance The addition of rosiglitazone abrogated the adverse effects of rhGH on insulin sensitivity and glucose tolerance while not significantly modifying the lowering effect of rhGH on VAT. Trial Registration

  16. Abdominal obesity modifies the risk of hypertriglyceridemia for all-cause and cardiovascular mortality in hemodialysis patients.

    PubMed

    Postorino, Maurizio; Marino, Carmen; Tripepi, Giovanni; Zoccali, Carmine

    2011-04-01

    Hypertriglyceridemia is the most prevalent lipid alteration in end-stage renal disease, and we studied the relationship between serum triglycerides and all-cause and cardiovascular death in these patients. Since abdominal fat modifies the effect of lipids on atherosclerosis, we analyzed the interaction between serum lipids and waist circumference (WC) as a metric of abdominal obesity. In a cohort of 537 hemodialysis patients, 182 died, 113 from cardiovascular causes, over an average follow-up of 29 months. In Cox models that included traditional and nontraditional risk factors, there were significant strong interactions between triglycerides and WC to both all-cause and cardiovascular death. A fixed (50 mg/dl) excess in triglycerides was associated with a progressive lower risk of all-cause and cardiovascular mortality in patients with threshold WC <95 cm but with a progressive increased risk in those above this threshold. A significant interaction between cholesterol and WC with all-cause and cardiovascular death emerged only in models excluding the triglycerides-WC interaction. Neither high-density lipoprotein (HDL) nor non-HDL cholesterol or their interaction terms with WC were associated with study outcomes. Thus, the predictive value of triglycerides and cholesterol for survival and atherosclerotic complications in hemodialysis patients is critically dependent on WC. Hence, intervention studies in end-stage renal disease should specifically target patients with abdominal obesity and hyperlipidemia.

  17. Loss of Hepatic CEACAM1: A Unifying Mechanism Linking Insulin Resistance to Obesity and Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Heinrich, Garrett; Ghadieh, Hilda E.; Ghanem, Simona S.; Muturi, Harrison T.; Rezaei, Khadijeh; Al-Share, Qusai Y.; Bowman, Thomas A.; Zhang, Deqiang; Garofalo, Robert S.; Yin, Lei; Najjar, Sonia M.

    2017-01-01

    The pathogenesis of human non-alcoholic fatty liver disease (NAFLD) remains unclear, in particular in the context of its relationship to insulin resistance and visceral obesity. Work on the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in mice has resolved some of the related questions. CEACAM1 promotes insulin clearance by enhancing the rate of uptake of the insulin-receptor complex. It also mediates a negative acute effect of insulin on fatty acid synthase activity. This positions CEACAM1 to coordinate the regulation of insulin and lipid metabolism. Fed a regular chow diet, global null mutation of Ceacam1 manifest hyperinsulinemia, insulin resistance, obesity, and steatohepatitis. They also develop spontaneous chicken-wire fibrosis, characteristic of non-alcoholic steatohepatitis. Reduction of hepatic CEACAM1 expression plays a significant role in the pathogenesis of diet-induced metabolic abnormalities, as bolstered by the protective effect of hepatic CEACAM1 gain-of-function against the metabolic response to dietary fat. Together, this emphasizes that loss of hepatic CEACAM1 links NAFLD to insulin resistance and obesity. PMID:28184213

  18. Triglyceride to HDL-C Ratio is Associated with Insulin Resistance in Overweight and Obese Children.

    PubMed

    Iwani, Nur Ahmad Kamil Zati; Jalaludin, Muhammad Yazid; Zin, Ruziana Mona Wan Mohd; Fuziah, Md Zain; Hong, Janet Yeow Hua; Abqariyah, Yahya; Mokhtar, Abdul Halim; Wan Nazaimoon, Wan Mohamud

    2017-01-06

    The purpose of this study was to investigate the usefulness of triglyceride to hdl-c ratio (TG:HDL-C) as an insulin resistance (IR) marker for overweight and obese children. A total of 271 blood samples of obese and overweight children aged 9-16 years were analysed for fasting glucose, lipids and insulin. Children were divided into IR and non-insulin resistance, using homeostasis model assessment (HOMA). The children were then stratified by tertiles of TG: HDL-C ratio. The strength between TG:HDL-C ratio and other parameters of IR were quantified using Pearson correlation coefficient (r). Odds ratio was estimated using multiple logistic regression adjusted for age, gender, pubertal stages and IR potential risk factors. Children with IR had significantly higher TG:HDL-C ratio (2.48) (p = 0.01). TG:HDL-C ratio was significantly correlated with HOMA-IR (r = 0.104, p < 0.005) and waist circumference (r = 0.134, p < 0.001). Increasing tertiles of TG:HDL-C ratio showed significant increase in mean insulin level (p = 0.03), HOMA-IR (p = 0.04) and significantly higher number of children with acanthosis nigricans and metabolic syndrome. The odds of having IR was about 2.5 times higher (OR = 2.47; 95% CI 1.23, 4.95; p = 0.01) for those in the highest tertiles of TG:HDL-C ratio. Hence, TG:HDL-C may be a useful tool to identify high risk individuals.

  19. Triglyceride to HDL-C Ratio is Associated with Insulin Resistance in Overweight and Obese Children

    PubMed Central

    Iwani, Nur Ahmad Kamil Zati; Jalaludin, Muhammad Yazid; Zin, Ruziana Mona Wan Mohd; Fuziah, Md Zain; Hong, Janet Yeow Hua; Abqariyah, Yahya; Mokhtar, Abdul Halim; Wan Nazaimoon, Wan Mohamud

    2017-01-01

    The purpose of this study was to investigate the usefulness of triglyceride to hdl-c ratio (TG:HDL-C) as an insulin resistance (IR) marker for overweight and obese children. A total of 271 blood samples of obese and overweight children aged 9–16 years were analysed for fasting glucose, lipids and insulin. Children were divided into IR and non-insulin resistance, using homeostasis model assessment (HOMA). The children were then stratified by tertiles of TG: HDL-C ratio. The strength between TG:HDL-C ratio and other parameters of IR were quantified using Pearson correlation coefficient (r). Odds ratio was estimated using multiple logistic regression adjusted for age, gender, pubertal stages and IR potential risk factors. Children with IR had significantly higher TG:HDL-C ratio (2.48) (p = 0.01). TG:HDL-C ratio was significantly correlated with HOMA-IR (r = 0.104, p < 0.005) and waist circumference (r = 0.134, p < 0.001). Increasing tertiles of TG:HDL-C ratio showed significant increase in mean insulin level (p = 0.03), HOMA-IR (p = 0.04) and significantly higher number of children with acanthosis nigricans and metabolic syndrome. The odds of having IR was about 2.5 times higher (OR = 2.47; 95% CI 1.23, 4.95; p = 0.01) for those in the highest tertiles of TG:HDL-C ratio. Hence, TG:HDL-C may be a useful tool to identify high risk individuals. PMID:28059134

  20. Obesity, type 2 diabetes, and impaired insulin-stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1.

    PubMed

    Reynolds, Leryn J; Credeur, Daniel P; Manrique, Camila; Padilla, Jaume; Fadel, Paul J; Thyfault, John P

    2017-01-01

    Increased endothelin-1 (ET-1) and reduced endothelial nitric oxide phosphorylation (peNOS) are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), but studies examining these links in humans are limited. We sought to assess basal and insulin-stimulated endothelial signaling proteins (ET-1 and peNOS) in skeletal muscle from T2D patients. Ten obese T2D [glucose disposal rate (GDR): 6.6 ± 1.6 mg·kg lean body mass (LBM)(-1)·min(-1)] and 11 lean insulin-sensitive subjects (Lean GDR: 12.9 ± 1.2 mg·kg LBM(-1)·min(-1)) underwent a hyperinsulinemic-euglycemic clamp with vastus lateralis biopsies taken before and 60 min into the clamp. Basal biopsies were also taken in 11 medication-naïve, obese, non-T2D subjects. ET-1, peNOS (Ser1177), and eNOS protein and mRNA were measured from skeletal muscle samples containing native microvessels. Femoral artery blood flow was assessed by duplex Doppler ultrasound. Insulin-stimulated blood flow was reduced in obese T2D (Lean: +50.7 ± 6.5% baseline, T2D: +20.8 ± 5.2% baseline, P < 0.05). peNOS/eNOS content was higher in Lean under basal conditions and, although not increased by insulin, remained higher in Lean during the insulin clamp than in obese T2D (P < 0.05). ET-1 mRNA and peptide were 2.25 ± 0.50- and 1.52 ± 0.11-fold higher in obese T2D compared with Lean at baseline, and ET-1 peptide remained 2.02 ± 1.9-fold elevated in obese T2D after insulin infusion (P < 0.05) but did not increase with insulin in either group (P > 0.05). Obese non-T2D subjects tended to also display elevated basal ET-1 (P = 0.06). In summary, higher basal skeletal muscle expression of ET-1 and reduced peNOS/eNOS may contribute to a reduced insulin-stimulated leg blood flow response in obese T2D patients.

  1. Overweight and General and Abdominal Obesity in a Representative Sample of Spanish Adults: Findings from the ANIBES Study

    PubMed Central

    López-Sobaler, Ana M.; Aparicio, Aránzazu; Aranceta-Bartrina, Javier; Gil, Ángel; González-Gross, Marcela; Serra-Majem, Lluis; Varela-Moreiras, Gregorio; Ortega, Rosa M.

    2016-01-01

    Objective. To analyze the anthropometric parameters from a representative sample of Spanish adults participating in ANIBES study and the prevalence of general and abdominal obesity. Methods. This cross-sectional study focused on 1655 adults aged 18–64 years. Weight, height, and waist circumference (WC) were evaluated, and body mass index (BMI) and waist to height ratio (WHtR) were calculated. A composite index combining BMI and WHtR was designed to establish five groups with different anthropometric status. Results. The prevalence of overweight (OW) was 35.8% and that of obesity was 19.9%. Obesity (OB) was higher among men (OR 1.725, 1.415–2.104; p = 0.000) and each year of age increased the risk of obesity (OR 1.054, 1.045–1.064; p = 0.000). The prevalence of abdominal obesity (WHtR ≥ 0.5) was 58.4%. Only 36.1% of the population had an optimal anthropometric situation (BMI < 25 kg/m2, WHtR < 0.5), whereas 50.1% had weight excess and high WHtR (BMI ≥ 25 kg/m2, WHtR ≥ 0.5). Conclusions. More than half of Spanish population has weight excess and cardiometabolic risk. The results of this study provide an understanding of the current anthropometric situation in the Spanish population, as a first step toward planning interventions and assessing their effectiveness in the future. PMID:27382572

  2. A post-weaning obesogenic diet exacerbates the detrimental effects of maternal obesity on offspring insulin signaling in adipose tissue.

    PubMed

    de Almeida Faria, Juliana; Duque-Guimarães, Daniella; Carpenter, Asha A M; Loche, Elena; Ozanne, Susan E

    2017-03-24

    Previous studies have shown that maternal diet-induced obesity leads to increased risk of type 2 diabetes in offspring. The current study investigated if weaning onto an obesogenic diet exaggerated the detrimental effects of maternal diet-induced obesity in adipose tissue. Maternal obesity and offspring obesity led to reduced expression of key insulin signalling proteins, including insulin receptor substrate-1 (IRS-1). The effects of maternal obesity and offspring obesity were, generally, independent and additive. Irs1 mRNA levels were similar between all four groups of offspring, suggesting that in both cases post-transcriptional regulation was involved. Maternal diet-induced obesity increased miR-126 expression however levels of this miR were not influenced by a post-weaning obesogenic diet. In contrast, a post-weaning obesogenic diet was associated with increased levels of suppressor of cytokine signaling-1, implicating increased degradation of IRS-1 as an underlying mechanism. Our results suggest that whilst programmed reductions in IRS-1 are associated with increased levels of miR-126 and consequently reduced translation of Irs1 mRNA, the effects of a post-weaning obesogenic diet on IRS-1 are mediated by miR-126 independent mechanisms, including increased IRS-1 protein degradation. These divergent mechanisms explain why the combination of maternal obesity and offspring obesity leads to the most pronounced effects on offspring metabolism.

  3. A post-weaning obesogenic diet exacerbates the detrimental effects of maternal obesity on offspring insulin signaling in adipose tissue

    PubMed Central

    de Almeida Faria, Juliana; Duque-Guimarães, Daniella; Carpenter, Asha A. M.; Loche, Elena; Ozanne, Susan E.

    2017-01-01

    Previous studies have shown that maternal diet-induced obesity leads to increased risk of type 2 diabetes in offspring. The current study investigated if weaning onto an obesogenic diet exaggerated the detrimental effects of maternal diet-induced obesity in adipose tissue. Maternal obesity and offspring obesity led to reduced expression of key insulin signalling proteins, including insulin receptor substrate-1 (IRS-1). The effects of maternal obesity and offspring obesity were, generally, independent and additive. Irs1 mRNA levels were similar between all four groups of offspring, suggesting that in both cases post-transcriptional regulation was involved. Maternal diet-induced obesity increased miR-126 expression however levels of this miR were not influenced by a post-weaning obesogenic diet. In contrast, a post-weaning obesogenic diet was associated with increased levels of suppressor of cytokine signaling-1, implicating increased degradation of IRS-1 as an underlying mechanism. Our results suggest that whilst programmed reductions in IRS-1 are associated with increased levels of miR-126 and consequently reduced translation of Irs1 mRNA, the effects of a post-weaning obesogenic diet on IRS-1 are mediated by miR-126 independent mechanisms, including increased IRS-1 protein degradation. These divergent mechanisms explain why the combination of maternal obesity and offspring obesity leads to the most pronounced effects on offspring metabolism. PMID:28338072

  4. The relationship of breakfast skipping and type of breakfast consumed with overweight/obesity, abdominal obesity, other cardiometabolic risk factors and the metabolic syndrome in young adults. NHANES 1999-2006

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The goal of this study was to examine the association between breakfast skipping and type of breakfast consumed with overweight /obesity, abdominal obesity, other cardiometabolic risk factors and the metabolic syndrome. Three breakfast groups were identified (breakfast skippers, ready-to-eat-cereal ...

  5. Modulation of endothelial cell migration by ER stress and insulin resistance: a role during maternal obesity?

    PubMed

    Sáez, Pablo J; Villalobos-Labra, Roberto; Westermeier, Francisco; Sobrevia, Luis; Farías-Jofré, Marcelo

    2014-01-01

    Adverse microenvironmental stimuli can trigger the endoplasmic reticulum (ER) stress pathway, which initiates the unfolded protein response (UPR), to restore protein-folding homeostasis. Several studies show induction of ER stress during obesity. Chronic UPR has been linked to different mechanisms of disease in obese and diabetic individuals, including insulin resistance (IR) and impaired angiogenesis. Endothelial cell (EC) migration is an initial step for angiogenesis, which is associated with remodeling of existing blood vessels. EC migration occurs according to the leader-follower model, involving coordinated processes of chemotaxis, haptotaxis, and mechanotaxis. Thus, a fine-tuning of EC migration is necessary to provide the right timing to form the required vessels during angiogenesis. ER stress modulates EC migration at different levels, usually impairing migration and angiogenesis, although different effects may be observed depending on the tissue and/or microenvironment. In the context of pregnancy, maternal obesity (MO) induces IR in the offspring. Interestingly, several proteins associated with obesity-induced IR are also involved in EC migration, providing a potential link with the ER stress-dependent alterations observed in obese individuals. Different signaling cascades that converge on cytoskeleton regulation directly impact EC migration, including the Akt and/or RhoA pathways. In addition, ER is the main intracellular reservoir for Ca(2+), which plays a pivotal role during EC migration. Therefore, ER stress-related alterations in Ca(2+) signaling or Ca(2+) levels might also produce distorted EC migration. However, the above findings have been studied in the context of adult obesity, and no information has been reported regarding the effect of MO on fetal EC migration. Here we summarize the state of knowledge about the possible mechanisms by which ER stress and IR might impact EC migration and angiogenesis in fetal endothelium exposed to MO during

  6. The Mechanism by Which Safflower Yellow Decreases Body Fat Mass and Improves Insulin Sensitivity in HFD-Induced Obese Mice

    PubMed Central

    Zhu, Huijuan; Wang, Xiangqing; Pan, Hui; Dai, Yufei; Li, Naishi; Wang, Linjie; Yang, Hongbo; Gong, Fengying

    2016-01-01

    Objectives: Safflower yellow (SY) is the main effective ingredient of Carthamus tinctorius L. It has been reported that SY plays an important role in anti-inflammation, anti-platelet aggregation, and inhibiting thrombus formation. In present study, we try to investigate the effects of SY on body weight, body fat mass, insulin sensitivity in high fat diet (HFD)-induced obese mice. Methods: HFD-induced obese male ICR mice were intraperitoneally injected with SY (120 mg kg−1) daily. Eight weeks later, intraperitoneal insulin tolerance test (IPITT), and intraperitoneal glucose tolerance test (IPGTT) were performed, and body weight, body fat mass, serum insulin levels were measured. The expression of glucose and lipid metabolic related genes in white adipose tissue (WAT) were determined by RT-qPCR and western blot technologies. Results: The administration obese mice with SY significantly reduced the body fat mass of HFD-induced obese mice (P < 0.05). IPITT test showed that the insulin sensitivity of SY treated obese mice were evidently improved. The mRNA levels of insulin signaling pathway related genes including insulin receptor substrate 1(IRS1), PKB protein kinase (AKT), glycogen synthase kinase 3β (GSK3β) and forkhead box protein O1(FOXO1) in mesenteric WAT of SY treated mice were significantly increased to 1.9- , 2.8- , 3.3- , and 5.9-folds of that in HFD-induced control obese mice, respectively (P < 0.05). The protein levels of AKT and GSK3β were also significantly increased to 3.0 and 5.2-folds of that in HFD-induced control obese mice, respectively (P < 0.05). Meanwhile, both the mRNA and protein levels of peroxisome proliferator-activated receptorgamma coactivator 1α (PGC1α) in inguinal subcutaneous WAT of SY group were notably increased to 2.5 and 3.0-folds of that in HFD-induced control obese mice (P < 0.05). Conclusions: SY significantly reduce the body fat mass, fasting blood glucose and increase insulin sensitivity of HFD-induced obese mice. The

  7. Using Metabolomic Profiles as Biomarkers for Insulin Resistance in Childhood Obesity: A Systematic Review

    PubMed Central

    Sun, Chenglin

    2016-01-01

    A growing body of evidence has shown the intimate relationship between metabolomic profiles and insulin resistance (IR) in obese adults, while little is known about childhood obesity. In this review, we searched available papers addressing metabolomic profiles and IR in obese children from inception to February 2016 on MEDLINE, Web of Science, the Cochrane Library, ClinicalTrials.gov, and EMASE. HOMA-IR was applied as surrogate markers of IR and related metabolic disorders at both baseline and follow-up. To minimize selection bias, two investigators independently completed this work. After critical selection, 10 studies (including 2,673 participants) were eligible and evaluated by using QUADOMICS for quality assessment. Six of the 10 studies were classified as “high quality.” Then we generated all the metabolites identified in each study and found amino acid metabolism and lipid metabolism were the main affected metabolic pathways in obese children. Among identified metabolites, branched-chain amino acids (BCAAs), aromatic amino acids (AAAs), and acylcarnitines were reported to be associated with IR as biomarkers most frequently. Additionally, BCAAs and tyrosine seemed to be relevant to future metabolic risk in the long-term follow-up cohorts, emphasizing the importance of early diagnosis and prevention strategy. Because of limited scale and design heterogeneity of existing studies, future studies might focus on validating above findings in more large-scale and longitudinal studies with elaborate design. PMID:27517054

  8. Acute effects of different diet compositions on skeletal muscle insulin signalling in obese individuals during caloric restriction

    PubMed Central

    Wang, Cecilia C.L.; Adochio, Rebecca L.; Leitner, J. Wayne; Abeyta, Ian M.; Draznin, Boris; Cornier, Marc-Andre

    2012-01-01

    Objective The cellular effects of restricting fat versus carbohydrate during a low-calorie diet are unclear. The aim of this study was to examine acute effects of energy and macronutrient restriction on skeletal muscle insulin signalling in obesity. Materials/Methods Eighteen obese individuals without diabetes underwent euglycemic-hyperinsulinemic clamp and skeletal muscle biopsy after: (a) 5 days of eucaloric diet (30% fat, 50% carbohydrate), and (b) 5 days of a 30% calorie-restricted diet, either low fat/high carbohydrate (LF/HC: 20% fat, 60% carbohydrate) or high-fat/low carbohydrate (HF/LC: 50% fat, 30% carbohydrate). Results Weight, body composition, and insulin sensitivity were similar between groups after eucaloric diet. Weight loss was similar between groups after hypocaloric diet, 1.3 ± 1.3 kg (p<0.0001 compared with eucaloric). Whole-body insulin sensitivity was unchanged after calorie restriction and similar between groups. However, ex vivo skeletal muscle insulin signalling differed depending on macronutrient composition of calorie-restricted diet. Skeletal muscle of the LF/HC group had increased insulin-stimulated tyrosine phosphorylation of IRS-1, decreased insulin-stimulated Ser 307 phosphorylation of IRS-1, and increased IRS-1-associated phosphatidylinositol (PI)3-kinase activity. Conversely, insulin stimulation of tyrosine phosphorylated IRS-1 was absent and serine 307 phosphorylation of IRS-1 was increased on HF/LC, with blunting of IRS-1-associated PI3-kinase activity. Conclusion Acute caloric restriction with a LF/HC diet alters skeletal muscle insulin signalling in a way that improves insulin sensitivity, while acute caloric restriction with a HF/LC diet induces changes compatible with insulin resistance. In both cases, ex vivo changes in skeletal muscle insulin signalling appear prior to changes in whole body insulin sensitivity. PMID:23174405

