Science.gov

Sample records for abdominal obesity insulin

  1. Abdominal obesity, muscle composition, and insulin resistance in premenopausal women.

    PubMed

    Ross, Robert; Freeman, Jennifer; Hudson, Robert; Janssen, Ian

    2002-11-01

    The independent relationships between visceral and abdominal sc adipose tissue (AT) depots, muscle composition, and insulin sensitivity were examined in 40 abdominally obese, premenopausal women. Measurements included glucose disposal by euglycemic clamp, muscle composition by computed tomography, abdominal and nonabdominal (e.g. leg) AT by magnetic resonance imaging and cardiovascular fitness. Glucose disposal rates were negatively related to visceral AT mass (r = -0.42, P < 0.01). These observations remained significant (P < 0.01) after control for nonabdominal and abdominal sc AT, muscle attenuation, and peak oxygen uptake. Total, abdominal, or leg sc AT or muscle attenuation was not significantly (P > 0.10) related to glucose disposal. Subdivision of abdominal sc AT into anterior and posterior depots did not alter the observed relationships. Further analysis matched two groups of women for abdominal sc AT but with low and high visceral AT. Women with high visceral AT had lower glucose disposal rates compared with those with low visceral AT (P < 0.05). A similar analysis performed on two groups of women matched for visceral AT but high and low abdominal sc AT revealed no statistically different values for insulin sensitivity (P > 0.10). In conclusion, visceral AT alone is a strong correlate of insulin resistance independent of nonabdominal, abdominal sc AT, muscle composition, and cardiovascular fitness. Subdivision of abdominal sc AT did not provide additional insight into the relationship between abdominal obesity and metabolic risk.

  2. Abdominal adiposity and insulin resistance in obese men.

    PubMed

    Ross, Robert; Aru, James; Freeman, Jennifer; Hudson, Robert; Janssen, Ian

    2002-03-01

    We examined the independent relationships among various visceral and abdominal subcutaneous adipose tissue (AT) depots, glucose tolerance, and insulin sensitivity in 89 obese men. Measurements included an oral glucose tolerance test (OGTT), glucose disposal by euglycemic clamp, and abdominal and nonabdominal (e.g., peripheral) AT by magnetic resonance imaging (MRI). OGTT glucose and glucose disposal rates were related (P < 0.05) to visceral AT (r = 0.50 and -0.41, respectively). These observations remained significant (P < 0.05) after control for nonabdominal and abdominal subcutaneous AT, and maximal O(2) consumption (VO(2 max)). Abdominal subcutaneous AT was not a significant correlate (P > 0.05) of any metabolic variable after control for nonabdominal and visceral AT and VO(2 max). Division of abdominal subcutaneous AT into deep and superficial depots and visceral AT into intra- and extraperitoneal AT depots did not alter the observed relationships. Further analysis matched two groups of men for abdominal subcutaneous AT but also for low and high visceral AT. Men with high visceral AT had higher OGTT glucose values and lower glucose disposal rates compared with those with low visceral AT values (P < 0.05). A similar analysis performed on two groups of men matched for visceral AT but also for high and low abdominal subcutaneous AT revealed no statistically different values for any metabolic variable (P > 0.10). In conclusion, visceral AT alone is a strong correlate of insulin resistance independent of nonabdominal and abdominal subcutaneous AT and cardiovascular fitness. Subdivision of visceral and abdominal subcutaneous AT by MRI did not provide additional insight into the relationship between abdominal obesity and metabolic risk in obese men.

  3. 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

  4. Improvement in insulin sensitivity following a 1-year lifestyle intervention program in viscerally obese men: contribution of abdominal adiposity.

    PubMed

    Borel, Anne-Laure; Nazare, Julie-Anne; Smith, Jessica; Alméras, Natalie; Tremblay, Angelo; Bergeron, Jean; Poirier, Paul; Després, Jean-Pierre

    2012-02-01

    The objectives of the study were to quantify the effect of a 1-year healthy eating-physical activity/exercise lifestyle modification program on insulin sensitivity in viscerally obese men classified according to their glucose tolerance status and to evaluate the respective contributions of changes in body fat distribution vs changes in cardiorespiratory fitness (CRF) to the improvements in indices of plasma glucose/insulin homeostasis. Abdominally obese, dyslipidemic men (waist circumference ≥90 cm, triglycerides ≥1.69 mmol/L, and/or high-density lipoprotein cholesterol <1.03 mmol/L) were recruited. The 1-year intervention/evaluation was completed by 104 men. Body weight, composition, and fat distribution were assessed by dual-energy x-ray absorptiometry/computed tomography. Cardiorespiratory fitness and cardiometabolic risk profile were measured. After 1 year, insulin sensitivity improved in association with decreases in both visceral (VAT) and subcutaneous adiposity (SAT) as well as with the improvement in CRF, regardless of baseline glucose tolerance. Further analyses were performed according to changes in glucose tolerance status: improvement (group I, n = 39), no change (group N, n = 50), or worsening (group W, n = 15) after 1 year. Groups I and N improved their insulin sensitivity and their CRF, whereas group W did not, while losing less VAT than groups I and N. Multiple regressions showed that reduction in VAT was associated with an improvement in homeostasis model assessment of insulin resistance, whereas reduction in SAT was rather associated with improvement of the insulin sensitivity index of Matsuda. Changes in CRF were not independently associated with changes in indices of plasma glucose/insulin homeostasis. A 1-year lifestyle intervention improved plasma glucose/insulin homeostasis in viscerally obese men, including those with normal glucose tolerance status at baseline. Changes in SAT and VAT but not in CRF appeared to mediate these improvements

  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. Sagittal Abdominal Diameter to Measure Visceral Adipose Tissue in Overweight or Obese Adolescent Children and Its Role as A Marker of Insulin Resistance

    PubMed Central

    Yashoda, H.T.; Boraiah, Ganga; Vishwa, Suma

    2015-01-01

    Background Measurement of sagittal abdominal diameter using a revalidated caliper is simple, inexpensive, non-invasive method. It strongly correlates with insulin resistance and can be used as a surrogate marker to predict risk for Type II Diabetes Mellitus. Aim To assess visceral abdominal