  9. Linagliptin improves insulin sensitivity and hepatic steatosis in diet-induced obesity.

    PubMed

    Kern, Matthias; Klöting, Nora; Niessen, Heiko G; Thomas, Leo; Stiller, Detlef; Mark, Michael; Klein, Thomas; Blüher, Matthias

    2012-01-01

    Linagliptin (TRADJENTA™) is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor. DPP-4 inhibition attenuates insulin resistance and improves peripheral glucose utilization in humans. However, the effects of chronic DPP-4 inhibition on insulin sensitivity are not known. The effects of long-term treatment (3-4 weeks) with 3 mg/kg/day or 30 mg/kg/day linagliptin on insulin sensitivity and liver fat content were determined in diet-induced obese C57BL/6 mice. Chow-fed animals served as controls. DPP-4 activity was significantly inhibited (67-89%) by linagliptin (P<0.001). Following an oral glucose tolerance test, blood glucose concentrations (measured as area under the curve) were significantly suppressed after treatment with 3 mg/kg/day (-16.5% to -20.3%; P<0.01) or 30 mg/kg/day (-14.5% to -26.4%; P<0.05) linagliptin (both P<0.01). Liver fat content was significantly reduced by linagliptin in a dose-dependent manner (both doses P<0.001). Diet-induced obese mice treated for 4 weeks with 3 mg/kg/day or 30 mg/kg/day linagliptin had significantly improved glycated hemoglobin compared with vehicle (both P<0.001). Significant dose-dependent improvements in glucose disposal rates were observed during the steady state of the euglycemic-hyperinsulinemic clamp: 27.3 mg/kg/minute and 32.2 mg/kg/minute in the 3 mg/kg/day and 30 mg/kg/day linagliptin groups, respectively; compared with 20.9 mg/kg/minute with vehicle (P<0.001). Hepatic glucose production was significantly suppressed during the clamp: 4.7 mg/kg/minute and 2.1 mg/kg/minute in the 3 mg/kg/day and 30 mg/kg/day linagliptin groups, respectively; compared with 12.5 mg/kg/minute with vehicle (P<0.001). In addition, 30 mg/kg/day linagliptin treatment resulted in a significantly reduced number of macrophages infiltrating adipose tissue (P<0.05). Linagliptin treatment also decreased liver expression of PTP1B, SOCS3, SREBP1c, SCD-1 and FAS (P<0.05). Other tissues like muscle, heart and kidney were not significantly affected

  10. The cannabinoid Δ9-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity

    PubMed Central

    Wargent, E T; Zaibi, M S; Silvestri, C; Hislop, D C; Stocker, C J; Stott, C G; Guy, G W; Duncan, M; Di Marzo, V; Cawthorne, M A

    2013-01-01

    Background: Cannabinoid type-1 (CB1) receptor inverse agonists improve type 2 diabetes and dyslipidaemia but were discontinued due to adverse psychiatric effects. Δ9-Tetrahydrocannabivarin (THCV) is a neutral CB1 antagonist producing hypophagia and body weight reduction in lean mice. We investigated its effects in dietary-induced (DIO) and genetically (ob/ob) obese mice. Methods: We performed two dose-ranging studies in DIO mice; study 1: 0.3, 1, 2.5, 5 and 12.5 mg kg−1, oral twice daily for 30 days and study 2: 0.1, 0.5, 2.5 and 12.5 mg kg−1, oral, once daily for 45 days. One pilot (study 3: 0.3 and 3 mg kg−1, oral, once daily) and one full dose-ranging (study 4: 0.1, 0.5, 2.5 and 12.5 mg kg−1, oral, once daily) studies in ob/ob mice for 30 days. The CB1 inverse agonist, AM251, oral, 10 mg kg−1 once daily or 5 mg kg−1 twice daily was used as the positive control. Cumulative food and water intake, body weight gain, energy expenditure, glucose and insulin levels (fasting or during oral glucose tolerance tests), plasma high-density lipoprotein and total cholesterol, and liver triglycerides were measured. HL-5 hepatocytes or C2C12 myotubes made insulin-resistant with chronic insulin or palmitic acid were treated with 0, 1, 3 and 10 μℳ THCV or AM251. Results: THCV did not significantly affect food intake or body weight gain in any of the studies, but produced an early and transient increase in energy expenditure. It dose-dependently reduced glucose intolerance in ob/ob mice and improved glucose tolerance and increased insulin sensitivity in DIO mice, without consistently affecting plasma lipids. THCV also restored insulin signalling in insulin-resistant hepatocytes and myotubes. Conclusions: THCV is a new potential treatment against obesity-associated glucose intolerance with pharmacology different from that of CB1 inverse agonists/antagonists. PMID:23712280

  11. [Serum insulin, leptin and growth hormone levels are associated with body mass index and obesity index in adolescents].

    PubMed

    Molero-Conejo, Emperatriz; Morales, Luz Marina; Fernández, Virginia; Raleigh, Xiomara; Casanova, Angel; Connell, Lissette; Gómnez, Maria Esther; Ryder, Elena; Campos, Gilberto

    2006-03-01

    Leptin, insulin and growth hormone levels seem to regulate body composition, fat distribution and fat mass. The purpose of this study was to determine the relationship among insulin, leptin and growth hormone levels in a group of adolescents. Ninety five adolescents (31 boys and 64 girls) between 13 and 18 y. of age were studied. A medical and nutritional history was made which included body mass index (BMI) and subcutaneous skinfolds measurements. Basal levels of glucose, triglycerides, total cholesterol, HDL-C, LDL-C, VLDL-C, leptin, insulin and growth hormone were determined. The leptin and insulin levels were positively associated with body mass index (BMI) and obesity index (OBI). Insulin, leptin and obesity markers were negatively associated with growth hormone level. Fifty two percent of the adolescents with BMI = 21.09 kg/m2 were considered metabolically obese because they had elevated levels of insulin (18.68 +/- 1.52 vs. 10.08 +/- 0.38 microU/ml), HOMA IR (3.34 +/- 0.24 vs. 1.76 +/- 0.07), leptin (16.30 +/- 1.24 vs. 8.11 +/- 1.32 ng./dl) and triglycerides (78.56 +/- 4.38 vs. 64.39 +/- 5.48 mg/dl) and lower levels of HDL-C (39.09 +/- 1.27 vs. 43.30 +/- 2.38 mg/dl), compared with normal group. The same alterations were observed in the obese group, in which significative decrease in growth hormone level was added. We conclude that hyperinsulinemia, hyperleptinemia and low growth hormone levels, may be established as risk factors related to obesity markers, lipid alterations and insulin resistance that can lead to an early development of Type II diabetes and cardiovascular disease.

  12. Activation of placental insulin and mTOR signaling in a mouse model of maternal obesity associated with fetal overgrowth.

    PubMed

    Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2016-01-01

    Fetal overgrowth is common in obese women and is associated with perinatal complications and increased risk for the child to develop metabolic syndrome later in life. Placental nutrient transport capacity has been reported to be increased in obese women giving birth to large infants; however, the underlying mechanisms are not well established. Obesity in pregnancy is characterized by elevated maternal serum insulin and leptin, hormones that stimulate placental amino acid transporters in vitro. We hypothesized that maternal obesity activates placental insulin/IGF-I/mTOR and leptin signaling pathways. We tested this hypothesis in a mouse model of obesity in pregnancy that is associated with fetal overgrowth. C57BL/6J female mice were fed a control (C) or a high-fat/high-sugar (HF/HS) pelleted diet supplemented by ad libitum access to sucrose (20%) solution. Placentas were collected at embryonic day 18.5. Using Western blot analysis, placental mTOR activity was determined along with energy, inflammatory, leptin, and insulin signaling pathways (upstream modulators of mTOR). Phosphorylation of S6 ribosomal protein (S-235/236), 4E-BP1 (T-37/46), Insulin receptor substrate 1 (Y-608), Akt (T-308), and STAT-3 (Y-705) was increased in obese dams. In contrast, expression of placental caspase-1, IкBα, IL-1β, and phosphorylated-JNK(p46/54-T183/Y185) was unaltered. Fetal amino acid availability is a key determinant of fetal growth. We propose that activation of placental insulin/IGF-I/mTOR and leptin signaling pathways in obese mice stimulates placental amino acid transport and contributes to increased fetal growth.

  13. Assessment of 11-β hydroxysteroid dehydrogenase (11-βHSD1) 4478T>G and tumor necrosis factor-α (TNF-α)-308G>A polymorphisms with obesity and insulin resistance in Asian Indians in North India.

    PubMed

    Sharma, Mukti; Vikram, Naval Kishore; Misra, Anoop; Bhatt, SuryaPrakash; Tarique, Mohammed; Parray, Hilal Ahmad; Pandey, Ravindra Mohan; Luthra, Kalpana

    2013-11-01

    11-β hydroxysteroid dehydrogenase (11-βHSD1), tumor necrosis factor-α (TNF-α) and their role in obesity, regional adiposity and insulin resistance has been sparsely evaluated. We determined the polymorphic status of 11-βHSD1 4478T>G and TNF-α-308G>A in Asian Indians in north India. In this cross-sectional study (n = 498; 258 males, 240 females), association of genotypes (PCR–RFLP) of 11-βHSD1 and TNF-α were analyzed with obesity [BMI ≥ 25 kg/m(2), percentage body fat (%BF by DEXA); subcutaneous and intra-abdominal fat area (L(2-3) level by single slice MRI) in a sub sample] and insulin resistance. 46 percent subjects had generalized obesity, 55 % abdominal obesity and 23.8 % were insulin resistant. Frequencies (%) of [T/T] and [T/G] genotypes of 11-βHSD1 were 89.57 and 10.43 respectively. Homozygosity for 11-βHSD1 4478G/G was absent with no association with parameters of obesity and insulin resistance. Frequencies (%) of TNF-α [G] and [A] alleles were 88 and 12 respectively. Higher frequency of variant -308[A/A] was observed in females versus males (p = 0.01). Females with at least one single A allele of TNF-α-308G>A had significantly high %BF and total skinfold, whereas higher values of waist hip ratio, total cholesterol, triglycerides and VLDL were observed in males. Subjects with even a single A allele in TNF-α genotype showed higher subscapular skinfold predisposing them to truncal subcutaneous adiposity (p = 0.02). Our findings of association of TNF-α-308G>A variant in females with obesity indices suggests a gender-specific role of this polymorphism in obesity. High truncal subcutaneous adiposity is associated with A allele of TNF-α-308G>A in this population.

  14. Low CD36 and LOX-1 Levels and CD36 Gene Subexpression Are Associated with Metabolic Dysregulation in Older Individuals with Abdominal Obesity

    PubMed Central

    Castro-Albarran, Jorge; Sandoval-García, Flavio; Flores-Alvarado, Luis-Javier

    2016-01-01

    Background. Obesity study in the context of scavenger receptors has been linked to atherosclerosis. CD36 and LOX-1 are important, since they have been associated with atherogenic and metabolic disease but not fat redistribution. The aim of our study was to determinate the association between CD36 and LOX-1 in presence of age and abdominal obesity. Methods. This is a cross-sectional study that included 151 healthy individuals, clinically and anthropometrically classified into two groups by age (<30 and ≥30 years old) and abdominal obesity (according to World Health Organization guidelines). We excluded individuals with any chronic and metabolic illness, use of medication, or smoking. Fasting blood samples were taken to perform determination of CD36 mRNA expression by real-time PCR, lipid profile and metabolic and low grade inflammation markers by routine methods, and soluble scavenger receptors (CD36 and LOX-1) by ELISA. Results. Individuals ≥30 years old with abdominal obesity presented high atherogenic index, lower soluble scavenger receptor levels, and subexpression of CD36 mRNA (54% less). On the other hand, individuals <30 years old with abdominal adiposity presented higher levels in the same parameters, except LOX-1 soluble levels. Conclusion. In this study, individuals over 30 years of age presented low soluble scavenger receptors levels pattern and CD36 gene subexpression, which suggest the chronic metabolic dysregulation in abdominal obesity. PMID:27525284

  15. Low CD36 and LOX-1 Levels and CD36 Gene Subexpression Are Associated with Metabolic Dysregulation in Older Individuals with Abdominal Obesity.

    PubMed

    Madrigal-Ruíz, Perla-Monserrat; Navarro-Hernández, Rosa-Elena; Ruíz-Quezada, Sandra-Luz; Corona-Meraz, Fernanda-Isadora; Vázquez-Del Mercado, Mónica; Gómez-Bañuelos, Eduardo; Castro-Albarran, Jorge; Sandoval-García, Flavio; Flores-Alvarado, Luis-Javier; Martín-Marquez, Beatriz-Teresita

    2016-01-01

    Background. Obesity study in the context of scavenger receptors has been linked to atherosclerosis. CD36 and LOX-1 are important, since they have been associated with atherogenic and metabolic disease but not fat redistribution. The aim of our study was to determinate the association between CD36 and LOX-1 in presence of age and abdominal obesity. Methods. This is a cross-sectional study that included 151 healthy individuals, clinically and anthropometrically classified into two groups by age (<30 and ≥30 years old) and abdominal obesity (according to World Health Organization guidelines). We excluded individuals with any chronic and metabolic illness, use of medication, or smoking. Fasting blood samples were taken to perform determination of CD36 mRNA expression by real-time PCR, lipid profile and metabolic and low grade inflammation markers by routine methods, and soluble scavenger receptors (CD36 and LOX-1) by ELISA. Results. Individuals ≥30 years old with abdominal obesity presented high atherogenic index, lower soluble scavenger receptor levels, and subexpression of CD36 mRNA (54% less). On the other hand, individuals <30 years old with abdominal adiposity presented higher levels in the same parameters, except LOX-1 soluble levels. Conclusion. In this study, individuals over 30 years of age presented low soluble scavenger receptors levels pattern and CD36 gene subexpression, which suggest the chronic metabolic dysregulation in abdominal obesity.

  16. Adipose Tissue Overexpression of Vascular Endothelial Growth Factor Protects Against Diet-Induced Obesity and Insulin Resistance

    PubMed Central

    Elias, Ivet; Franckhauser, Sylvie; Ferré, Tura; Vilà, Laia; Tafuro, Sabrina; Muñoz, Sergio; Roca, Carles; Ramos, David; Pujol, Anna; Riu, Efren; Ruberte, Jesús; Bosch, Fatima

    2012-01-01

    During the expansion of fat mass in obesity, vascularization of adipose tissue is insufficient to maintain tissue normoxia. Local hypoxia develops and may result in altered adipokine expression, proinflammatory macrophage recruitment, and insulin resistance. We investigated whether an increase in adipose tissue angiogenesis could protect against obesity-induced hypoxia and, consequently, insulin resistance. Transgenic mice overexpressing vascular endothelial growth factor (VEGF) in brown adipose tissue (BAT) and white adipose tissue (WAT) were generated. Vessel formation, metabolism, and inflammation were studied in VEGF transgenic mice and wild-type littermates fed chow or a high-fat diet. Overexpression of VEGF resulted in increased blood vessel number and size in both WAT and BAT and protection against high-fat diet–induced hypoxia and obesity, with no differences in food intake. This was associated with increased thermogenesis and energy expenditure. Moreover, whole-body insulin sensitivity and glucose tolerance were improved. Transgenic mice presented increased macrophage infiltration, with a higher number of M2 anti-inflammatory and fewer M1 proinflammatory macrophages than wild-type littermates, thus maintaining an anti-inflammatory milieu that could avoid insulin resistance. These studies suggest that overexpression of VEGF in adipose tissue is a potential therapeutic strategy for the prevention of obesity and insulin resistance. PMID:22522611

  17. Abdominal adipose tissue: early metabolic dysfunction associated to insulin resistance and oxidative stress induced by an unbalanced diet.

    PubMed

    Rebolledo, O R; Marra, C A; Raschia, A; Rodriguez, S; Gagliardino, J J

    2008-11-01

    The possible contribution of early changes in lipid composition, function, and antioxidant status of abdominal adipose tissue (AAT) induced by a fructose-rich diet (FRD) to the development of insulin resistance (IR) and oxidative stress (OS) was studied. Wistar rats were fed with a commercial diet with (FRD) or without 10% fructose in the drinking water for 3 weeks. The glucose (G), triglyceride (TG), and insulin (I) plasma levels, and the activity of antioxidant enzymes, lyposoluble antioxidants, total glutathione (GSH), lipid peroxidation as TBARS, fatty acid (FA) composition of AAT-TG as well as their release by incubated pieces of AAT were measured. Rats fed with a FRD have significantly higher plasma levels of G, TG, and I. Their AAT showed a marked increase in content and ratios of saturated to monounsaturated and polyunsaturated FAs, TBARS, and catalase, GSH-transferase and GSH-reductase, together with a decrease in superoxide dismutase and GSH-peroxidase activity, and total GSH, alpha-tocopherol, beta-carotene and lycopene content. Incubated AAT from FRD released in vitro higher amount of free fatty acids (FFAs) with higher ratios of saturated to monounsaturated and polyunsaturated FAs. Our data suggest that FRD induced an early prooxidative state and metabolic dysfunction in AAT that would favor the overall development of IR and OS and further development of pancreatic beta-cell failure; therefore, its early control would represent an appropriate strategy to prevent alterations such as the development of type 2 diabetes.

  18. Takeaway food consumption and its associations with diet quality and abdominal obesity: a cross-sectional study of young adults

    PubMed Central

    Smith, Kylie J; McNaughton, Sarah A; Gall, Seana L; Blizzard, Leigh; Dwyer, Terence; Venn, Alison J

    2009-01-01

    Background Few studies have investigated the associations of takeaway food consumption with overall diet quality and abdominal obesity. Young adults are high consumers of takeaway food so we aimed to examine these associations in a national study of young Australian adults. Methods A national sample of 1,277 men and 1,585 women aged 26–36 completed a self-administered questionnaire on demographic and lifestyle factors, a 127 item food frequency questionnaire, usual daily frequency of fruit and vegetable consumption and usual weekly frequency of takeaway food consumption. Dietary intake was compared with the dietary recommendations from the Australian Guide to Healthy Eating. Waist circumference was measured for 1,065 men and 1,129 women. Moderate abdominal obesity was defined as ≥ 94 cm for men and ≥ 80 cm for women. Prevalence ratios (PR) were calculated using log binomial regression. Takeaway food consumption was dichotomised, with once a week or less as the reference group. Results Consumption of takeaway food twice a week or more was reported by more men (37.9%) than women (17.7%, P < 0.001). Compared with those eating takeaway once a week or less, men eating takeaway twice a week or more were significantly more likely to be single, younger, current smokers and spend more time watching TV and sitting, whereas women were more likely to be in the workforce and spend more time watching TV and sitting. Participants eating takeaway food at least twice a week were less likely (P < 0.05) to meet the dietary recommendation for vegetables, fruit, dairy, extra foods, breads and cereals (men only), lean meat and alternatives (women only) and overall met significantly fewer dietary recommendations (P < 0.001). After adjusting for confounding variables (age, leisure time physical activity, TV viewing and employment status), consuming takeaway food twice a week or more was associated with a 31% higher prevalence of moderate abdominal obesity in men (PR: 1.31; 95% CI: 1

  19. Combined effects of insulin treatment and adipose tissue-specific agouti expression on the development of obesity.

    PubMed

    Mynatt, R L; Miltenberger, R J; Klebig, M L; Zemel, M B; Wilkinson, J E; Wilkinson, W O; Woychik, R P

    1997-02-04

    The agouti gene product is a secreted protein that acts in a paracrine manner to regulate coat color in mammals. Several dominant mutations at the agouti locus in mice cause the ectopic, ubiquitous expression of agouti, resulting in a condition similar to adult-onset obesity and non-insulin-dependent diabetes mellitus. The human agouti protein is 85% homologous to mouse agouti; however, unlike the mouse agouti gene, human agouti is normally expressed in adipose tissue. To address whether expression of agouti in human adipose tissue is physiologically relevant, transgenic mice were generated that express agouti in adipose tissue. Similar to most humans, these mice do not become obese or diabetic. However, we found that daily insulin injections significantly increased weight gain in the transgenic lines expressing agouti in adipose tissue, but not in nontransgenic mice. These results suggest that insulin triggers the onset of obesity and that agouti expression in adipose tissue potentiates this effect. Accordingly, the investigation of agouti's role in obesity and non-insulin-dependent diabetes mellitus in mice holds significant promise for understanding the pathophysiology of human obesity.

  20. Circulating Zonulin, a Marker of Intestinal Permeability, Is Increased in Association with Obesity-Associated Insulin Resistance

    PubMed Central

    Moreno-Navarrete, José María; Sabater, Mònica; Ortega, Francisco; Ricart, Wifredo; Fernández-Real, José Manuel

    2012-01-01

    Zonulin is the only physiological mediator known to regulate intestinal permeability reversibly by modulating intercellular tight junctions. To investigate the relationship between intestinal permeability and obesity-associated metabolic disturbances in humans, we aimed to study circulating zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA) was measured in 123 caucasian men in association with inflammatory and metabolic parameters (including minimal model-measured insulin sensitivity). Circulating zonulin increased with body mass index (BMI), waist to hip ratio (WHR), fasting insulin, fasting triglycerides, uric acid and IL-6, and negatively correlated with HDL-cholesterol and insulin sensitivity. In multiple regression analysis, insulin sensitivity (p = 0.002) contributed independently to circulating zonulin variance, after controlling for the effects of BMI, fasting triglycerides and age. When circulating IL-6 was added to this model, only BMI (p = 0.01) contributed independently to circulating zonulin variance. In conclusion, the relationship between insulin sensitivity and circulating zonulin might be mediated through the obesity-related circulating IL-6 increase. PMID:22629362

  1. Does Insulin Explain the Relation between Maternal Obesity and Poor Lactation Outcomes? An Overview of the Literature1234

    PubMed Central

    2016-01-01

    It is well established that obese women are at increased risk of delayed lactogenesis and short breastfeeding duration, but the underlying causal contributors remain unclear. This review summarizes the literature examining the role of insulin in lactation outcomes. Maternal obesity is a strong risk factor for insulin resistance and prediabetes, but until recently a direct role for insulin in milk production had not been elucidated. Over the past 6 y, studies in both animal models and humans have shown insulin-sensitive gene expression to be dramatically upregulated specifically during the lactation cycle. Insulin is now considered to play a direct role in lactation, including essential roles in secretory differentiation, secretory activation, and mature milk production. At the same time, emerging clinical research suggests an important association between suboptimal glucose tolerance and lactation difficulty. To develop effective interventions to support lactation success in obese women further research is needed to identify how, when, and for whom maternal insulin secretion and sensitivity affect lactation ability. PMID:26980825

  2. Obesity in MENX Rats Is Accompanied by High Circulating Levels of Ghrelin and Improved Insulin Sensitivity.

    PubMed

    Wiedemann, Tobias; Bielohuby, Maximilian; Müller, Timo D; Bidlingmaier, Martin; Pellegata, Natalia S

    2016-02-01

    Ghrelin, the natural ligand of the growth hormone secretagogue receptor type 1a (GHS-R1a), is mainly secreted from the stomach and regulates food intake and energy homeostasis. p27 regulates cell cycle progression in many cell types. Here, we report that rats affected by the multiple endocrine neoplasia syndrome MENX, caused by a p27 mutation, develop pancreatic islet hyperplasia containing elevated numbers of ghrelin-producing ε-cells. The metabolic phenotype of MENX-affected rats featured high endogenous acylated and unacylated plasma ghrelin levels. Supporting increased ghrelin action, MENX rats show increased food intake, enhanced body fat mass, and elevated plasma levels of triglycerides and cholesterol. Ghrelin effect on food intake was confirmed by treating MENX rats with a GHS-R1a antagonist. At 7.5 months, MENX-affected rats show decreased mRNA levels of hypothalamic GHS-R1a, neuropeptide Y (NPY), and agouti-related protein (AgRP), suggesting that prolonged hyperghrelinemia may lead to decreased ghrelin efficacy. In line with ghrelin's proposed role in glucose metabolism, we find decreased glucose-stimulated insulin secretion in MENX rats, while insulin sensitivity is improved. In summary, we provide a novel nontransgenic rat model with high endogenous ghrelin plasma levels and, interestingly, improved glucose tolerance. This model might aid in identifying new therapeutic approaches for obesity and obesity-related diseases, including type 2 diabetes.

  3. Low Insulin-Like Growth Factor-1 Level in Obesity Nephropathy: A New Risk Factor?

    PubMed Central

    Bancu, Ioana; Navarro Díaz, Maruja; Serra, Assumpta; Granada, Marisa; Lopez, Dolores; Romero, Ramon; Bonet, Josep

    2016-01-01

    Introduction IGF-1 (insulin-like growth factor-1) is a hormone involved in cell growth and other important processes. In the kidney, IGF-1 has a stimulating effect, increasing the blood flow and glomerular filtration rate. Although many experimental animal studies regarding the role of IGF-1 in the kidney have been conducted, few human studies are available in the literature. Obesity is a cause of renal failure, and several glomerular lesions associated with obesity have been described. However, no studies regarding the levels of IGF-1 in morbidly obese patients with renal injury associated with obesity have been conducted. Aim To determine the serum IGF-1 concentrations in morbidly obese patients with normal renal function but with different types of early obesity-related glomerular lesions and to evaluate the possible relationship between IGF-1 and the presence of renal lesions. Methods Eighty morbidly obese patients with renal biopsy, including 11 patients with no evidence of renal lesion, 17 patients with single glomerulomegaly, 21 patients with single podocyte hypertrophy, 10 patients with glomerulomegaly and podocyte hypertrophy, 5 patients with focal segmental hyalinosis, and 16 patients with increased mesangial matrix and/or mesangial proliferation, participated in this study. Biological parameters, including serum IGF-1 concentrations with the standard deviation score for age (SDS-IGF-1), were determined for all patients. Results Eighty patients (50 women and 30 men) with a mean BMI of 52.63 ± 8.71 and a mean age of 42.40 ± 9.45 years were included in this study. IGF-1, IGF-1 SDS and IGF-1BP3 levels according to the renal injury were compared (normal glomeruli: IGF-1 = 190.17 ± 72.46; glomerulomegaly: IGF-1 = 122.3 ± 50.05; podocyte hypertrophy: IGF-1 = 119.81 ± 60.34; focal segmental hyalinosis: IGF-1 170.98 ± 100.83, increased mesangial matrix and/or mesangial proliferation: IGF-1 117.73 ± 63.87). Statistically significant differences were

  4. Inverse Relationship of the CMKLR1 Relative Expression and Chemerin Serum Levels in Obesity with Dysmetabolic Phenotype and Insulin Resistance

    PubMed Central

    Corona-Meraz, Fernanda-Isadora; Navarro-Hernández, Rosa-Elena; Ruíz-Quezada, Sandra-Luz; Madrigal-Ruíz, Perla-Monserrat; Castro-Albarrán, Jorge; Chavarría-Ávila, Efraín; Guzmán-Ornelas, Milton-Omar; Gómez-Bañuelos, Eduardo; Petri, Marcelo-Herón; Ramírez-Cedano, Joel-Isidro; Aguilar-Aldrete, María-Elena; Ríos-Ibarra, Clara; Vázquez-Del Mercado, Mónica

    2016-01-01

    Background. In obesity there is a subclinical chronic low-grade inflammatory response where insulin resistance (IR) may develop. Chemerin is secreted in white adipose tissue and promotes low-grade inflammatory process, where it expressed CMKLR1 receptor. The role of chemerin and CMKLR1 in inflammatory process secondary to obesity is not defined yet. Methods. Cross-sectional study with 134 individuals classified as with and without obesity by body mass index (BMI) and IR. Body fat storage measurements and metabolic and inflammatory markers were measured by routine methods. Soluble chemerin and basal levels of insulin by ELISA and relative expression of CMKLR1 were evaluated with qPCR and 2−ΔΔCT method. Results. Differences (P < 0.05) were observed between obesity and lean individuals in body fat storage measurements and metabolic-inflammatory markers. Both CMKLR1 expression and chemerin levels were increased in obesity without IR. Soluble chemerin levels correlate with adiposity and metabolic markers (r = 8.8% to 38.5%), P < 0.05. Conclusion. The increment of CMKLR1 expression was associated with insulin production. Increased serum levels of chemerin in obesity were observed, favoring a dysmetabolic response. The results observed in this study suggest that both chemerin and CMKLR1 have opposite expression in the context of low-grade inflammatory response manifested in the development of IR. PMID:27239101

  5. Insulin Production and Resistance in Different Models of Diet-Induced Obesity and Metabolic Syndrome

    PubMed Central

    Alwahsh, Salamah M.; Dwyer, Benjamin J.; Forbes, Shareen; van Thiel, David H.; Starkey Lewis, Philip J.; Ramadori, Giuliano

    2017-01-01

    The role of the liver and the endocrine pancreas in development of hyperinsulinemia in different types of obesity remains unclear. Sedentary rats (160 g) were fed a low-fat-diet (LFD, chow 13% kcal fat), high-fat-diet (HFD, 35% fat), or HFD+ 30% ethanol+ 30% fructose (HF-EFr, 22% fat). Overnight-fasted rats were culled after one, four or eight weeks. Pancreatic and hepatic mRNAs were isolated for subsequent RT-PCR analysis. After eight weeks, body weights increased three-fold in the LFD group, 2.8-fold in the HFD group, and 2.4-fold in the HF-EFr (p < 0.01). HF-EFr-fed rats had the greatest liver weights and consumed less food during Weeks 4–8 (p < 0.05). Hepatic-triglyceride content increased progressively in all groups. At Week 8, HOMA-IR values, fasting serum glucose, C-peptide, and triglycerides levels were significantly increased in LFD-fed rats compared to that at earlier time points. The greatest plasma levels of glucose, triglycerides and leptin were observed in the HF-EFr at Week 8. Gene expression of pancreatic-insulin was significantly greater in the HFD and HF-EFr groups versus the LFD. Nevertheless, insulin: C-peptide ratios and HOMA-IR values were substantially higher in HF-EFr. Hepatic gene-expression of insulin-receptor-substrate-1/2 was downregulated in the HF-EFr. The expression of phospho-ERK-1/2 and inflammatory-mediators were greatest in the HF-EFr-fed rats. Chronic intake of both LFD and HFD induced obesity, MetS, and intrahepatic-fat accumulation. The hyperinsulinemia is the strongest in rats with the lowest body weights, but having the highest liver weights. This accompanies the strongest increase of pancreatic insulin production and the maximal decrease of hepatic insulin signaling, which is possibly secondary to hepatic fat deposition, inflammation and other factors. PMID:28134848

  6. The effects of a soluble activin type IIB receptor on obesity and insulin sensitivity

    PubMed Central

    Akpan, Imo; Goncalves, Marcus D.; Dhir, Ravindra; Yin, Xiaoyan; Pistilli, Emidio; Bogdanovich, Sasha; Khurana, Tejvir; Ucran, Jeffrey; Lachey, Jennifer; Ahima, Rexford S.

    2009-01-01

    Myostatin, also known as Growth and Differentiation Factor 8, is a secreted protein that inhibits muscle growth. Disruption of myostatin signaling increases muscle mass and decreases glucose, but it is unclear whether these changes are related. We treated mice on chow and high-fat diets with a soluble activin receptor type IIB (ActRIIB.Fc) which is a putative endogenous signaling receptor for myostatin and other ligands of the TGF-β superfamily. After 4 weeks, RAP-031 increased lean and muscle mass, grip strength, and contractile force. RAP-031 enhanced the ability of insulin to suppress glucose production under clamp conditions in high-fat fed mice, but did not significantly change insulin-mediated glucose disposal. The hepatic insulin sensitizing effect of RAP-031 treatment was associated with increased adiponectin levels. RAP-031 treatment for 10 weeks further increased muscle mass and drastically reduced fat content in mice on either chow or high-fat diet. RAP-031 suppressed hepatic glucose production and increased peripheral glucose uptake in chow fed mice. In contrast, RAP-031 suppressed glucose production with no apparent change in glucose disposal in high-fat diet mice. Our findings demonstrate that disruption of ActRIIB signaling is a viable pharmacological approach for treating obesity and diabetes. PMID:19668253

  7. Decaffeinated green coffee bean extract attenuates diet-induced obesity and insulin resistance in mice.

    PubMed

    Song, Su Jin; Choi, Sena; Park, Taesun

    2014-01-01

    This study investigated whether decaffeinated green coffee bean extract prevents obesity and improves insulin resistance and elucidated its mechanism of action. Male C57BL/6N mice (N = 48) were divided into six dietary groups: chow diet, HFD, HFD-supplemented with 0.1%, 0.3%, and 0.9% decaffeinated green coffee bean extract, and 0.15% 5-caffeoylquinic acid. Based on the reduction in HFD-induced body weight gain and increments in plasma lipids, glucose, and insulin levels, the minimum effective dose of green coffee bean extract appears to be 0.3%. Green coffee bean extract resulted in downregulation of genes involved in WNT10b- and galanin-mediated adipogenesis and TLR4-mediated proinflammatory pathway and stimulation of GLUT4 translocation to the plasma membrane in white adipose tissue. Taken together, decaffeinated green coffee bean extract appeared to reverse HFD-induced fat accumulation and insulin resistance by downregulating the genes involved in adipogenesis and inflammation in visceral adipose tissue.

  8. Adenylyl cyclase 3 haploinsufficiency confers susceptibility to diet-induced obesity and insulin resistance in mice

    PubMed Central

    Tong, Tao; Shen, Ying; Lee, Han-Woong; Yu, Rina; Park, Taesun

    2016-01-01

    Adenylyl cyclase 3 (Adcy3), a member of the mammalian adenylyl cyclase family responsible for generating the second messenger cAMP, has long been known to play an essential role in olfactory signal transduction. Here, we demonstrated that Adcy3 heterozygous null mice displayed increased visceral adiposity in the absence of hyperphagia and developed abnormal metabolic features characterized by impaired insulin sensitivity, dyslipidemia, and increased plasma levels of proinflammatory cytokines on both chow and high-fat diet (HFD). Of note, HFD decreased the Adcy3 expression in white adipose tissue, liver, and muscle. We also report for the first time that Adcy3 haploinsufficiency resulted in reduced expression of genes involved in thermogenesis, fatty acid oxidation, and insulin signaling, with enhanced expression of genes related to adipogenesis in peripheral tissues of mice. In conclusion, these findings suggest that cAMP signals generated by Adcy3 in peripheral tissues may play a pivotal role in modulating obesity and insulin sensitivity. PMID:27678003

  9. Lemon balm extract causes potent antihyperglycemic and antihyperlipidemic effects in insulin-resistant obese mice.

    PubMed

    Weidner, Christopher; Wowro, Sylvia J; Freiwald, Anja; Kodelja, Vitam; Abdel-Aziz, Heba; Kelber, Olaf; Sauer, Sascha

    2014-04-01

    Over the last decades polyetiological metabolic diseases such as obesity and type 2 diabetes have emerged as a global epidemic. Efficient strategies for prevention and treatment include dietary intervention and the development of validated nutraceuticals. Safe extracts of edible plants provide a resource of structurally diverse molecules that can effectively interfere with multifactorial diseases. In this study, we describe the application of ethanolic lemon balm (Melissa officinalis) leaves extract for the treatment of insulin-resistance and dyslipidemia in mice. We show that lemon balm extract (LBE) activates the peroxisome proliferator-activated receptors (PPARs), which have key roles in the regulation of whole body glucose and lipid metabolism. Application of LBE (0.6 mg/mL) to human primary adipocytes resulted in specific peroxisome proliferator-activated receptor target gene expression. LBE treatment of insulin-resistant high-fat diet-fed C57BL/6 mice (200 mg/kg/day) for 6 weeks considerably reduced hyperglycemia and insulin resistance, plasma triacylglycerol, nonesterified fatty acids and LDL/VLDL cholesterol levels. Taken together, ethanolic lemon balm extract can potentially be used to prevent or concomitantly treat type 2 diabetes and associated disorders such as dyslipidemia and hypercholesterolemia.

  10. Polycystic Ovary Syndrome, Insulin Resistance, and Obesity: Navigating the Pathophysiologic Labyrinth

    PubMed Central

    Rojas, Joselyn; Chávez, Mervin; Olivar, Luis; Rojas, Milagros; Morillo, Jessenia; Mejías, José; Calvo, María; Bermúdez, Valmore

    2014-01-01

    Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR), and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome. PMID:25763405

  11. Genetic ablation of lymphocytes and cytokine signaling in nonobese diabetic mice prevents diet-induced obesity and insulin resistance

    PubMed Central

    Friedline, Randall H.; Ko, Hwi Jin; Jung, Dae Young; Lee, Yongjin; Bortell, Rita; Dagdeviren, Sezin; Patel, Payal R.; Hu, Xiaodi; Inashima, Kunikazu; Kearns, Caitlyn; Tsitsilianos, Nicholas; Shafiq, Umber; Shultz, Leonard D.; Lee, Ki Won; Greiner, Dale L.; Kim, Jason K.

    2016-01-01

    Obesity is characterized by a dysregulated immune system, which may causally associate with insulin resistance and type 2 diabetes. Despite widespread use of nonobese diabetic (NOD) mice, NOD with severe combined immunodeficiency (scid) mutation (SCID) mice, and SCID bearing a null mutation in the IL-2 common γ chain receptor (NSG) mice as animal models of human diseases including type 1 diabetes, the underlying metabolic effects of a genetically altered immune system are poorly understood. For this, we performed a comprehensive metabolic characterization of these mice fed chow or after 6 wk of a high-fat diet. We found that NOD mice had ∼50% less fat mass and were 2-fold more insulin sensitive, as measured by hyperinsulinemic-euglycemic clamp, than C57BL/6 wild-type mice. SCID mice were also more insulin sensitive with increased muscle glucose metabolism and resistant to diet-induced obesity due to increased energy expenditure (∼10%) and physical activity (∼40%) as measured by metabolic cages. NSG mice were completely protected from diet-induced obesity and insulin resistance with significant increases in glucose metabolism in peripheral organs. Our findings demonstrate an important role of genetic background, lymphocytes, and cytokine signaling in diet-induced obesity and insulin resistance.—Friedline, R. H., Ko, H. J., Jung, D. Y., Lee, Y., Bortell, R., Dagdeviren, S., Patel, P. R., Hu, X., Inashima, K., Kearns, C., Tsitsilianos, N., Shafiq, U., Shultz, L. D., Lee, K. W., Greiner, D. L., Kim, J. K. Genetic ablation of lymphocytes and cytokine signaling in nonobese diabetic mice prevents diet-induced obesity and insulin resistance. PMID:26644351

  12. Insulin Resistance, Dyslipidemia and Cardiovascular Changes in a Group of Obese Children.

    PubMed

    Pires, António; Martins, Paula; Pereira, Ana Margarida; Silva, Patricia Vaz; Marinho, Joana; Marques, Margarida; Castela, Eduardo; Sena, Cristina; Seiça, Raquel

    2015-01-23

    Introduction: Obesity-related comorbidities are present in young obese children, providing a platform for early adult cardiovascular disorders. Objectives: To compare and correlate markers of adiposity to metabolic disturbances, vascular and cardiac morphology in a European pediatric obese cohort. Methods: We carried out an observational and transversal analysis in a cohort consisting of 121 obese children of both sexes, between the ages of 6 and 17 years. The control group consisted of 40 children with normal body mass index within the same age range. Markers of adiposity, plasma lipids and lipoproteins, homeostasis model assessment-insulin resistance, common carotid artery intima-media thickness and left ventricular diameters were analyzed. Results: There were statistically significant differences between the control and obese groups for the variables analyzed, all higher in the obese group, except for age, high-density lipoprotein cholesterol and adiponectin, higher in the control group. In the obese group, body mass index was directly correlated to left ventricular mass (r=0.542; p=0.001), the homeostasis model assessment-insulin resistance (r=0.378; p=<0.001) and mean common carotid artery intima-media thickness (r=0.378; p=<0.001). In that same group, insulin resistance was present in 38.1%, 12.5% had a combined dyslipidemic pattern, and eccentric hypertrophy was the most common left ventricular geometric pattern. Conclusions: These results suggest that these markers may be used in clinical practice to stratify cardiovascular risk, as well as to assess the impact of weight control programs.Fundamento: As comorbidades relacionadas com a obesidade encontram-se patentes em crianças jovens obesas e são, potencialmente, um ponto de partida para as doenças cardiovasculares em adultos jovens. Objetivos: Comparar e correlacionar marcadores de adiposidade com distúrbios metabólicos e alterações cardiovasculares numa coorte de crianças obesas europeias. M

  13. Bif-1 deficiency impairs lipid homeostasis and causes obesity accompanied by insulin resistance.

    PubMed

    Liu, Ying; Takahashi, Yoshinori; Desai, Neelam; Zhang, Jun; Serfass, Jacob M; Shi, Yu-Guang; Lynch, Christopher J; Wang, Hong-Gang

    2016-02-09

    Bif-1 is a membrane-curvature inducing protein that is implicated in the regulation of autophagy and tumorigenesis. Here, we report that Bif-1 plays a critical role in regulating lipid catabolism to control the size of lipid droplets and prevent the development of obesity and insulin resistance upon aging or dietary challenge. Our data show that Bif-1 deficiency promotes the expansion of adipose tissue mass without altering food intake or physical activities. While Bif-1 is dispensable for adipose tissue development, its deficiency reduces the basal rate of adipose tissue lipolysis and results in adipocyte hypertrophy upon aging. The importance of Bif-1 in lipid turnover is not limited to adipose tissue since fasting and refeeding-induced lipid droplet clearance is also attenuated by Bif-1 loss in the liver. Interestingly, obesity induced by a high fat-diet or Bif-1 deficiency downregulates the expression of proteins involved in the autophagy-lysosomal pathway, including Atg9a and Lamp1 in the adipose tissue. These findings thus identify Bif-1 as a novel regulator of lipid homeostasis to prevent the pathogenesis of obesity and its associated metabolic complications.

  14. Pregnancy, obesity and insulin resistance: maternal overnutrition and the target windows of fetal development.

    PubMed

    Muhlhausler, Beverly S; Gugusheff, Jessica R; Ong, Zhi Yi; Vithayathil, Mini A

    2013-09-01

    A substantial body of literature has demonstrated that the nutritional environment an individual experiences before birth or in early infancy is a key determinant of their health outcomes across the life course. This concept, the developmental origins of health and disease (DOHaD) hypothesis, was initially focused on the adverse consequences of exposure to a suboptimal nutrient supply and provided evidence that maternal undernutrition, fetal growth restriction, and low birth weight were associated with heightened risk of central adiposity, insulin resistance, and cardiovascular disease. More recently, the epidemic rise in the incidence of maternal obesity has seen the attention of the DOHaD field turn toward identifying the impact on the offspring of exposure to an excess nutrient supply in early life. The association between maternal obesity and increased risk of obesity in the offspring has been documented in human populations worldwide, and animal models have provided critical insights into the biological mechanisms that drive this relationship. This review will discuss the important roles that programming of the adipocyte and programming of the central neural networks which control appetite and reward play in the early life programming of metabolic disease by maternal overnutrition. It will also highlight the important research gaps and challenges that remain to be addressed and provide a personal perspective on where the field should be heading in the coming 5-10 years.

  15. Association of neck circumference with general and abdominal obesity in children and adolescents: the weight disorders survey of the CASPIAN-IV study

    PubMed Central

    Kelishadi, Roya; Djalalinia, Shirin; Motlagh, Mohammad Esmaiel; Rahimi, Ali; Bahreynian, Maryam; Arefirad, Tahereh; Ardalan, Gelayol; Safiri, Saeid; Hasani, Motahare; Asayesh, Hamid; Mansourian, Morteza; Qorbani, Mostafa

    2016-01-01

    Objectives This study aimed to evaluate the association of neck circumference (NC) with obesity to determine the sex-specific and age-specific optimal cut-off points of this measure in association with obesity in a national sample of the Iranian paediatric population. Methods This survey on weight disorders was conducted among a national sample of Iranian children and adolescents, aged 6–18 years. Using the area under the curve (AUC) of the receiver operator characteristic curves, we evaluated the association of NC with general and abdominal obesity. Results This national survey was conducted among 23 043 school students (50.8% boys) with a mean age (SD) of 12.55 (3.31) years. A significant association was documented between NC and other anthropometric measures in both sexes and in the whole population. In all age groups and genders, NC performed relatively well in classifying participants to overweight (AUC: 0.67 to 0.75, p<0.001), general obesity (AUC: 0.81 to 0.85, p<0.001) and abdominal obesity (AUC: 0.73 to 0.78, p<0.001). Conclusions NC can be considered as a simple time-saving clinical tool for obesity detection in large population-based studies in children and adolescents. It is significantly correlated with indices of adiposity and can reliably identify children with general and abdominal obesity in the Iranian paediatric population. PMID:27694487

  16. [Peculiarities of cardiovascular syndrome in children and adolescents with obesity in dependence of level of insulin resistance].

    PubMed

    Bekezin, V V; Kozlova, L V; Kozlova, I S; Igolkina, M V

    2008-01-01

    We conducted complex study of the state of cardiovascular system in 157 children aged 11-16 years with I-III degree obesity. Dazing on the results it is suggested to include in cardiovascular syndrome in children with obesity together with arterial hypertension syndrome of vegetative (autonomic) dysfunction, manifesting by disturbance of heart rate variability, endothelial dysfunction as well as systolic-diastolic dysfunction of the left ventricle. Degree of severity of impairment of cardiovascular system in children and adolescents with obesity depends on the level of insulin resistance.

  17. Vitamin E and vitamin C do not reduce insulin sensitivity but inhibit mitochondrial protein expression in exercising obese rats

    PubMed Central

    Picklo, Matthew J.; Thyfault, John P.

    2016-01-01

    Controversy exists as to whether supplementation with the antioxidants vitamin E and vitamin C blocks adaptation to exercise. Exercise is a first-line means to treat obesity and its complications. While diet-induced obesity alters mitochondrial function and induces insulin resistance (IR), no data exist as to whether supplementation with vitamin E and vitamin C modify responses to exercise in pre-existing obesity. We tested the hypothesis that dietary supplementation with vitamin E (0.4 g α-tocopherol acetate/kg) and vitamin C (0.5 g/kg) blocks exercise-induced improvements on IR and mitochondrial content in obese rats maintained on a high-fat (45% fat energy (en)) diet. Diet-induced obese, sedentary rats had a 2-fold higher homeostasis model assessment of insulin resistance and larger insulin area under the curve following glucose tolerances test than rats fed a low-fat (10% fat en) diet. Exercising (12 weeks at 5 times per week in a motorized wheel) of obese rats normalized IR indices, an effect not modified by vitamin E and vitamin C. Vitamin E and vitamin C supplementation with exercise elevated mtDNA content in adipose and skeletal muscle to a greater extent (20%) than exercise alone in a depot-specific manner. On the other hand, vitamin C and vitamin E decreased exercise-induced increases in mitochondrial protein content for complex I (40%) and nicotinamide nucleotide transhydrogenase (35%) in a muscle-dependent manner. These data indicate that vitamin E and vitamin C supplementation in obese rodents does not modify exercise-induced improvements in insulin sensitivity but that changes in mitochondrial biogenesis and mitochondrial protein expression may be modified by antioxidant supplementation. PMID:25761734

  18. A Lower-Carbohydrate, Higher-Fat Diet Reduces Abdominal and Intermuscular Fat and Increases Insulin Sensitivity in Adults at Risk of Type 2 Diabetes123

    PubMed Central

    Gower, Barbara A; Goss, Amy M

    2015-01-01

    Background: Obesity, particularly visceral and ectopic adiposity, increases the risk of type 2 diabetes. Objective: The aim of this study was to determine if restriction of dietary carbohydrate is beneficial for body composition and metabolic health. Methods: Two studies were conducted. In the first, 69 overweight/obese men and women, 53% of whom were European American (EA) and 47% of whom were African American (AA), were provided with 1 of 2 diets (lower-fat diet: 55%, 18%, and 27% of energy from carbohydrate, protein, and fat, respectively; lower-carbohydrate diet: 43%, 18%, and 39%, respectively) for 8 wk at a eucaloric level and 8 wk at a hypocaloric level. In the second study, 30 women with polycystic ovary syndrome (PCOS) were provided with 2 diets (lower-fat diet: 55%, 18%, and 27% of energy from carbohydrate, protein, and fat, respectively; lower-carbohydrate diet: 41%, 19%, and 40%, respectively) at a eucaloric level for 8 wk in a random-order crossover design. Results: As previously reported, among overweight/obese adults, after the eucaloric phase, participants who consumed the lower-carbohydrate vs. the lower-fat diet lost more intra-abdominal adipose tissue (IAAT) (11 ± 3% vs. 1 ± 3%; P < 0.05). After weight loss, participants who consumed the lower-carbohydrate diet had 4.4% less total fat mass. Original to this report, across the entire 16-wk study, AAs lost more fat mass with a lower-carbohydrate diet (6.2 vs. 2.9 kg; P < 0.01), whereas EAs showed no difference between diets. As previously reported, among women with PCOS, the lower-carbohydrate arm showed decreased fasting insulin (−2.8 μIU/mL; P < 0.001) and fasting glucose (−4.7 mg/dL; P < 0.01) and increased insulin sensitivity (1.06 arbitrary units; P < 0.05) and “dynamic” β-cell response (96.1 · 109; P < 0.001). In the lower-carbohydrate arm, women lost both IAAT (−4.8 cm2; P < 0.01) and intermuscular fat (−1.2 cm2; P < 0.01). In the lower-fat arm, women lost lean mass (−0

  19. Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independently of obesity

    PubMed Central

    Scott, Robert A; Fall, Tove; Pasko, Dorota; Barker, Adam; Sharp, Stephen J; Arriola, Larraitz; Balkau, Beverley; Barricarte, Aurelio; Barroso, Inês; Boeing, Heiner; Clavel-Chapelon, Françoise; Crowe, Francesca L; Dekker, Jacqueline M; Fagherazzi, Guy; Ferrannini, Ele; Forouhi, Nita G; Franks, Paul W; Gavrila, Diana; Giedraitis, Vilmantas; Grioni, Sara; Groop, Leif C; Kaaks, Rudolf; Key, Timothy J; Kühn, Tilman; Lotta, Luca A; Nilsson, Peter M; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Quirós, J. Ramón; Rolandsson, Olov; Roswall, Nina; Sacerdote, Carlotta; Sala, Núria; Sánchez, María-José; Schulze, Matthias B; Siddiq, Afshan; Slimani, Nadia; Sluijs, Ivonne; Spijkerman, Annemieke MW; Tjonneland, Anne; Tumino, Rosario; van der A, Daphne L; Yaghootkar, Hanieh; McCarthy, Mark I; Semple, Robert K; Riboli, Elio; Walker, Mark; Ingelsson, Erik; Frayling, Tim M; Savage, David B

    2014-01-01

    We aimed to validate genetic variants as instruments for insulin resistance and secretion, to characterise their association with intermediate phenotypes, and to investigate their role in T2D risk among normal-weight, overweight and obese individuals.We investigated the association of genetic scores with euglycaemic-hyperinsulinaemic clamp- and OGTT-based measures of insulin resistance and secretion, and a range of metabolic measures in up to 18,565 individuals. We also studied their association with T2D risk among normal-weight, overweight and obese individuals in up to 8,124 incident T2D cases. The insulin resistance score was associated with lower insulin sensitivity measured by M/I value (β in SDs-per-allele [95%CI]:−0.03[−0.04,−0.01];p=0.004). This score was associated with lower BMI (−0.01[−0.01,−0.0;p=0.02) and gluteofemoral fat-mass (−0.03[−0.05,−0.02;p=1.4×10−6), and with higher ALT (0.02[0.01,0.03];p=0.002) and gamma-GT (0.02[0.01,0.03];p=0.001). While the secretion score had a stronger association with T2D in leaner individuals (pinteraction=0.001), we saw no difference in the association of the insulin resistance score with T2D among BMI- or waist-strata(pinteraction>0.31). While insulin resistance is often considered secondary to obesity, the association of the insulin resistance score with lower BMI and adiposity and with incident T2D even among individuals of normal weight highlights the role of insulin resistance and ectopic fat distribution in T2D, independently of body size. PMID:24947364

  20. Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independent of obesity.

    PubMed

    Scott, Robert A; Fall, Tove; Pasko, Dorota; Barker, Adam; Sharp, Stephen J; Arriola, Larraitz; Balkau, Beverley; Barricarte, Aurelio; Barroso, Inês; Boeing, Heiner; Clavel-Chapelon, Françoise; Crowe, Francesca L; Dekker, Jacqueline M; Fagherazzi, Guy; Ferrannini, Ele; Forouhi, Nita G; Franks, Paul W; Gavrila, Diana; Giedraitis, Vilmantas; Grioni, Sara; Groop, Leif C; Kaaks, Rudolf; Key, Timothy J; Kühn, Tilman; Lotta, Luca A; Nilsson, Peter M; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Quirós, J Ramón; Rolandsson, Olov; Roswall, Nina; Sacerdote, Carlotta; Sala, Núria; Sánchez, María-José; Schulze, Matthias B; Siddiq, Afshan; Slimani, Nadia; Sluijs, Ivonne; Spijkerman, Annemieke M W; Tjonneland, Anne; Tumino, Rosario; van der A, Daphne L; Yaghootkar, Hanieh; McCarthy, Mark I; Semple, Robert K; Riboli, Elio; Walker, Mark; Ingelsson, Erik; Frayling, Tim M; Savage, David B; Langenberg, Claudia; Wareham, Nicholas J

    2014-12-01

    We aimed to validate genetic variants as instruments for insulin resistance and secretion, to characterize their association with intermediate phenotypes, and to investigate their role in type 2 diabetes (T2D) risk among normal-weight, overweight, and obese individuals. We investigated the association of genetic scores with euglycemic-hyperinsulinemic clamp- and oral glucose tolerance test-based measures of insulin resistance and secretion and a range of metabolic measures in up to 18,565 individuals. We also studied their association with T2D risk among normal-weight, overweight, and obese individuals in up to 8,124 incident T2D cases. The insulin resistance score was associated with lower insulin sensitivity measured by M/I value (β in SDs per allele [95% CI], -0.03 [-0.04, -0.01]; P = 0.004). This score was associated with lower BMI (-0.01 [-0.01, -0.0]; P = 0.02) and gluteofemoral fat mass (-0.03 [-0.05, -0.02; P = 1.4 × 10(-6)) and with higher alanine transaminase (0.02 [0.01, 0.03]; P = 0.002) and γ-glutamyl transferase (0.02 [0.01, 0.03]; P = 0.001). While the secretion score had a stronger association with T2D in leaner individuals (Pinteraction = 0.001), we saw no difference in the association of the insulin resistance score with T2D among BMI or waist strata (Pinteraction > 0.31). While insulin resistance is often considered secondary to obesity, the association of the insulin resistance score with lower BMI and adiposity and with incident T2D even among individuals of normal weight highlights the role of insulin resistance and ectopic fat distribution in T2D, independently of body size.

  1. Plasma fatty acid composition, estimated desaturase activities, and intakes of energy and nutrient in Japanese men with abdominal obesity or metabolic syndrome.

    PubMed

    Kawashima, Aiko; Sugawara, Shiori; Okita, Misako; Akahane, Takemi; Fukui, Kennichi; Hashiuchi, Maiko; Kataoka, Chieko; Tsukamoto, Ikuyo

    2009-01-01

    To examine predictive factors for abdominal obesity or metabolic syndrome, we investigated the association of plasma fatty acid composition, estimated desaturase activity, and nutrient intakes, with abdominal obesity or metabolic syndrome in Japanese males. Clinical characteristics, the fatty acid composition of plasma cholesteryl esters, and energy and nutrient intakes were analyzed in 3 groups: metabolic syndrome (MS, n=24), abdominal obesity (OB, n=43), and control (n=27). The estimated desaturase activities were calculated by the ratio of 16:1n-7/16:0, 18:3n-6/18:2n-6, and 20:4n-6/20:3n-6 in plasma cholesteryl esters as surrogates of the measure of the delta 9, delta 6, delta 5 desaturase (D9-16D, D6D and D5D) activities, respectively. Plasma fatty acid composition did not differ significantly between the OB group and the control group. The MS group had higher levels of palmitoleic, oleic, and gamma-linolenic acids, but a lower level of linoleic acid than the control. Stronger D6D activity and weaker D5D activity were observed in the OB group. A higher level of D9-16D activity as well as a higher level of D6D activity and a lower level of D5D activity was observed in the MS group. A logistic regression analysis showed that the low D5D activity and high D9-16D activity were predictive of the development of abdominal obesity from controls (odds ratio=0.39, p<0.05) and metabolic syndrome from abdominal obesity (odds ratio=2.44, p<0.05), respectively. In the multiple linear regression analysis, D5D activity positively correlated with the intake of eicosapentaenoic acid (EPA). In conclusion, the estimated D5D activity was a predictive factor for abdominal obesity and the estimated D9-16D activity was a predictive factor for developing metabolic syndrome from abdominal obesity in Japanese male subjects. Dietary intake of EPA would play an important role in preventing abdominal obesity and the development of metabolic syndrome.

  2. A 12-week aerobic exercise program reduces hepatic fat accumulation and insulin resistance in obese, Hispanic adolescents.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The rise in obesity-related morbidity in children and adolescents requires urgent prevention and treatment strategies. Currently, only limited data are available on the effects of exercise programs on insulin resistance, and visceral, hepatic, and intramyocellular fat accumulation. We hypothesized t...

  3. A 12 week aerobic exercise program improves fitness, hepatic insulin sensitivity and glucose metabolism in obese Hispanic adolescents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The rise in obesity related morbidity in children and adolescents requires urgent prevention and treatment strategies. Strictly controlled exercise programs might be useful tools to improve insulin sensitivity and glucose kinetics. Our objective was to test the hypothesis that a 12-wk aerobic exerci...

  4. Soy protein isolates prevent loss of bone quantity associated with obesity in rats through regulation of insulin signaling in osteoblasts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In both rodents and humans, excessive consumption of a typical Western diet high in saturated fats and cholesterol is known to result in disruption of energy metabolism and development of obesity and insulin resistance. However, how these high-fat, energy-dense diets affect bone development, morphol...

  5. Soy protein isolates prevent loss of bone quantity associated with obesity in rats through regulation of insulin signaling in osteoblasts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In both rodents and humans, excessive consumption of a typical Western diet high in saturated fats and cholesterol during postnatal life is known to result in disruption of energy metabolism, development of obesity and of insulin resistance. However, how these high fat, energy dense diets affect bon...

  6. Skeletal effects of obesity are prevented by a diet containing soy protein isolate via preservation of insulin signaling in bone

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In both rodents and humans, excessive consumption of diets high in saturated fat and cholesterol during postnatal life is known to result in global energy imbalance, obesity, and insulin resistance. However, the effects of such a "Western diet" (WD) on bone development and remodeling is poorly under...

  7. Ubc13 haploinsufficiency protects against age-related insulin resistance and high-fat diet-induced obesity

    PubMed Central

    Joo, Erina; Fukushima, Toru; Harada, Norio; Reed, John C.; Matsuzawa, Shu-ichi; Inagaki, Nobuya

    2016-01-01

    Obesity is associated with low-grade inflammation that leads to insulin resistance and type 2 diabetes via Toll-like Receptor (TLR) and TNF-family cytokine receptor (TNFR) signaling pathways. Ubc13 is an ubiquitin-conjugating enzyme responsible for non-canonical K63-linked polyubiquitination of TNF receptor-associated factor (TRAF)-family adapter proteins involved in TLR and TNFR pathways. However, the relationship between Ubc13 and metabolic disease remains unclear. In this study, we investigated the role of Ubc13 in insulin resistance and high-fat diet (HFD)-induced obesity. We compared wild-type (WT) and Ubc13 haploinsufficient (ubc13+/−) mice under normal diet (ND) and HFD, since homozygous knockout mice (ubc13−/−) are embryonic lethal. Male and female ubc13+/− mice were protected against age-related insulin resistance under ND and HFD compared to WT mice. Interestingly, only female ubc13+/− mice were protected against HFD-induced obesity and hepatic steatosis. Moreover, only female HFD-fed ubc13+/− mice showed lower expression of inflammatory cytokines that was secondary to reduction in weight gain not present in the other groups. In summary, our results indicate that suppression of Ubc13 activity may play a metabolic role independent of its inflammatory function. Thus, Ubc13 could represent a therapeutic target for insulin resistance, diet-induced obesity, and associated metabolic dysfunctions. PMID:27796312

  8. Short-Term Aerobic Exercise Training in Obese Humans with Type 2 Diabetes Mellitus Improves Whole-Body Insulin Sensitivity through Gains in Peripheral, not Hepatic Insulin Sensitivity

    PubMed Central

    Winnick, Jason J.; Sherman, W. Michael; Habash, Diane L.; Stout, Michael B.; Failla, Mark L.; Belury, Martha A.; Schuster, Dara P.

    2008-01-01

    Context: Short-term aerobic exercise training can improve whole-body insulin sensitivity in humans with type 2 diabetes mellitus; however, the contributions of peripheral and hepatic tissues to these improvements are not known. Objective: Our objective was to determine the effect of 7-d aerobic exercise training on peripheral and hepatic insulin sensitivity during isoglycemic/hyperinsulinemic clamp conditions. Design: Subjects were randomly assigned to one of two groups. The energy balance group consumed an isocaloric diet consisting of 50% carbohydrate, 30% fat, and 20% protein for 15 d. The energy balance plus exercise group consumed a similar diet over the 15 d and performed 50-min of treadmill walking at 70% of maximum oxygen consumption maximum during the second 7 d of the 15-d study period. Each subject underwent an initial isoglycemic/hyperinsulinemic clamp after 1-wk dietary control and a second clamp after completing the study. Setting: The study was performed at Ohio State University’s General Clinical Research Center. Participants: There were 18 obese, mildly diabetic humans included in the study. Intervention: Aerobic exercise training was performed for 7 d. Main Outcome Measures: Whole-body, peripheral, and hepatic insulin sensitivity were measured. Results: Exercise training did not have an impact on peripheral glucose uptake or endogenous glucose production during the basal state or low-dose insulin. Likewise, it did not alter endogenous glucose production during high-dose insulin. However, 1-wk of exercise training increased both whole-body (P < 0.05) and peripheral insulin sensitivity (P < 0.0001) during high-dose insulin. Conclusion: Improvements to whole body insulin sensitivity after short-term aerobic exercise training are due to gains in peripheral, not heptic insulin sensitivity. PMID:18073312

  9. Adherence to the Baltic Sea diet consumed in the Nordic countries is associated with lower abdominal obesity.

    PubMed

    Kanerva, Noora; Kaartinen, Niina E; Schwab, Ursula; Lahti-Koski, Marjaana; Männistö, Satu

    2013-02-14

    Due to differences in food cultures, dietary quality measures, such as the Mediterranean Diet Score, may not be easily adopted by other countries. Recently, the Baltic Sea Diet Pyramid was developed to illustrate healthy choices for the diet consumed in the Nordic countries. We assessed whether the Baltic Sea Diet Score (BSDS) based on the Pyramid is associated with a decreased risk of obesity and abdominal obesity. The population-based cross-sectional study included 4720 Finns (25-74 years) from the National FINRISK 2007 study. Diet was assessed using a validated FFQ. The score included Nordic fruits and berries, vegetables, cereals, ratio of PUFA:SFA and trans-fatty acids, low-fat milk, fish, red and processed meat, total fat (percentage of energy), and alcohol. Height, weight and waist circumference (WC) were measured and BMI values were calculated. In a multivariable model, men in the highest v. lowest BSDS quintile were more likely to have normal WC (OR 0·48, 95 % CI 0·29, 0·80). In women, this association was similar but not significant (OR 0·65, 95 % CI 0·39, 1·09). The association appeared to be stronger in younger age groups (men: OR 0·23, 95 % CI 0·08, 0·62; women: OR 0·17, 95 % CI 0·05, 0·58) compared with older age groups. Nordic cereals and alcohol were found to be the most important BSDS components related to WC. No association was observed between the BSDS and BMI. The present study suggests that combination of Nordic foods, especially cereals and moderate alcohol consumption, is likely to be inversely associated with abdominal obesity.

  10. Estimating Negative Effect of Abdominal Obesity on Mildly Decreased Kidney Function Using a Novel Index of Body-Fat Distribution

    PubMed Central

    2017-01-01

    Abdominal obesity is a major risk factor of chronic kidney disease (CKD). Conventional obesity-related indicators, included body mass index (BMI), waist circumference (WC), and conicity index (C-index), have some limitations. We examined the usefulness of trunk/body fat mass ratio (T/Br) to predict negative effect of abnormal fat distribution on excretory kidney function. We analyzed anthropometric, biochemical and densitometric data from a nation-wide, population-based, case-control study (the Korean National Health and Nutrition Examination Survey [KNHANES] IV and V). A total of 11,319 participants were divided into 2 groups according to estimated glomerular filtration rate (eGFR, mL·min-1·1.73 m-2) as follows: Group I (n = 7,980), eGFR ≥ 90 and ≤ 120; and group II (n = 3,339), eGFR ≥ 60 and < 90. Linear regression analysis revealed that T/Br was closely related to eGFR (β = −0.3173, P < 0.001), and the correlation remained significant after adjustment for age, gender, BMI, WC, C-index, systolic blood pressure (BP), hemoglobin, and smoking amount (β = −0.0987, P < 0.001). Logistic regression analysis showed that T/Br (odds ratio [OR] = 1.046; 95% confidence interval [CI] = 1.039–1.054) was significantly associated with early decline of kidney function, and adjustment for age, gender, BMI, C-index, systolic BP, hemoglobin, serum glucose level, high-density lipoprotein (HDL)-cholesterol, and smoking amount did not reduce the association (OR = 1.020; 95% CI = 1.007–1.033). T/Br is useful in estimating the negative impact of abdominal obesity on the kidney function. PMID:28244287

  11. Abdominal obesity explains the positive rural-urban gradient in the prevalence of the metabolic syndrome in Benin, West Africa.

    PubMed

    Ntandou, Gervais; Delisle, Hélène; Agueh, Victoire; Fayomi, Benjamin

    2009-03-01

    This cross-sectional study was designed to verify the hypothesis that there is a positive rural-urban gradient in the overall prevalence of the metabolic syndrome (MetS) and its components and that the differences are associated with socioeconomic status, a sedentary lifestyle, and poor diet quality. A sample of 541 Beninese adults apparently healthy was randomly selected from rural (n = 170), semi-urban (n = 171), and urban (n = 200) areas. The MetS was defined according to the International Diabetes Federation. Diet and physical activity were assessed with a 3-day recall. Socioeconomic and additional lifestyle information was obtained during personal interviews. A positive rural-urban gradient (rural to semi-urban to urban) was observed for the overall prevalence of the MetS (4.1%, 6.4%, and 11%, respectively; P = .035), which reflected that of abdominal obesity (28.2%, 41.5%, 52.5%; P < .001) but not for the other prominent features of the MetS, that is, high blood pressure (HBP; 24.1%, 21.6%, and 26.5%; P > .05) and reduced high-density lipoprotein cholesterol (HDL-C; 25.3%, 18.1%, 37.5%; P < .001). Diet quality and physical activity were higher in rural and semi-urban compared to urban subjects. Physical activity appeared protective for obesity, HBP, and low HDL-C. Micronutrient adequacy was an independent predictor of HDL-C and was associated with a lower likelihood of HBP. Socioeconomic status was positively associated with abdominal obesity only, which was more widespread in women than in men. This study shows that the nutrition transition is ongoing in Benin and suggests that cardiovascular disease risk could be reduced substantially by promoting physical activity and a more adequate diet.

  12. PER2 variants are associated with abdominal obesity, psycho-behavioral factors and attrition in the dietary treatment of obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose was to test for association between polymorphisms in the circadian clock-related gene PER2 and attrition in patients prone to withdrawal from a behavioral weight-reduction-program based on the Mediterranean Diet. 454 overweight/obese subjects (women= 380, men= 74), aged 20-65 years, who ...

  13. Relationships between changes in leptin and insulin resistance levels in obese individuals following weight loss.

    PubMed

    Wang, Tsu-Nai; Chang, Wen-Tsan; Chiu, Yu-Wen; Lee, Chun-Ying; Lin, Kun-Der; Cheng, Yu Yao; Su, Yi-Ju; Chung, Hsin-Fang; Huang, Meng-Chuan

    2013-08-01

    Obesity can augment insulin resistance (IR), leading to increased risk of diabetes and heart disease. Leptin, ghrelin, and various fatty acids present in the cell membrane may modulate IR. In this study, we aimed to investigate the impact of weight loss on IR, serum leptin/ghrelin levels, and erythrocyte fatty acids, and studied the associations between changes in these variables. A total of 35 obese (body mass index ≥ 27) adults participated in a weight loss program for 3 months. IR was assessed using homeostasis model assessment for insulin resistance (HOMA-IR). The obese participants had a mean weight loss of 5.6 ± 3.8 kg followed by a 16.7% and 23.3% reduction in HOMA-IR and leptin (p < 0.001) levels, and an 11.3% increase in ghrelin levels (p = 0.005). The level of erythrocyte saturates decreased by 2.8%, while the level of n-3 polyunsaturates increased by 16.8% (all p < 0.05). The changes in leptin levels (-5.63 vs. -1.57 ng/mL) were significantly different (p = 0.004) in those with improved IR (changes in HOMA-IR < 0) than those without improvement (changes in HOMA-IR ≥ 0), though there were no differences in the changes of ghrelin (p = 0.120) and erythrocyte fatty acids (all p > 0.05) levels. After adjusting for age, gender, changes in ghrelin, and body fat, we found a significant correlation between decreases in leptin and less risk of no improvement in HOMA-IR levels [odds ratio (OR) = 0.69, p = 0.039]. In conclusion, a moderate weight reduction in obese participants over a short period significantly improved IR. This weight reduction concomitantly decreased serum leptin, increased ghrelin, and elevated some erythrocyte unsaturates. Only leptin correlated independently with IR improvement upon multivariable logistic regression analysis, which indicates that leptin may play a role in the modulation of IR following weight loss.

  14. Insulin Receptor Signaling in the GnRH Neuron Plays a Role in the Abnormal GnRH Pulsatility of Obese Female Mice

    PubMed Central

    DiVall, Sara A.; Herrera, Danny; Sklar, Bonnie; Wu, Sheng; Wondisford, Fredric; Radovick, Sally; Wolfe, Andrew

    2015-01-01

    Infertility associated with obesity is characterized by abnormal hormone release from reproductive tissues in the hypothalamus, pituitary, and ovary. These tissues maintain insulin sensitivity upon peripheral insulin resistance. Insulin receptor signaling may play a role in the dysregulation of gonadotropin-releasing hormone (GnRH) secretion in obesity, but the interdependence of hormone secretion in the reproductive axis and the multi-hormone and tissue dysfunction in obesity hinders investigations of putative contributing factors to the disrupted GnRH secretion. To determine the role of GnRH insulin receptor signaling in the dysregulation of GnRH secretion in obesity, we created murine models of diet-induced obesity (DIO) with and without intact insulin signaling in the GnRH neuron. Obese control female mice were infertile with higher luteinizing hormone levels and higher GnRH pulse amplitude and total pulsatile secretion compared to lean control mice. In contrast, DIO mice with a GnRH specific knockout of insulin receptor had improved fertility, luteinizing hormone levels approaching lean mice, and GnRH pulse amplitude and total secretion similar to lean mice. Pituitary responsiveness was similar between genotypes. These results suggest that in the obese state, insulin receptor signaling in GnRH neurons increases GnRH pulsatile secretion and consequent LH secretion, contributing to reproductive dysfunction. PMID:25780937

  15. Association of free fatty acids with the insulin-resistant state but not with central obesity in individuals from Venezuela.

    PubMed

    Campos, Gilberto; Fernández, Virginia; Fernández, Erika; Molero, Emperatriz; Morales, Luz Marina; Raleigh, Xiomara; Connell, Lissette; Ryder, Elena

    2010-03-01

    Individuals with insulin resistance (IR) usually have upper body obesity phenotype, often accompanied by an increase in plasma free fatty acids (FFA). Since the Venezuelan population has a high frequency of IR and central obesity, the purpose of this work was to determine FFA levels in 47 Venezuelan individuals, men and women, 24-58 years old, and analyze their relationship with central obesity and parameters of carbohydrate and lipid metabolism. Basal concentrations of TG, total cholesterol, LDL-C, and HDL-C were measured, and FFA, glucose and insulin, at basal state and at different times after a glucose load. Eighteen individuals presented insulin resistance (HOMA-IR > 2.7) and 29 were non-insulin resistant (non-IR). Insulin resistant individuals (IR) had higher waist circumference, BMI and basal concentrations of FFA than the non-IR. No differences were observed in skin folds and other basal lipids studied. The increased FFA seemed to be related to the IR associated to BMI and not to central obesity, since the difference between IR and non-IR disappeared when they were matched for waist circumference. After a glucose load, FFA decreased in both groups, but remained significantly elevated in IR subjects. This effect disappeared after matching for BMI or waist circumference, inferring that it was independent of anthropometries. FFA were positively associated with HOMA-IR, glucose and TG levels; however, there was.no association with BMI or waist circumference. These findings, and the lack of elements to support the presence of hepatic IR, common to increased visceral lipolysis, might suggest that the IR present in the obese individuals studied, might be due to an increase in subcutaneous fat.

  16. Glucose and insulin modify thrombospondin 1 expression and secretion in primary adipocytes from diet-induced obese rats.

    PubMed

    Garcia-Diaz, Diego F; Arellano, Arianna V; Milagro, Fermin I; Moreno-Aliaga, Maria Jesus; Portillo, Maria Puy; Martinez, J Alfredo; Campion, Javier

    2011-09-01

    Thrombospondin 1 (TSP-1), an antiangiogenic factor and transforming growth factor (TGF)-β activity regulator, has been recently recognized as an adipokine that correlates with obesity, inflammation and insulin resistance processes. In the present study, epididymal adipocytes of rats that were fed a chow or a high-fat diet (HFD) for 50 days were isolated and incubated (24-72 h) in low (5.6 mM) or high (HG; 25 mM) glucose, in the presence or absence of 1.6 nM insulin. Rats fed the HF diet showed an established obesity state. Serum TSP-1 levels and TSP-1 mRNA basal expression of adipocytes from HFD rats were higher than those from controls. Adipocytes from HFD animals presented an insulin resistance state, as suggested by the lower insulin-stimulated glucose uptake as compared to controls. TSP-1 expression in culture was higher in adipocytes from obese animals at 24 h, but when the adipocytes were treated with HG, these expression levels dropped dramatically. Later at 72 h, TSP-1 expression was lower in adipocytes from HFD rats, and no effects of the other treatments were observed. Surprisingly, the secretion levels of this protein at 72 h were increased significantly by the HG treatment in both types of adipocytes, although they were even higher in adipocytes from obese animals. Finally, cell viability was significantly reduced by HG treatment in both types of adipocytes. In summary, TSP-1 expression/secretion was modulated in an in vitro model of insulin-resistant adipocytes. The difference between expression and secretion patterns suggests a posttranscriptional regulation. The present study confirms that TPS-1 is closely associated with obesity-related mechanisms.

  17. Effects of Aerobic Exercise on Serum Retinol Binding Protein4, Insulin Resistance and Blood Lipids in Obese Women

    PubMed Central

    TAGHIAN, Farzaneh; ZOLFAGHARI, Maryam; HEDAYATI, Mehdi

    2014-01-01

    Abstract Background Retinol binding protein4 (RBP4) is a type of adipokine which transports vitamin A to serum. RBP4 could be a bridge between obesity and insulin resistance. This study aimed to investigate the effects of aerobic exercises on RBP4 serum’s concentration and metabolic syndrome risk factors in obese women. Methods Twenty obese women with body max index 35.81±3.67Kg/m2, fat percentage 43.98±4.02, and waist to hip ratio 1.03±0.05 were included and were randomly assigned to experimental and control groups. The experimental group received aerobic exercises for a period of 12 weeks each three sessions on treadmill workout. The treadmill speed were based on a 60-65 and 80-85 maximal heart rate percentage and duration of 15-20 and 45-50 minutes, at the beginning and the end of exercise, respectively. Body composition, serum glucose, insulin, TG, LDL-C, HDL-C, total cholesterol, and RBP4, were measured in both groups before and after the treatment by ELISA method. Insulin resistance was measured by HOMA-IR. To compare within group differences and between group comparisons t-correlated and t-independent tests were used, respectively. Results After 12 week aerobic exercises; weight, fat percentage, WHR, and BMI in the experimental group was significantly decreased (P<0.05). RBP4, insulin, insulin resistance, TG and HDL-C had significant differences between two groups. The cholesterol level, LDL-C and glucose did not have any significant changes. Conclusion The aerobic exercises can decrease body composition, insulin resistance, TG, and RBP4, so it can be beneficial for obese women’s health, because it. PMID:26060767

  18. Modulatory role of D-chiro-inositol (DCI) on LH and insulin secretion in obese PCOS patients.

    PubMed

    Genazzani, Alessandro D; Santagni, Susanna; Rattighieri, Erika; Chierchia, Elisa; Despini, Giulia; Marini, Giulia; Prati, Alessia; Simoncini, Tommaso

    2014-06-01

    Polycystic ovary syndrome (PCOS) is a common endocrine condition that affects fertility through oligo-ovulation, hyperandrogenism and polycystic morphology of the ovaries. Since it has been demonstrated a high incidence of insulin resistance in PCOS patients, our study aimed to evaluate the efficacy of the integrative treatment with D-chiro-inositol (DCI) (500 mg die, per os, for 12 weeks) on hormonal parameters and insulin sensitivity in a group of overweight/obese PCOS patients (body mass index; BMI > 26). After the treatment, interval several endocrine parameters improved (luteinizing hormone [LH], LH/follicle stimulating hormone [FSH], androstenedione and insulin), insulin response to oral glucose tolerance test reported the significant improvement of insulin sensitivity as well as the gonadotropin-releasing hormone (GnRH)-induced (10 µg, in bolus) LH response. BMI decreased, though no lifestyle modification was requested. When data were analyzed according to the presence or absence of first-grade diabetic relatives, PCOS patients with diabetic relatives showed greater improvement after DCI administration. In conclusion DCI administration is effective in restoring better insulin sensitivity and an improved hormonal pattern in obese hyperinsulinemic PCOS patients, in particular, in hyperinsulinemic PCOS patients who have diabetic relatives.

  19. Beneficial Effects of Canagliflozin in Combination with Pioglitazone on Insulin Sensitivity in Rodent Models of Obese Type 2 Diabetes

    PubMed Central

    Watanabe, Yoshinori; Nakayama, Keiko; Taniuchi, Nobuhiko; Horai, Yasushi; Kuriyama, Chiaki; Ueta, Kiichiro; Arakawa, Kenji; Senbonmatsu, Takaaki; Shiotani, Masaharu

    2015-01-01

    Background Despite its insulin sensitizing effects, pioglitazone may induce weight gain leading to an increased risk of development of insulin resistance. A novel sodium glucose co-transporter 2 (SGLT2) inhibitor, canagliflozin, provides not only glycemic control but also body weight reduction through an insulin-independent mechanism. The aim of this study was to investigate the combined effects of these agents on body weight control and insulin sensitivity. Methods Effects of combination therapy with canagliflozin and pioglitazone were evaluated in established diabetic KK-Ay mice and prediabetic Zucker diabetic fatty (ZDF) rats. Results In the KK-Ay mice, the combination therapy further improved glycemic control compared with canagliflozin or pioglitazone monotherapy. Furthermore, the combination significantly attenuated body weight and fat gain induced by pioglitazone and improved hyperinsulinemia. In the ZDF rats, early intervention with pioglitazone monotherapy almost completely prevented the progressive development of hyperglycemia, and no further improvement was observed by add-on treatment with canagliflozin. However, the combination significantly reduced pioglitazone-induced weight gain and adiposity and improved the Matsuda index, suggesting improved whole-body insulin sensitivity. Conclusions Our study indicates that combination therapy with canagliflozin and pioglitazone improves insulin sensitivity partly by preventing glucotoxicity and, at least partly, by attenuating pioglitazone-induced body weight gain in two different obese diabetic animal models. This combination therapy may prove to be a valuable option for the treatment and prevention of obese type 2 diabetes. PMID:25615826

  20. Early-onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma-like disease in mice

    PubMed Central

    Dinger, Katharina; Kasper, Philipp; Hucklenbruch-Rother, Eva; Vohlen, Christina; Jobst, Eva; Janoschek, Ruth; Bae-Gartz, Inga; van Koningsbruggen-Rietschel, Silke; Plank, Christian; Dötsch, Jörg; Alejandre Alcázar, Miguel Angel

    2016-01-01

    Childhood obesity is a risk factor for asthma, but the molecular mechanisms linking both remain elusive. Since obesity leads to chronic low-grade inflammation and affects metabolic signaling we hypothesized that postnatal hyperalimentation (pHA) induced by maternal high-fat-diet during lactation leads to early-onset obesity and dysregulates pulmonary adipocytokine/insulin signaling, resulting in metabolic programming of asthma-like disease in adult mice. Offspring with pHA showed at postnatal day 21 (P21): (1) early-onset obesity, greater fat-mass, increased expression of IL-1β, IL-23, and Tnf-α, greater serum leptin and reduced glucose tolerance than Control (Ctrl); (2) less STAT3/AMPKα-activation, greater SOCS3 expression and reduced AKT/GSK3β-activation in the lung, indicative of leptin resistance and insulin signaling, respectively; (3) increased lung mRNA of IL-6, IL-13, IL-17A and Tnf-α. At P70 body weight, fat-mass, and cytokine mRNA expression were similar in the pHA and Ctrl, but serum leptin and IL-6 were greater, and insulin signaling and glucose tolerance impaired. Peribronchial elastic fiber content, bronchial smooth muscle layer, and deposition of connective tissue were not different after pHA. Despite unaltered bronchial structure mice after pHA exhibited significantly increased airway reactivity. Our study does not only demonstrate that early-onset obesity transiently activates pulmonary adipocytokine/insulin signaling and induces airway hyperreactivity in mice, but also provides new insights into metabolic programming of childhood obesity-related asthma. PMID:27087690

  1. CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of macrophage polarization in adipose tissues

    SciTech Connect

    Fujii, Masakazu; Inoguchi, Toyoshi; Batchuluun, Battsetseg; Sugiyama, Naonobu; Kobayashi, Kunihisa; Sonoda, Noriyuki; Takayanagi, Ryoichi

    2013-08-16

    Highlights: •CTLA-4Ig completely alleviates HFD-induced insulin resistance. •CTLA-4Ig reduces epididymal and subcutaneous fat tissue weight and adipocyte size. •CTLA-4Ig alters ATM polarization from inflammatory M1 to anti-inflammatory M2. •CTLA-4Ig may lead to a novel anti-obesity/inflammation/insulin resistance agent. •We identified the mechanism of the novel favorable effects of CTLA-4lg. -- Abstract: It has been established that obesity alters the metabolic and endocrine function of adipose tissue and, together with accumulation of adipose tissue macrophages, contributes to insulin resistance. Although numerous studies have reported that shifting the polarization of macrophages from M1 to M2 can alleviate adipose tissue inflammation, manipulation of macrophage polarization has not been considered as a specific therapy. Here, we determined whether cytotoxic T-lymphocyte-associated antigen-4IgG1 (CTLA-4Ig) can ameliorate insulin resistance by induction of macrophages from proinflammatory M1 to anti-inflammatory M2 polarization in the adipose tissues of high fat diet-induced insulin-resistant mice. CTLA4-Ig treatment prevented insulin resistance by changing gene expression to M2 polarization, which increased the levels of arginase 1. Furthermore, flow cytometric analysis confirmed the alteration of polarization from CD11c (M1)- to CD206 (M2)-positive cells. Concomitantly, CTLA-4Ig treatment resulted in weight reductions of epididymal and subcutaneous adipose tissues, which may be closely related to overexpression of apoptosis inhibitors in macrophages. Moreover, proinflammatory cytokine and chemokine levels decreased significantly. In contrast, CCAAT enhancer binding protein α, peroxisome proliferator-activated receptor γ, and adiponectin expression increased significantly in subcutaneous adipose tissue. This novel mechanism of CTLA-4lg immunotherapy may lead to an ideal anti-obesity/inflammation/insulin resistance agent.

  2. Pharmacokinetics and Pharmacodynamics of High-Dose Human Regular U-500 Insulin Versus Human Regular U-100 Insulin in Healthy Obese Subjects

    PubMed Central

    de la Peña, Amparo; Riddle, Matthew; Morrow, Linda A.; Jiang, Honghua H.; Linnebjerg, Helle; Scott, Adam; Win, Khin M.; Hompesch, Marcus; Mace, Kenneth F.; Jacobson, Jennie G.; Jackson, Jeffrey A.

    2011-01-01

    OBJECTIVE Human regular U-500 (U-500R) insulin (500 units/mL) is increasingly being used clinically, yet its pharmacokinetics (PK) and pharmacodynamics (PD) have not been well studied. Therefore, we compared PK and PD of clinically relevant doses of U-500R with the same doses of human regular U-100 (U-100R) insulin (100 units/mL). RESEARCH DESIGN AND METHODS This was a single-site, randomized, double-blind, crossover euglycemic clamp study. Single subcutaneous injections of 50- and 100-unit doses of U-500R and U-100R were administered to 24 healthy obese subjects. RESULTS Both overall insulin exposure (area under the serum insulin concentration versus time curve from zero to return to baseline [AUC0-t’]) and overall effect (total glucose infused during a clamp) were similar between formulations at both 50- and 100-unit doses (90% [CI] of ratios contained within [0.80, 1.25]). However, peak concentration and effect were significantly lower for U-500R at both doses (P < 0.05). Both formulations produced relatively long durations of action (18.3 to 21.5 h). Time-to-peak concentration and time to maximum effect were significantly longer for U-500R than U-100R at the 100-unit dose (P < 0.05). Time variables reflective of duration of action (late tRmax50, tRlast) were prolonged for U-500R versus U-100R at both doses (P < 0.05). CONCLUSIONS Overall exposure to and action of U-500R insulin after subcutaneous injection were no different from those of U-100R insulin. For U-500R, peaks of concentration and action profiles were blunted and the effect after the peak was prolonged. These findings may help guide therapy with U-500R insulin for highly insulin-resistant patients with diabetes. PMID:21994429

  3. Ginkgo biloba Extract Improves Insulin Signaling and Attenuates Inflammation in Retroperitoneal Adipose Tissue Depot of Obese Rats

    PubMed Central

    Hirata, Bruna Kelly Sousa; Banin, Renata Mancini; Dornellas, Ana Paula Segantine; de Andrade, Iracema Senna; Zemdegs, Juliane Costa Silva; Caperuto, Luciana Chagas; Oyama, Lila Missae; Ribeiro, Eliane Beraldi; Telles, Monica Marques

    2015-01-01

    Due to the high incidence and severity of obesity and its related disorders, it is highly desirable to develop new strategies to treat or even to prevent its development. We have previously described that Ginkgo biloba extract (GbE) improved insulin resistance and reduced body weight gain of obese rats. In the present study we aimed to evaluate the effect of GbE on both inflammatory cascade and insulin signaling in retroperitoneal fat depot of diet-induced obese rats. Rats were fed with high fat diet for 2 months and thereafter treated for 14 days with 500 mg/kg of GbE. Rats were then euthanized and samples from retroperitoneal fat depot were used for western blotting, RT-PCR, and ELISA experiments. The GbE treatment promoted a significant reduction on both food/energy intake and body weight gain in comparison to the nontreated obese rats. In addition, a significant increase of both Adipo R1 and IL-10 gene expressions and IR and Akt phosphorylation was also observed, while NF-κB p65 phosphorylation and TNF-α levels were significantly reduced. Our data suggest that GbE might have potential as a therapy to treat obesity-related metabolic diseases, with special interest to treat obese subjects resistant to adhere to a nutritional education program. PMID:25960614

  4. Skeletal muscle peroxisome proliferator- activated receptor-gamma expression in obesity and non- insulin-dependent diabetes mellitus.

    PubMed Central

    Kruszynska, Y T; Mukherjee, R; Jow, L; Dana, S; Paterniti, J R; Olefsky, J M

    1998-01-01

    The two isoforms of peroxisome proliferator-activated receptor-gamma (PPARgamma1 and PPARgamma2), are ligand-activated transcription factors that are the intracellular targets of a new class of insulin sensitizing agents, the thiazolidinediones. The observation that thiazolidinediones enhance skeletal muscle insulin sensitivity in obesity and in patients with non-insulin-dependent diabetes mellitus (NIDDM), by activating PPARgamma, and possibly by inducing its expression, suggests that PPARgamma expression in skeletal muscle plays a key role in determining tissue sensitivity to insulin, and that PPARgamma expression may be decreased in insulin resistant subjects. We used a sensitive ribonuclease protection assay, that permits simultaneous measurement of the two isoforms, to examine the effects of obesity and NIDDM, and the effects of insulin, on skeletal muscle levels of PPARgamma1 and PPARgamma2 mRNA. We studied seven patients with NIDDM (body mass index, 32+/-1 kg/m2), seven lean (24+/-1 kg/m2), and six obese (36+/-1 kg/m2) normal subjects. Biopsies from the vastus lateralis muscle were taken before and after a 5-h hyperinsulinemic (80 mU/m2 per minute) euglycemic clamp. The obese controls and NIDDM patients were insulin resistant with glucose disposal rates during the last 30 min of the clamp that were 67 and 31%, respectively, of those found in the lean controls. PPARgamma1, but not PPARgamma2 mRNA was detected in skeletal muscle at 10-15% of the level found in adipose tissue. No difference was found in PPARgamma1 levels between the three groups, and there was no change in PPARgamma1 levels after 5 h of hyperinsulinemia. In obese subjects, PPARgamma1 correlated with clamp glucose disposal rates (r = 0.92, P < 0.01). In the lean and NIDDM patients, muscle PPARgamma1 levels correlated with percentage body fat (r = 0.76 and r = 0.82, respectively, both P < 0.05) but not with body mass index. In conclusion: (a) skeletal muscle PPARgamma1 expression does not differ

  5. Prevalence of Abdominal Obesity in Spanish Children and Adolescents. Do We Need Waist Circumference Measurements in Pediatric Practice?

    PubMed Central

    Schröder, Helmut; Ribas, Lourdes; Koebnick, Corinna; Funtikova, Anna; Gomez, Santiago F.; Fíto, Montserat; Perez-Rodrigo, Carmen; Serra-Majem, Lluis

    2014-01-01

    Background Evidence indicates that central adiposity has increased to a higher degree than general adiposity in children and adolescents in recent decades. However, waist circumference is not a routine measurement in clinical practice. Objective This study aimed to determine the prevalence of abdominal obesity based on waist circumferences (WC) and waist to height ratio (WHtR) in Spanish children and adolescents aged 6 to 17 years. Further, the prevalence of abdominal obesity (AO) among normal and overweight individuals was analyzed. Design Data were obtained from a study conducted from 1998 to 2000 in a representative national sample of 1521 children and adolescents aged 6 to 17 years (50.0% female) in Spain. WC and WHtR measurements were obtained in addition to BMI. AO was defined as WHtR ≥0.50 (WHtR-AO), sex and age specific WC≥90th percentile (WC-AO1), and sex and age specific WC cut-off values associated with high trunk fat measured by by dual-energy X-ray absorptiometry (WC-AO2). Results IOTF- based overweight and obsity prevalence was 21.5% and 6.6% in children and 17.4% and 5.2% in adolescents, respectively. Abdominal obesity (AO) was defined as WHtR≥0.50 (WHtR-AO), sex- and age-specific WC≥90th percentile (WC-AO1), and sex- and age-specific WC cut-off values associated with high trunk fat measured by dual-energy X-ray absorptiometry (WC-AO2). The respective prevalence of WHtR-AO, WC-AO1, and WC-AO2 was 21.3% (24.6% boys; 17.9% girls), 9.4% (9.1% boys; 9.7% girls), and 26.8% (30.6% boys;22.9% girls) in children and 14.3% (20.0% boys; 8.7% girls), 9.6% (9.8% boys; 9.5% girls), and 21.1% (28.8% boys; 13.7% girls) in adolescents. Conclusion The prevalence of AO in Spanish children and adolescents is of concern. The high proportion of AO observed in young patients who are normal weight or overweight indicates a need to include waist circumference measurements in routine clinical practice. PMID:24475305

  6. Diminished anabolic signaling response to insulin induced by intramuscular lipid accumulation is associated with inflammation in aging but not obesity.

    PubMed

    Rivas, Donato A; McDonald, Devin J; Rice, Nicholas P; Haran, Prashanth H; Dolnikowski, Gregory G; Fielding, Roger A

    2016-04-01

    The loss of skeletal muscle mass is observed in many pathophysiological conditions, including aging and obesity. The loss of muscle mass and function with aging is defined as sarcopenia and is characterized by a mismatch between skeletal muscle protein synthesis and breakdown. Characteristic metabolic features of both aging and obesity are increases in intramyocellular lipid (IMCL) content in muscle. IMCL accumulation may play a mechanistic role in the development of anabolic resistance and the progression of muscle atrophy in aging and obesity. In the present study, aged and high-fat fed mice were used to determine mechanisms leading to muscle loss. We hypothesized the accumulation of bioactive lipids in skeletal muscle, such as ceramide or diacylglycerols, leads to insulin resistance with aging and obesity and the inability to activate protein synthesis, contributing to skeletal muscle loss. We report a positive association between bioactive lipid accumulation and the loss of lean mass and muscle strength. Obese and aged animals had significantly higher storage of ceramide and diacylglycerol compared with young. Furthermore, there was an attenuated insulin response in components of the mTOR anabolic signaling pathway. We also observed differential increases in the expression of inflammatory cytokines and the phosphorylation of IκBα with aging and obesity. These data challenge the accepted role of increased inflammation in obesity-induced insulin resistance in skeletal muscle. Furthermore, we have now established IκBα with a novel function in aging-associated muscle loss that may be independent of its previously understood role as an NF-κB inhibitor.

  7. Obesity and Insulin Resistance Are the Central Issues in Prevention of and Care for Comorbidities

    PubMed Central

    Govers, Elisabeth

    2015-01-01

    For a long time the assumption has been that, although weight reduction was necessary and desirable, comorbidities were far more important and needed treatment even if weight loss was not a treatment goal, preferably with medication. This controversy leads to postponement of treatment, and later on causes very intensive medical treatment, thus, raising the health care costs to unacceptable levels, leading to the medicalization of individuals, and a declining of the responsibility of patients for their health, leaving the question of when to regard their own weight as a problem that should be dealt with up to individuals. The central problem is insulin resistance, which leads to a cascade of health problems. This condition should be diagnosed in primary practice and obesity clinics to ensure a better, tailor-made treatment for patients. Treatment should start at the earliest stage possible, when comorbidities are still reversible and includes a personalized dietary advice and counseling, preferably by a dietitian, to tackle insulin resistance. An exercise program is part of the treatment. PMID:27417770

  8. Insulin Resistance and Obesity Affect Lipid Profile in the Salivary Glands

    PubMed Central

    Matczuk, Jan; Zalewska, Anna; Łukaszuk, Bartłomiej; Knaś, Małgorzata; Maciejczyk, Mateusz; Garbowska, Marta; Ziembicka, Dominika M.; Waszkiel, Danuta; Chabowski, Adrian; Żendzian-Piotrowska, Małgorzata

    2016-01-01

    In today's world wrong nutritional habits together with a low level of physical activity have given rise to the development of obesity and its comorbidity, insulin resistance. More specifically, many researches indicate that lipids are vitally involved in the onset of a peripheral tissue (e.g., skeletal muscle, heart, and liver) insulin resistance. Moreover, it seems that diabetes can also induce changes in respect of lipid composition of both the salivary glands and saliva. However, judging by the number of research articles, the salivary glands lipid profile still has not been sufficiently explored. In the current study we aim to assess the changes in the main lipid fractions, namely, triacylglycerols, phospholipids, free fatty acids, and diacylglycerols, in the parotid and the submandibular salivary glands of rats exposed to a 5-week high fat diet regimen. We observed that the high caloric fat diet caused a significant change in the salivary glands lipid composition, especially with respect to PH and TG, but not DAG or FFAs, classes. The observed reduction in PH concentration is an interesting phenomenon frequently signifying the atrophy and malfunctions in the saliva secreting organs. On the other hand, the increased accumulation of TG in the glands may be an important clinical manifestation of metabolic syndrome and type 2 diabetes mellitus. PMID:27471733

  9. Obesity and Insulin Resistance Are the Central Issues in Prevention of and Care for Comorbidities.

    PubMed

    Govers, Elisabeth

    2015-06-04

    For a long time the assumption has been that, although weight reduction was necessary and desirable, comorbidities were far more important and needed treatment even if weight loss was not a treatment goal, preferably with medication. This controversy leads to postponement of treatment, and later on causes very intensive medical treatment, thus, raising the health care costs to unacceptable levels, leading to the medicalization of individuals, and a declining of the responsibility of patients for their health, leaving the question of when to regard their own weight as a problem that should be dealt with up to individuals. The central problem is insulin resistance, which leads to a cascade of health problems. This condition should be diagnosed in primary practice and obesity clinics to ensure a better, tailor-made treatment for patients. Treatment should start at the earliest stage possible, when comorbidities are still reversible and includes a personalized dietary advice and counseling, preferably by a dietitian, to tackle insulin resistance. An exercise program is part of the treatment.

  10. Brown adipose tissue activity as a target for the treatment of obesity/insulin resistance

    PubMed Central

    Poher, Anne-Laure; Altirriba, Jordi; Veyrat-Durebex, Christelle; Rohner-Jeanrenaud, Françoise

    2015-01-01

    Presence of brown adipose tissue (BAT), characterized by the expression of the thermogenic uncoupling protein 1 (UCP1), has recently been described in adult humans. UCP1 is expressed in classical brown adipocytes, as well as in “beige cells” in white adipose tissue (WAT). The thermogenic activity of BAT is mainly controlled by the sympathetic nervous system. Endocrine factors, such as fibroblast growth factor 21 (FGF21) and bone morphogenic protein factor-9 (BMP-9), predominantly produced in the liver, were shown to lead to activation of BAT thermogenesis, as well as to “browning” of WAT. This was also observed in response to irisin, a hormone secreted by skeletal muscles. Different approaches were used to delineate the impact of UCP1 on insulin sensitivity. When studied under thermoneutral conditions, UCP1 knockout mice exhibited markedly increased metabolic efficiency due to impaired thermogenesis. The impact of UCP1 deletion on insulin sensitivity in these mice was not reported. Conversely, several studies in both rodents and humans have shown that BAT activation (by cold exposure, β3-agonist treatment, transplantation and others) improves glucose tolerance and insulin sensitivity. Interestingly, similar results were obtained by adipose tissue-specific overexpression of PR-domain-containing 16 (PRDM16) or BMP4 in mice. The mediators of such beneficial effects seem to include FGF21, interleukin-6, BMP8B and prostaglandin D2 synthase. Interestingly, some of these molecules can be secreted by BAT itself, indicating the occurrence of autocrine effects. Stimulation of BAT activity and/or recruitment of UCP1-positive cells are therefore relevant targets for the treatment of obesity/type 2 diabetes in humans. PMID:25688211

  11. N-stearoylethanolamine restores pancreas lipid composition in obesity-induced insulin resistant rats.

    PubMed

    Onopchenko, Oleksandra V; Kosiakova, Galina V; Oz, Murat; Klimashevsky, Vitaliy M; Gula, Nadiya M

    2015-01-01

    This study investigates the protective effect of N-stearoylethanolamine (NSE), a bioactive N-acylethanolamine , on the lipid profile distribution in the pancreas of obesity-induced insulin resistant (IR) rats fed with prolonged high fat diet (58% of fat for 6 months). The phospholipid composition was determined using 2D thin-layer chromatography. The level of individual phospholipids was estimated by measuring inorganic phosphorus content. The fatty acid (FA) composition and cholesterol level were investigated by gas-liquid chromatography. Compared to controls, plasma levels of triglycerides and insulin were significantly increased in IR rats. The pancreas lipid composition indicated a significant reduction of the free cholesterol level and some phospholipids such as phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn), phosphatidylinositol (PtdIns), phosphatidylserine (PtdSer) compared to controls. Moreover, the FA composition of pancreas showed a significant redistribution of the main FA (18:1n-9, 18:2n-6, 18:3n-6 and 20:4n-6) levels between phospholipid, free FA, triglyceride fractions under IR conditions that was accompanied by a change in the estimated activities of Δ9-, Δ6-, Δ5-desaturase. Administration of N-stearoylethanolamine (NSE, 50 mg/kg daily per os for 2 weeks) IR rats triggered an increase in the content of free cholesterol, PtdCho and normalization of PtdEtn, PtdSer level. Furthermore, the NSE modulated the activity of desaturases, thus influenced FA composition and restored the FA ratios in the lipid fractions. These NSE-induced changes were associated with a normalization of plasma triglyceride content, considerable decrease of insulin and index HOMA-IR level in rats under IR conditions.

  12. An amino acid mixture improves glucose tolerance and lowers insulin resistance in the obese Zucker rat.

    PubMed

    Bernard, Jeffrey R; Liao, Yi-Hung; Ding, Zhenping; Hara, Daisuke; Kleinert, Maximilian; Nelson, Jeffrey L; Ivy, John L

    2013-07-01

    The purpose of this investigation was to test an amino acid mixture on glucose tolerance in obese Zucker rats [experiment (Exp)-1] and determine whether differences in blood glucose were associated with alterations in muscle glucose uptake [experiment (Exp)-2]. Exp-1 rats were gavaged with either carbohydrate (OB-CHO), carbohydrate plus amino acid mixture (OB-AA-1), carbohydrate plus amino acid mixture with increased leucine concentration (OB-AA-2) or water (OB-PLA). The glucose response in OB-AA-1 and OB-AA-2 were similar, and both were lower compared to OB-CHO. This effect of the amino acid mixtures did not appear to be solely attributable to an increase in plasma insulin. Rats in Exp-2 were gavaged with carbohydrate (OB-CHO), carbohydrate plus amino acid mixture (OB-AA-1) or water (OB-PLA). Lean Zuckers were gavaged with carbohydrate (LN-CHO). Fifteen minutes after gavage, a radiolabeled glucose analog was infused through a catheter previously implanted in the right jugular vein. Blood glucose was significantly lower in OB-AA-1 compared to OB-CHO while the insulin responses were similar. Glucose uptake was greater in OB-AA-1 compared with OB-CHO, and similar to that in LN-CHO in red gastrocnemius muscle (5.15 ± 0.29, 3.8 ± 0.27, 5.18 ± 0.34 µmol/100 g/min, respectively). Western blot analysis showed that Akt substrate of 160 kDa (AS160) phosphorylation was enhanced for OB-AA-1 and LN-CHO compared to OB-CHO. These findings suggest that an amino acid mixture improves glucose tolerance in an insulin resistant model and that these improvements are associated with an increase in skeletal muscle glucose uptake possibly due to improved intracellular signaling.

  13. Zingiber mioga reduces weight gain, insulin resistance and hepatic gluconeogenesis in diet-induced obese mice

    PubMed Central

    LEE, DA-HYE; AHN, JIYUN; JANG, YOUNG JIN; HA, TAE-YOUL; JUNG, CHANG HWA

    2016-01-01

    Zingiber mioga is a perennial herb belonging to the ginger family (Zingiberaceae) that is used medicinally to treat cough and rheumatism in China and consumed throughout Japan. The aim of the present study was to investigate the anti-obesity effects of Z. mioga following extraction with distilled water or 70% ethanol. In 3T3-L1 preadipocyte cells, Z. mioga water extract (ZMW) markedly inhibited adipogenesis, whereas the ethanol extract had no effect. In addition, we conducted ZMW feeding experiments (0.25 or 0.5% ZMW) in high-fat diet (HFD)-fed mice to examine the anti-obesity effects of Z. mioga in vivo. Body weight and serum triglyceride and cholesterol levels significantly decreased in the HFD + ZMW 0.5% group. Notably, ZMW decreased liver weight but not adipose tissue weight. Furthermore, insulin resistance and hepatic mRNA expression of gluconeogenic genes, such as phosphoenolpyruvate carboxykinase and G6Pase, were improved in the HFD + ZMW 0.5% group. Furthermore, ZMW treatment decreased hepatic lipogenic gene expression; however, it did not alter adipogenesis in fat tissue, suggesting that ZMW inhibits hepatosteatosis through the suppression of lipogenesis. ZMW improved HFD-induced hepatic inflammation. Collectively, the present findings suggest that ZMW may serve as a new and promising strategy for the treatment of hepatosteatosis. PMID:27347064

  14. Gut commensal Bacteroides acidifaciens prevents obesity and improves insulin sensitivity in mice.

    PubMed

    Yang, J-Y; Lee, Y-S; Kim, Y; Lee, S-H; Ryu, S; Fukuda, S; Hase, K; Yang, C-S; Lim, H S; Kim, M-S; Kim, H-M; Ahn, S-H; Kwon, B-E; Ko, H-J; Kweon, M-N

    2017-01-01

    In humans, the composition of gut commensal bacteria is closely correlated with obesity. The bacteria modulate metabolites and influence host immunity. In this study, we attempted to determine whether there is a direct correlation between specific commensal bacteria and host metabolism. As mice aged, we found significantly reduced body weight and fat mass in Atg7(ΔCD11c) mice when compared with Atg7(f/f) mice. When mice shared commensal bacteria by co-housing or feces transfer experiments, body weight and fat mass were similar in both mouse groups. By pyrosequencing analysis, Bacteroides acidifaciens (BA) was significantly increased in feces of Atg7(ΔCD11c) mice compared with those of control Atg7(f/f) mice. Wild-type C57BL/6 (B6) mice fed with BA were significantly more likely to gain less weight and fat mass than mice fed with PBS. Of note, the expression level of peroxisome proliferator-activated receptor alpha (PPARα) was consistently increased in the adipose tissues of Atg7(ΔCD11c) mice, B6 mice transferred with fecal microbiota of Atg7(ΔCD11c) mice, and BA-fed B6 mice. Furthermore, B6 mice fed with BA showed elevated insulin levels in serum, accompanied by increased serum glucagon-like peptide-1 and decreased intestinal dipeptidyl peptidase-4. These finding suggest that BA may have potential for treatment of metabolic diseases such as diabetes and obesity.

  15. Dipeptidyl peptidase 4 inhibitor improves brain insulin sensitivity, but fails to prevent cognitive impairment in orchiectomy obese rats.

    PubMed

    Pintana, Hiranya; Pongkan, Wanpitak; Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2015-08-01

    It is unclear whether the dipeptidyl peptidase 4 (DPP4) inhibitor can counteract brain insulin resistance, brain mitochondrial dysfunction, impairment of hippocampal synaptic plasticity and cognitive decline in testosterone-deprived obese rats. We hypothesized that DPP4 inhibitor vildagliptin improves cognitive function in testosterone-deprived obese rats by restoring brain insulin sensitivity, brain mitochondrial function and hippocampal synaptic plasticity. Thirty male Wistar rats received either a sham-operated (S, n=6) or bilateral orchiectomy (ORX, n=24). ORX rats were divided into two groups and fed with either a normal diet (ND (NDO)) or a high-fat diet (HFO) for 12 weeks. Then, ORX rats in each dietary group were divided into two subgroups (n=6/subgroup) to receive either a vehicle or vildagliptin (3 mg/kg per day, p.o.) for 4 weeks. After treatment, cognitive function, metabolic parameters, brain insulin sensitivity, hippocampal synaptic plasticity and brain mitochondrial function were determined in each rat. We found that HFO rats exhibited peripheral and brain insulin resistance, brain mitochondrial dysfunction, impaired hippocampal synaptic plasticity and cognitive decline. NDO rats did not develop peripheral and brain insulin resistance. However, impaired hippocampal synaptic plasticity and cognitive decline occurred. Vildagliptin significantly improved peripheral insulin sensitivity, restored brain insulin sensitivity and decreased brain mitochondrial reactive oxygen species production in HFO rats. However, vildagliptin did not restore hippocampal synaptic plasticity and cognitive function in both NDO and HFO rats. These findings suggest that vildagliptin could not counteract the impairment of hippocampal synaptic plasticity and cognitive decline in testosterone-deprived subjects, despite its effects on improved peripheral and brain insulin sensitivity as well as brain mitochondrial function.

  16. Oral salmon calcitonin enhances insulin action and glucose metabolism in diet-induced obese streptozotocin-diabetic rats.

    PubMed

    Feigh, Michael; Hjuler, Sara T; Andreassen, Kim V; Gydesen, Sofie; Ottosen, Ida; Henriksen, Jan Erik; Beck-Nielsen, Henning; Christiansen, Claus; Karsdal, Morten A; Henriksen, Kim

    2014-08-15

    We previously reported that oral delivery of salmon calcitonin (sCT) improved energy and glucose homeostasis and attenuated diabetic progression in animal models of diet-induced obesity (DIO) and type 2 diabetes, although the glucoregulatory mode of action was not fully elucidated. In the present study we hypothesized that oral sCT as pharmacological intervention 1) exerted anti-hyperglycemic efficacy, and 2) enhanced insulin action in DIO-streptozotocin (DIO-STZ) diabetic rats. Diabetic hyperglycemia was induced in male selectively bred DIO rats by a single low dose (30mg/kg) injection of STZ. Oral sCT by gavage was delivered as once-daily administration with lead-in (2mg/kg) and maintenance (0.5mg/kg) dose of oral sCT for a total of 21 days. Food intake, body weight, blood glucose, HbA1c, glucose and insulin tolerance test, and parameters of insulin sensitivity were investigated. Plasma glucoregulatory hormones and pancreatic insulin content were analyzed. Oral sCT treatment induced a pronounced anorectic action during the 7 days lead-in period and markedly reduced food intake and body weight in conjunction with improved glucose homeostasis. During the maintenance period, oral sCT normalized food intake and attenuated weight loss, albeit sustained glycemic control by reducing fasting blood glucose and HbA1c levels compared to those of vehicle-treated rats at the end of study. Notably, plasma levels of insulin, glucagon, leptin and adiponectin were unaltered, albeit insulin action was enhanced in conjunction with protection of pancreatic insulin content. The results of the present study indicate that oral sCT exerts a novel insulin-sensitizing effect to improve glucose metabolism in obesity and type 2 diabetes.

  17. Diets Containing α-Linolenic (ω3) or Oleic (ω9) Fatty Acids Rescues Obese Mice From Insulin Resistance.

    PubMed

    Oliveira, V; Marinho, R; Vitorino, D; Santos, G A; Moraes, J C; Dragano, N; Sartori-Cintra, A; Pereira, L; Catharino, R R; da Silva, A S R; Ropelle, E R; Pauli, J R; De Souza, C T; Velloso, L A; Cintra, D E

    2015-11-01

    Subclinical systemic inflammation is a hallmark of obesity and insulin resistance. The results obtained from a number of experimental studies suggest that targeting different components of the inflammatory machinery may result in the improvement of the metabolic phenotype. Unsaturated fatty acids exert antiinflammatory activity through several distinct mechanisms. Here, we tested the capacity of ω3 and ω9 fatty acids, directly from their food matrix, to exert antiinflammatory activity through the G protein-coupled receptor (GPR)120 and GPR40 pathways. GPR120 was activated in liver, skeletal muscle, and adipose tissues, reverting inflammation and insulin resistance in obese mice. Part of this action was also mediated by GPR40 on muscle, as a novel mechanism described. Pair-feeding and immunoneutralization experiments reinforced the pivotal role of GPR120 as a mediator in the response to the nutrients. The improvement in insulin sensitivity in the high-fat substituted diets was associated with a marked reduction in tissue inflammation, decreased macrophage infiltration, and increased IL-10 levels. Furthermore, improved glucose homeostasis was accompanied by the reduced expression of hepatic gluconeogenic enzymes and reduced body mass. Thus, our data indicate that GPR120 and GPR40 play a critical role as mediators of the beneficial effects of dietary unsaturated fatty acids in the context of obesity-induced insulin resistance.

  18. Small Molecule Kaempferol Promotes Insulin Sensitivity and Preserved Pancreatic β -Cell Mass in Middle-Aged Obese Diabetic Mice.

    PubMed

    Alkhalidy, Hana; Moore, William; Zhang, Yanling; McMillan, Ryan; Wang, Aihua; Ali, Mostafa; Suh, Kyung-Shin; Zhen, Wei; Cheng, Zhiyong; Jia, Zhenquan; Hulver, Matthew; Liu, Dongmin

    2015-01-01

    Insulin resistance and a progressive decline in functional β-cell mass are hallmarks of developing type 2 diabetes (T2D). Thus, searching for natural, low-cost compounds to target these two defects could be a promising strategy to prevent the pathogenesis of T2D. Here, we show that dietary intake of flavonol kaempferol (0.05% in the diet) significantly ameliorated hyperglycemia, hyperinsulinemia, and circulating lipid profile, which were associated with the improved peripheral insulin sensitivity in middle-aged obese mice fed a high-fat (HF) diet. Kaempferol treatment reversed HF diet impaired glucose transport-4 (Glut4) and AMP-dependent protein kinase (AMPK) expression in both muscle and adipose tissues from obese mice. In vitro, kaempferol increased lipolysis and prevented high fatty acid-impaired glucose uptake, glycogen synthesis, AMPK activity, and Glut4 expression in skeletal muscle cells. Using another mouse model of T2D generated by HF diet feeding and low doses of streptozotocin injection, we found that kaempferol treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in obese diabetic mice, which are associated with the improved islet β-cell mass. These results demonstrate that kaempferol may be a naturally occurring anti-diabetic agent by improving peripheral insulin sensitivity and protecting against pancreatic β-cell dysfunction.

  19. The Association of Metabolic Syndrome, Insulin Resistance and Non-alcoholic Fatty Liver Disease in Overweight/Obese Children

    PubMed Central

    El-Koofy, Nehal M.; Anwar, Ghada M.; El-Raziky, Mona S.; El-Hennawy, Ahmad M.; El-Mougy, Fatma M.; El-Karaksy, Hanaa M.; Hassanin, Fetouh M.; Helmy, Heba M.

    2012-01-01

    Background/Aim: To study the prevalence of metabolic syndrome (MS), insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) in overweight/obese children with clinical hepatomegaly and/or raised alanine aminotransferase (ALT). Patients and Methods: Thirty-three overweight and obese children, aged 2-13 years, presenting with hepatomegaly and/or raised ALT, were studied for the prevalence of MS, IR and NAFLD. Laboratory analysis included fasting blood glucose, serum insulin, serum triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and liver biochemical profile, in addition to liver ultrasound and liver biopsy. Results: Twenty patients (60.6%) were labeled with MS. IR was present in 16 (48.4%). Fifteen (44%) patients had biopsy-proven NAFLD. Patients with MS were more likely to have NAFLD by biopsy (P=0.001). Children with NAFLD had significantly higher body mass index, waist circumference, ALT, total cholesterol, LDL-c, TG, fasting insulin, and lower HDL-c compared to patients with normal liver histology (P< 0.05) and fitted more with the criteria of MS (80% vs. 44%). IR was significantly more common among NAFLD patients (73% vs. 28%). Conclusion: There is a close association between obesity, MS, IR and NAFLD. Obese children with clinical or biochemical hepatic abnormalities are prone to suffer from MS, IR and NAFLD. PMID:22249092

  20. Adipose-specific deletion of Kif5b exacerbates obesity and insulin resistance in a mouse model of diet-induced obesity.

    PubMed

    Cui, Ju; Pang, Jing; Lin, Ya-Jun; Gong, Huan; Wang, Zhen-He; Li, Yun-Xuan; Li, Jin; Wang, Zai; Jiang, Ping; Dai, Da-Peng; Li, Jian; Cai, Jian-Ping; Huang, Jian-Dong; Zhang, Tie-Mei

    2017-02-27

    Recent studies have shown that KIF5B (conventional kinesin heavy chain) mediates glucose transporter type 4 translocation and adiponectin secretion in 3T3-L1 adipocytes, suggesting an involvement of KIF5B in the homeostasis of metabolism. However, the in vivo physiologic function of KIF5B in adipose tissue remains to be determined. In this study, adipose-specific Kif5b knockout (F-K5bKO) mice were generated using the Cre-LoxP strategy. F-K5bKO mice had similar body weights to controls fed on a standard chow diet. However, F-K5bKO mice had hyperlipidemia and significant glucose intolerance and insulin resistance. Deletion of Kif5b aggravated the deleterious impact of a high-fat diet (HFD) on body weight gain, hepatosteatosis, glucose tolerance, and systematic insulin sensitivity. These changes were accompanied by impaired insulin signaling, decreased secretion of adiponectin, and increased serum levels of leptin and proinflammatory adipokines. F-K5bKO mice fed on a HFD exhibited lower energy expenditure and thermogenic dysfunction as a result of whitening of brown adipose due to decreased mitochondria biogenesis and down-regulation of key thermogenic gene expression. In conclusion, selective deletion of Kif5b in adipose tissue exacerbates HFD-induced obesity and its associated metabolic disorders, partly through a decrease in energy expenditure, dysregulation of adipokine secretion, and insulin signaling.-Cui, J., Pang, J., Lin, Y.-J., Gong, H., Wang, Z.-H., Li, Y.-X., Li, J., Wang, Z., Jiang, P., Dai, D.-P., Li, J., Cai, J.-P., Huang, J.-D., Zhang, T.-M. Adipose-specific deletion of Kif5b exacerbates obesity and insulin resistance in a mouse model of diet-induced obesity.

  1. The apelinergic system: sexual dimorphism and tissue-specific modulations by obesity and insulin resistance in female mice.

    PubMed

    Butruille, Laura; Drougard, Anne; Knauf, Claude; Moitrot, Emmanuelle; Valet, Philippe; Storme, Laurent; Deruelle, Philippe; Lesage, Jean

    2013-08-01

    It has been proposed that the apelinergic system (apelin and its receptor APJ) may be a promising therapeutic target in obesity-associated insulin resistance syndrome. However, due to the extended tissue-distribution of this system, the therapeutic use of specific ligands for APJ may target numerous tissues resulting putatively to collateral deleterious effects. To unravel specific tissular dysfunctions of this system under obesity and insulin-resistance conditions, we measured the apelinemia and gene-expression level of both apelin (APL) and APJ in 12-selected tissues of insulin-resistant obese female mice fed with a high fat (HF) diet. In a preliminary study, we compared between adult male and female mice, the circadian plasma apelin variation and the effect of fasting on apelinemia. No significant differences were found for these parameters suggesting that the apelinemia is not affected by the sex. Moreover, plasma apelin level was not modulated during the four days of the estrous cycle in females. In obese and insulin-resistant HF female mice, plasma apelin concentration after fasting was not modified but, the gene-expression level of the APL/APJ system was augmented in the white adipose tissue (WAT) and reduced in the brown adipose tissue (BAT), the liver and in kidneys. BAT apelin content was reduced in HF female mice. Our data suggest that the apelinergic system may be implicated into specific dysfunctions of these tissues under obesity and diabetes and that, pharmacologic modulations of this system may be of interest particularly in the treatment of adipose, liver and renal dysfunctions that occur during these pathologies.

  2. Obesity and insulin resistance induce early development of diastolic dysfunction in young female mice fed a Western diet.

    PubMed

    Manrique, Camila; DeMarco, Vincent G; Aroor, Annayya R; Mugerfeld, Irina; Garro, Mona; Habibi, Javad; Hayden, Melvin R; Sowers, James R

    2013-10-01

    Cardiovascular disease (CVD), including heart failure, constitutes the main source of morbidity and mortality in men and women with diabetes. Although healthy young women are protected against CVD, postmenopausal and diabetic women lose this CVD protection. Obesity, insulin resistance, and diabetes promote heart failure in females, and diastolic dysfunction is the earliest manifestation of this heart failure. To examine the mechanisms promoting diastolic dysfunction in insulin-resistant females, this investigation evaluated the impact of 8 weeks of a high-fructose/high-fat Western diet (WD) on insulin sensitivity and cardiac structure and function in young C57BL6/J female versus male mice. Insulin sensitivity was determined by hyperinsulinemic-euglycemic clamps and two-dimensional echocardiograms were used to evaluate cardiac function. Both males and females developed systemic insulin resistance after 8 weeks of a WD. However, only the females developed diastolic dysfunction. The diastolic dysfunction promoted by the WD was accompanied by increases in collagen 1, a marker of stiffness, increased oxidative stress, reduced insulin metabolic signaling, and increased mitochondria and cardiac microvascular alterations as determined by electron microscopy. Aldosterone (a promoter of cardiac stiffness) levels were higher in females compared with males but were not affected by the WD in either gender. These data suggest a predisposition toward developing early diastolic heart failure in females exposed to a WD. These data are consistent with the notion that higher aldosterone levels, in concert with insulin resistance, may promote myocardial stiffness and diastolic dysfunction in response to overnutrition in females.

  3. Acute insulin-induced elevations of circulating leptin and feeding inhibition in lean but not obese rats.

    PubMed

    Singh, Kimberly A; Boozer, Carol N; Vasselli, Joseph R

    2005-08-01

    Insulin has been shown to stimulate leptin mRNA expression acutely in rat adipose tissue, but its short-term effects on circulating leptin levels, and subsequent feeding behavior, have not been well described. We used 11-mo-old female selectively bred obesity-resistant (OR) and obesity-prone (OP) Sprague-Dawley rats maintained on laboratory chow to investigate this question. At testing, body weights and basal leptin levels of the OP rats were significantly elevated compared with the OR rats. In the 3-h fasted state, injection of 2.0 U insulin/kg ip resulted in significant elevations of plasma leptin at 4 h postinjection in both OP and OR groups (hour 4, +2.50 and +5.98 ng/ml, respectively). In separate feeding tests with the same groups, intake of laboratory chow pellets was significantly inhibited during hours 2-4 after 2.0 U/kg of insulin in the OR (-80.1%, P < 0.05), but not in the OP group, compared with intake after saline injections. In feeding tests with palatable moderately high-fat pellets after 2.0 and 3.0 U insulin/kg ip, significant decreases between hours 2 and 4 in intake were seen in the OR group only (-41.0 and -68.3%, respectively). Thus feeding inhibition coincides with insulin-induced elevations of plasma leptin in lean but not obese Sprague-Dawley rats. Our data suggest that elevations of leptin within the physiological range may contribute to short-term inhibition of food intake in rats and that this process may be stimulated by feeding-related insulin release.

  4. Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice

    SciTech Connect

    Verreth, Wim; Verhamme, Peter; Pelat, Michael; Ganame, Javier; Bielicki, John K.; Mertens, Ann; Quarck, Rozenn; Benhabiles, Nora; Marguerie, Gerard; Mackness, Bharti; Mackness, Mike; Ninio, Ewa; Herregods, Marie-Christine; Balligand, Jean-Luc; Holvoet, Paul

    2003-09-01

    Weight-loss in obese insulin-resistant, but not in insulin-sensitive, persons reduces CHD risk. It is not known to what extent changes in the adipose gene expression profile are important for reducing CHD risk. We studied the effect of diet restriction-induced weight-loss on gene expression in adipose tissue, atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia and insulin-resistance are associated with hypertension, impaired left ventricle function and accelerated atherosclerosis in those mice. Diet restriction during 12 weeks caused a 45% weight-loss and changes in the gene expression in adipose tissue of PPARa and PPAR? and of key genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. These changes were associated with increased insulin-sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. Thus, induction of PPARa and PPAR? in adipose tissue is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight-loss. Our observations point to the critical role of PPARs in the pathogenesis of cardiovascular features of the metabolic syndrome.

  5. Changes in body weight are significantly associated with changes in fasting plasma glucose and HDL cholesterol in Japanese men without abdominal obesity (waist circumference < 85 cm).

    PubMed

    Oda, Eiji; Kawai, Ryu

    2011-06-01

    The aims are to examine whether changes in body weight (dBW) are associated with changes in cardiovascular risk factors in Japanese men without abdominal obesity (waist circumference (WC) < 85 cm) and which anthropometric index, dBW or changes in WC (dWC), is more strongly associated with changes in cardiovascular risk factors in men without abdominal obesity. It is a retrospective study in 692 Japanese men without abdominal obesity who took annual health screening tests consecutively over one year. Standardized linear regression coefficients (SRCs) of dBW and dWC were calculated for changes in systolic blood pressure (dSBP), diastolic blood pressure (dDBP), fasting plasma glucose (dFPG), triglycerides (dTG), HDL cholesterol (dHDL), and high-sensitivity C-reactive protein (dCRP). The SRCs of dBW for dFPG and dHDL were significant in all men and in men with each risk factor corresponding to the component of metabolic syndrome (MetS). The SRCs of dWC for dTG and dCRP were significant in all men but not in men with each risk factor corresponding to the MetS component. In conclusions, dBW were significantly associated with dFPG and dHDL in Japanese men without abdominal obesity. Therefore, abdominal obesity should not be considered as a necessary component of MetS in Japanese men. dBW may be more useful than dWC as a marker of changes in cardiovascular risk factors in lifestyle intervention programs.

  6. Effects of Native Banana Starch Supplementation on Body Weight and Insulin Sensitivity in Obese Type 2 Diabetics

    PubMed Central

    Ble-Castillo, Jorge L.; Aparicio-Trápala, María A.; Francisco-Luria, Mateo U.; Córdova-Uscanga, Rubén; Rodríguez-Hernández, Arturo; Méndez, José D.; Díaz-Zagoya, Juan C.

    2010-01-01

    Few fiber supplements have been studied for physiological effectiveness. The effects of native banana starch (NBS) and soy milk (control) on body weight and insulin sensitivity in obese type 2 diabetics were compared using a blind within-subject crossover design. Subjects undertook two phases of 4-week supplementation either with NBS or soy milk. Patients on NBS lost more body weight than when they were on control treatment. Plasma insulin and HOMA-I were reduced after NBS consumption, compared with baseline levels, but not significantly when compared to the control treatment. Results support the use of NBS as part of dietary fiber supplementation. PMID:20623003

  7. [Relationship between serum levels of C-reactive protein and alpha1-antitrypsin and insulin resistance in obese women].

    PubMed

    Ramírez Alvarado, María Matilde; Sánchez Roitz, César

    2014-09-01

    Adipose tissue produces cytokines involved in insulin resistance (IR) such as IL-6, IL-8, TNF-alpha and proinflammatory molecules such as C reactive protein (CRP). alpha1-antitrypsin is an inflammation-sensitive plasma protein. The objective of this study is to determine the correlation between serum CRP high-sensitivity (CRPhs) and alpha1-antitrypsin levels with IR indices in obese Venezuelan women. The study population consisted of 15 normal weight women (BMI 21.8 +/- 1.9 kg/m2) and 15 obese women (BMI 35.3 +/- 5.3 kg/m2). Obese and lean women underwent a 2 h-75 g oral glucose tolerance test and the following indices were calculated: homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of beta cell function (HOMA-beta), Matsuda Index and Insulinogenic Index. The relationship between serum CRPhs and alpha1-antitrypsin levels and these indices were determined. Obese women had higher CRPhs levels (p = 0.001) compared with normal weight women. In obese women, serum CRPhs levels were positively correlated with HOMA-IR (r = 0.73, p = 0.0021), HOMA-beta (r = 0.53, p = 0.031) and negatively correlated with the Matsuda Index (r = -0.60, p = 0.017). No correlation between serum levels of alpha1-antitrypsin and IR indices in the obese group and the lean group was observed. There was a relation between serum CRPhs levels and insulin resistance, suggesting a role of subclinical inflammation in IR.

  8. Role of microRNAs on adipogenesis, chronic low-grade inflammation, and insulin resistance in obesity.

    PubMed

    Cruz, Kyria Jayanne Clímaco; de Oliveira, Ana Raquel Soares; Morais, Jennifer Beatriz Silva; Severo, Juliana Soares; Marreiro PhD, Dilina do Nascimento

    2017-03-01

    The aim of this review was to convey updated information on the role of microRNAs in adipogenesis, chronic low-grade inflammation, and insulin resistance in obesity. Obesity is a chronic disease characterized by the presence of metabolic disorders (e.g., low-grade chronic inflammation), which contributes to the manifestation of insulin resistance. Diverse molecular mechanisms have been implicated in the development of these disorders, and microRNAs stand out as a contributing factor. They are a class of noncoding RNAs that regulate the expression of genes by inducing cleavage of mRNAs or via inhibition of protein translation. It is important to point out that obese individuals show alterations in the expression of microRNAs favoring manifestation of the metabolic disorders present in these patients, and these alterations may be reversed by the loss of weight. Therefore, microRNAs may be regarded as potential biomarkers of obesity-related disorders. Further studies on this topic may advance the understanding of the molecular basis of obesity, including the participation of microRNAs in the pathogenesis of this disease.

  9. AMPK Activation by Metformin Suppresses Abnormal Extracellular Matrix Remodeling in Adipose Tissue and Ameliorates Insulin Resistance in Obesity.

    PubMed

    Luo, Ting; Nocon, Allison; Fry, Jessica; Sherban, Alex; Rui, Xianliang; Jiang, Bingbing; Xu, X Julia; Han, Jingyan; Yan, Yun; Yang, Qin; Li, Qifu; Zang, Mengwei

    2016-08-01

    Fibrosis is emerging as a hallmark of metabolically dysregulated white adipose tissue (WAT) in obesity. Although adipose tissue fibrosis impairs adipocyte plasticity, little is known about how aberrant extracellular matrix (ECM) remodeling of WAT is initiated during the development of obesity. Here we show that treatment with the antidiabetic drug metformin inhibits excessive ECM deposition in WAT of ob/ob mice and mice with diet-induced obesity, as evidenced by decreased collagen deposition surrounding adipocytes and expression of fibrotic genes including the collagen cross-linking regulator LOX Inhibition of interstitial fibrosis by metformin is likely attributable to the activation of AMPK and the suppression of transforming growth factor-β1 (TGF-β1)/Smad3 signaling, leading to enhanced systemic insulin sensitivity. The ability of metformin to repress TGF-β1-induced fibrogenesis is abolished by the dominant negative AMPK in primary cells from the stromal vascular fraction. TGF-β1-induced insulin resistance is suppressed by AMPK agonists and the constitutively active AMPK in 3T3L1 adipocytes. In omental fat depots of obese humans, interstitial fibrosis is also associated with AMPK inactivation, TGF-β1/Smad3 induction, aberrant ECM production, myofibroblast activation, and adipocyte apoptosis. Collectively, integrated AMPK activation and TGF-β1/Smad3 inhibition may provide a potential therapeutic approach to maintain ECM flexibility and combat chronically uncontrolled adipose tissue expansion in obesity.

  10. Adipose tissue macrophages in the Development of Obesity-induced Inflammation, Insulin Resistance and Type 2 Diabetes

    PubMed Central

    Lee, Jongsoon

    2014-01-01

    It has been increasingly accepted that chronic subacute inflammation plays an important role in the development of insulin resistance and Type 2 Diabetes in animals and humans. Particularly supporting this is that suppression of systemic inflammation in Type 2 Diabetes improves glycemic control; this also points to a new potential therapeutic target for the treatment of Type 2 Diabetes. Recent studies strongly suggest that obesity-induced inflammation is mainly mediated by tissue resident immune cells, with particular attention being focused on adipose tissue macrophages (ATMs). This review delineates the current progress made in understanding obesity-induced inflammation and the roles ATMs play in this process. PMID:23397293

  11. Adipose Estrogen and Increased Breast Cancer Risk in Obesity: Regulation by Leptin and Insulin

    DTIC Science & Technology

    2006-09-01

    associated with insulin resistance we had also proposed to determine the induction of Aromatase and βHSD5 mRNA expression in response to insulin and...Metabolic insulin resistance was determined by measuring insulin mediated glucose uptake. Glucose uptake was reduced by 50-70% in adipocytes...conditions in our cell culture system to mimic metabolic insulin resistance . These “insulin-resistant” adipocytes are currently being used to

  12. The Roles of Adipokines, Proinflammatory Cytokines, and Adipose Tissue Macrophages in Obesity-Associated Insulin Resistance in Modest Obesity and Early Metabolic Dysfunction

    PubMed Central

    Kim, Ji Min; Joung, Kyong Hye; Lee, Ju Hee; You, Bo Ram; Choi, Min Jeong; Ryu, Min Jeong; Ko, Young Bok; Lee, Min A.; Lee, Junguee; Ku, Bon Jeong; Shong, Minho; Lee, Ki Hwan; Kim, Hyun Jin

    2016-01-01

    The roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in obesity-associated insulin resistance have been explored in both animal and human studies. However, our current understanding of obesity-associated insulin resistance relies on studies of artificial metabolic extremes. The purpose of this study was to explore the roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in human patients with modest obesity and early metabolic dysfunction. We obtained omental adipose tissue and fasting blood samples from 51 females undergoing gynecologic surgery. We investigated serum concentrations of proinflammatory cytokines and adipokines as well as the mRNA expression of proinflammatory and macrophage phenotype markers in visceral adipose tissue using ELISA and quantitative RT-PCR. We measured adipose tissue inflammation and macrophage infiltration using immunohistochemical analysis. Serum levels of adiponectin and leptin were significantly correlated with HOMA-IR and body mass index. The levels of expression of MCP-1 and TNF-α in visceral adipose tissue were also higher in the obese group (body mass index ≥ 25). The expression of mRNA MCP-1 in visceral adipose tissue was positively correlated with body mass index (r = 0.428, p = 0.037) but not with HOMA-IR, whereas TNF-α in visceral adipose tissue was correlated with HOMA-IR (r = 0.462, p = 0.035) but not with body mass index. There was no obvious change in macrophage phenotype or macrophage infiltration in patients with modest obesity or early metabolic dysfunction. Expression of mRNA CD163/CD68 was significantly related to mitochondrial-associated genes and serum inflammatory cytokine levels of resistin and leptin. These results suggest that changes in the production of inflammatory biomolecules precede increased immune cell infiltration and induction of a macrophage phenotype switch in visceral adipose tissue. Furthermore, serum resistin and leptin have specific

  13. DELETION OF PROTEIN TYROSINE PHOSPHATASE 1B IMPROVES PERIPHERAL INSULIN RESISTANCE AND VASCULAR FUNCTION IN OBESE, LEPTIN RESISTANT MICE VIA REDUCED OXIDANT TONE

    PubMed Central

    Ali, M. Irfan; Ketsawatsomkron, Pimonrat; Belin de Chantelemele, Eric J.; Mintz, James D.; Muta, Kenjiro; Salet, Christina; Black, Stephen M.; Tremblay, Michel L.; Fulton, David J.; Marrero, Mario B.; Stepp, David W.

    2009-01-01

    Rationale Obesity is a risk factor for cardiovascular dysfunction, yet the underlying factors driving this impaired function remain poorly understood. Insulin resistance is a common pathology in obese patients and has been shown to impair vascular function. Whether insulin resistance or obesity, itself, is causal remains unclear. Objective The current study tested the hypothesis that insulin resistance is the underlying mediator for impaired nitric oxide mediated dilation in obesity by genetic deletion of the insulin-desensitizing enzyme protein tyrosine phosphatase 1B (PTP1B) in db/db mice. Methods and Results The db/db mouse is morbidly obese, insulin resistant and has tissue-specific elevation in PTP1B expression compared to lean controls. In db/db mice, PTP1B deletion improved glucose clearance, dyslipidemia, and insulin receptor signaling in muscle and fat. Hepatic insulin signaling in db/db mice was not improved by deletion of PTP1B, indicating specific amelioration of peripheral insulin resistance. Additionally, obese mice demonstrate an impaired endothelium dependent and independent vasodilation to acetylcholine and sodium nitroprusside, respectively. This impairment, which correlated with increased superoxide in the db/db mice, was corrected by superoxide scavenging. Increased superoxide production was associated with increased expression of NAD(P)H Oxidase 1 and its molecular regulators, Noxo1 and Noxa1. Conclusion Deletion of PTP1B improved both endothelium dependent and independent nitric oxide mediated dilation and reduced superoxide generation in db/db mice. PTP1B deletion did not affect any vascular function in lean mice. Taken together, these data reveal a role for peripheral insulin resistance as the mediator of vascular dysfunction in obesity. PMID:19797171

  14. Uncoupling of Obesity from Insulin Resistance Through a Targeted Mutation in aP2, the Adipocyte Fatty Acid Binding Protein

    NASA Astrophysics Data System (ADS)

    Hotamisligil, Gokhan S.; Johnson, Randall S.; Distel, Robert J.; Ellis, Ramsey; Papaioannou, Virginia E.; Spiegelman, Bruce M.

    1996-11-01

    Fatty acid binding proteins (FABPs) are small cytoplasmic proteins that are expressed in a highly tissue-specific manner and bind to fatty acids such as oleic and retinoic acid. Mice with a null mutation in aP2, the gene encoding the adipocyte FABP, were developmentally and metabolically normal. The aP2-deficient mice developed dietary obesity but, unlike control mice, they did not develop insulin resistance or diabetes. Also unlike their obese wild-type counterparts, obese aP2-/- animals failed to express in adipose tissue tumor necrosis factor-α (TNF-α), a molecule implicated in obesity-related insulin resistance. These results indicate that aP2 is central to the pathway that links obesity to insulin resistance, possibly by linking fatty acid metabolism to expression of TNF-α.

  15. The association between abdominal obesity and characteristics of migraine attacks in Iranian adults

    PubMed Central

    Sadeghi, Omid; Askari, Gholamreza; Maghsoudi, Zahra; Ghiasvand, Reza; Khorvash, Fariborz

    2016-01-01

    Background: Migraine is a primary headache disorder that affects the neurovascular system. Recent studies have shown that migraine patients with general obesity have higher characteristics of migraine attacks compared with normal weight patients, but data on central obesity are scarce. This study was done to assess the relationship between central obesity and the characteristics of migraine attacks in migraine patients. Materials and Methods: This cross-sectional study was conducted on 129 migraine patients (28 men and 101 women), aged 15–67 years, in Isfahan, Iran. Anthropometric measurements such as waist circumference (WC), hip circumference (HC), waist–hip ratio (WHR) and waist–height ratio (WHtR), as well as characteristics of migraine attacks such as severity, frequency, duration, and headache diary result (HDR) was determined for each participant. Linear regression was used to examine the association between anthropometric measurements and characteristics of migraine attacks. P value less than 0.05 was considered significant. Results: WC, WHR, and WHtR were positively associated with the severity (P-value: WC: 0.002, WHR: 0.002, WHtR: 0.001) and frequency (P-value: WC: 0.006, WHR: 0.01, WHtR: 0.002) of migraine attacks. Moreover, we found a significant association between WC (P = 0.001), WHR (P = 0.004), and WHtR (P < 0.001) with HDR. No significant relationship was observed between central obesity indicators and duration of migraine attacks. Conclusions: Central obesity indicators were positively associated with the severity and frequency of migraine attacks as well as HDR, but not with duration of attacks. Based on our findings, it can be concluded that weight loss may decrease the characteristics of migraine attacks. PMID:27186204

  16. Insulin and Insulin Resistance

    PubMed Central

    2005-01-01

    As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, structure, synthesis, secretion, actions and interactions followed by a discussion of insulin resistance and its associated clinical manifestations. Specific areas of focus include the actions of insulin and manifestations of insulin resistance in specific organs and tissues, physiological, environmental and pharmacological influences on insulin action and insulin resistance as well as clinical syndromes associated with insulin resistance. Clinical and functional measures of insulin resistance are also covered. Despite our incomplete understanding of the complex biological mechanisms of insulin action and insulin resistance, we need to consider the dramatic social changes of the past century with respect to physical activity, diet, work, socialisation and sleep patterns. Rapid globalisation, urbanisation and industrialisation have spawned epidemics of obesity, diabetes and their attendant co-morbidities, as physical inactivity and dietary imbalance unmask latent predisposing genetic traits. PMID:16278749

  17. Infrequent breakfast consumption is associated with higher body adiposity and abdominal obesity in Malaysian school-aged adolescents.

    PubMed

    Nurul-Fadhilah, Abdullah; Teo, Pey Sze; Huybrechts, Inge; Foo, Leng Huat

    2013-01-01

    Unhealthy dietary pattern increases the risk of obesity and metabolic disorders in growing children and adolescents. However, the way the habitual pattern of breakfast consumption influences body composition and risk of obesity in adolescents is not well defined. Thus, the aim of the present study was to assess any associations between breakfast consumption practices and body composition profiles in 236 apparently healthy adolescents aged 12 to 19 years. A self-administered questionnaire on dietary behaviour and lifestyle practices and a dietary food frequency questionnaire were used. Body composition and adiposity indices were determined using standard anthropometric measurement protocols and dual energy χ-ray absorptiometry (DXA). Mean age of the participants was 15.3±1.9 years. The majority of participants (71.2%) fell in the normal body mass index (BMI) ranges. Breakfast consumption patterns showed that only half of the participants (50%) were consuming breakfast daily. Gender-specific multivariate analyses (ANCOVA) showed that in both boys and girls, those eating breakfast at least 5 times a week had significantly lower body weight, body mass index (BMI), BMI z-scores, waist circumference, body fat mass and percent body fat (%BF) compared to infrequent breakfast eaters, after adjustment for age, household income, pubertal status, eating-out and snacking practices, daily energy intakes, and daily physical activity levels. The present findings indicate that infrequent breakfast consumption is associated with higher body adiposity and abdominal obesity. Therefore, daily breakfast consumption with healthy food choices should be encouraged in growing children and adolescents to prevent adiposity during these critical years of growth.

  18. Obesity-related dyslipidemia associated with FAAH, independent of insulin response, in multigenerational families of Northern European descent

    PubMed Central

    Zhang, Yi; Sonnenberg, Gabriele E; Baye, Tesfaye Mersha; DeLaForest, Jack Ann; MacKinney, Erin; Hillard, Cecilia J; Kissebah, Ahmed H; Olivier, Michael; Wilke, Russell A

    2010-01-01

    A more thorough understanding of the genetic architecture underlying obesity-related lipid disorders could someday facilitate cardiometabolic risk reduction through early clinical intervention based upon improved characterization of individual risk. In recent years, there has been tremendous interest in understanding the endocannabinoid system as a novel therapeutic target for the treatment of obesity-related dyslipidemia. Aims N-arachidonylethanolamine activates G-protein-coupled receptors within the endocannabinoid system. Fatty acid amide hydrolase (FAAH) is a primary catabolic regulator of N-acylethanolamines, including arachidonylethanolamine. Genetic variants in FAAH have inconsistently been associated with obesity. It is conceivable that genetic variability in FAAH directly influences lipid homeostasis. The current study characterizes the relationship between FAAH and obesity-related dyslipidemia, in one of the most rigorously-phenotyped obesity study cohorts in the USA. Materials & methods Members of 261 extended families (pedigrees ranging from 4 to 14 individuals) were genotyped using haplotype tagging SNPs obtained for the FAAH locus, including 5 kb upstream and 5 kb downstream. Each SNP was tested for basic obesity-related phenotypes (BMI, waist and hip circumference, waist:hip ratio, fasting glucose, fasting insulin and fasting lipid levels) in 1644 individuals within these 261 families. Each SNP was also tested for association with insulin responsiveness using data obtained from a frequently sampled intravenous glucose tolerance test in 399 individuals (32 extended families). Results A well characterized coding SNP in FAAH (rs324420) was associated with increased BMI, increased triglycerides, and reduced levels of high-density lipoprotein cholesterol. Mean (standard deviation) high-density lipoprotein cholesterol level was 40.5 (14.7) mg/dl for major allele homozygotes, 39.1 (10.4) mg/dl for heterozygotes, and 34.8 (8.1) mg/dl for minor allele

  19. Magnetic Resonance Imaging of Changes in Abdominal Compartments in Obese Diabetics during a Low-Calorie Weight-Loss Program

    PubMed Central

    Vogt, Lena J.; Steveling, Antje; Meffert, Peter J.; Kromrey, Marie-Luise; Kessler, Rebecca; Hosten, Norbert; Krüger, Janine; Gärtner, Simone; Aghdassi, Ali A.; Mayerle, Julia; Lerch, Markus M.; Kühn, Jens-Peter

    2016-01-01

    Objectives To investigate changes in the fat content of abdominal compartments and muscle area during weight loss using confounder-adjusted chemical-shift-encoded magnetic resonance imaging (MRI) in overweight diabetics. Methods Twenty-nine obese diabetics (10/19 men/women, median age: 59.0 years, median body mass index (BMI): 34.0 kg/m2) prospectively joined a standardized 15-week weight-loss program (six weeks of formula diet exclusively, followed by reintroduction of regular food with gradually increasing energy content over nine weeks) over 15 weeks. All subjects underwent a standardized MRI protocol including a confounder-adjusted chemical-shift-encoded MR sequence with water/fat separation before the program as well at the end of the six weeks of formula diet and at the end of the program at 15 weeks. Fat fractions of abdominal organs and vertebral bone marrow as well as volumes of visceral and subcutaneous fat were determined. Furthermore, muscle area was evaluated using the L4/L5 method. Data were compared using the Wilcoxon signed-rank test for paired samples. Results Median BMI decreased significantly from 34.0 kg/m2 to 29.9 kg/m2 (p < 0.001) at 15 weeks. Liver fat content was normalized (14.2% to 4.1%, p < 0.001) and vertebral bone marrow fat (57.5% to 53.6%, p = 0.018) decreased significantly throughout the program, while fat content of pancreas (9.0%), spleen (0.0%), and psoas muscle (0.0%) did not (p > 0.15). Visceral fat volume (3.2 L to 1.6 L, p < 0.001) and subcutaneous fat diameter (3.0 cm to 2.2 cm, p < 0.001) also decreased significantly. Muscle area declined by 6.8% from 243.9 cm2 to 226.8 cm2. Conclusion MRI allows noninvasive monitoring of changes in abdominal compartments during weight loss. In overweight diabetics, weight loss leads to fat reduction in abdominal compartments, such as visceral fat, as well as liver fat and vertebral bone marrow fat while pancreas fat remains unchanged. PMID:27110719

  20. Rapid Deterioration of Insulin Secretion in Obese Adolescents Preceding the Onset of Type 2 Diabetes

    PubMed Central

    Elder, Deborah A.; Hornung, Lindsey N.; Herbers, Patricia M.; Prigeon, Ron; Woo, Jessica G.; D'Alessio, David A.

    2014-01-01

    Objective To identify pathophysiologic changes that lead to the onset of type 2 diabetes (T2DM) in adolescents. Study design Obese adolescents with NGT (n=41) were studied longitudinally over 4 years with serial measure of the acute insulin response to IV glucose (AIRg) as well as proinsulin (PI) concentrations. Insulin resistance was estimated with HOMA modeling, the disposition index (DI) computed as AIRg × 1/HOMA-IR, and IV glucose tolerance estimated as the glucose disappearance constant (kg). Results Four adolescents developed diabetes during the study (DM), and the rest of the cohort remained non-diabetic (NDM). Baseline PI exceeded the interquartile range of the NDM group in 3 of 4 subjects with DM and all had > 85% reduction from baseline AIRg, and DI, within 6 months of diagnosis. All the subjects with DM gained weight over the course of the study but these changes paralleled those for the NDM group. HOMA-IR increased substantially in 1 of the subjects with DM at the time of diagnosis, but was comparable with baseline in the other 3. The DI and kg of the subjects with DM was below the 10th percentile of the NDM group before and after diagnosis. Conclusion Conversion from NGT to T2DM in adolescents can occur rapidly, and T2DM onset is heralded by a substantial decline in AIRg and DI, as well as increased release of PI. These results support loss of beta-cell function as the proximate step in the development of T2DM in this age group. PMID:25557969

  1. The expression of genes involved in jejunal lipogenesis and lipoprotein synthesis is altered in morbidly obese subjects with insulin resistance.

    PubMed

    Gutierrez-Repiso, Carolina; Rodriguez-Pacheco, Francisca; Garcia-Arnes, Juan; Valdes, Sergio; Gonzalo, Montserrat; Soriguer, Federico; Moreno-Ruiz, Francisco J; Rodriguez-Cañete, Alberto; Gallego-Perales, Jose L; Alcain-Martinez, Guillermo; Vazquez-Pedreño, Luis; Lopez-Enriquez, Soledad; Garcia-Serrano, Sara; Garrido-Sanchez, Lourdes; Garcia-Fuentes, Eduardo

    2015-12-01

    The dyslipidemia associated with type 2 diabetes mellitus (T2DM) is an important risk factor for atherosclerotic cardiovascular disease. However, until now little attention has been paid to the role that the intestine might have. The aim of this research was to determine the relation between insulin resistance and intestinal de novo lipogenesis/lipoprotein synthesis in morbidly obese subjects and to study the effect of insulin on these processes. Jejunal mRNA expression of the different genes involved in the intestinal de novo lipogenesis/lipoprotein synthesis was analyzed in three groups of morbidly obese subjects: Group 1 with low insulin resistance (MO-low-IR), group 2 with high insulin resistance (MO-high-IR), and group 3 with T2DM and treatment with metformin (MO-metf-T2DM). In addition, intestinal epithelial cells (IECs) from MO-low-IR were incubated with different doses of insulin/glucose. In Group 2 (MO-high-IR), the jejunal mRNA expression levels of apo A-IV, ATP-citrate lyase (ACLY), pyruvate dehydrogenase (lipoamide) beta (PDHB), and sterol regulatory element-binding protein-1c (SREBP-1c) were significantly higher and acetyl-CoA carboxylase alpha (ACC1) and fatty-acid synthase lower than in Group 1 (MO-low-IR). In Group 3 (MO-metf-T2DM), only the ACLY and PDHB mRNA expressions were significantly higher than in Group 1 (MO-low-IR). The mRNA expression of most of the genes studied was significantly linked to insulin and glucose levels. The incubation of IEC with different doses of insulin and glucose produced a higher expression of diacylglycerol acyltransferase 2, microsomal triglyceride transfer protein, apo A-IV, SREBP-1c, and ACC1 when both, glucose and insulin, were at a high concentration. However, with only high insulin levels, there were higher apo A-IV, PDHB and SREBP-1c expressions, and a lower ACLY expression. In conclusion, the jejunum of MO-high-IR has a decreased mRNA expression of genes involved in de novo fatty-acid synthesis and an

  2. Reduction in Adiposity, β-Cell Function, Insulin Sensitivity, and Cardiovascular Risk Factors: A Prospective Study among Japanese with Obesity

    PubMed Central

    Goto, Maki; Morita, Akemi; Goto, Atsushi; Deura, Kijo; Sasaki, Satoshi; Aiba, Naomi; Shimbo, Takuro; Terauchi, Yasuo; Miyachi, Motohiko; Noda, Mitsuhiko; Watanabe, Shaw

    2013-01-01

    Background A reduction in adiposity may be associated with an improvement in insulin sensitivity and β-cell function as well as cardiovascular disease (CVD) risk factors; however, few studies have investigated these associations in a longitudinal setting. Methods To investigate these associations over a 1-year period, we conducted an observational analysis of 196 Japanese subjects with obesity in the Saku Control Obesity Program. We investigated the relations between changes in adiposity (body mass index [BMI], waist circumference, subcutaneous fat area [SFAT], and visceral fat area [VFAT]) and changes in HbA1c, fasting plasma glucose (FPG),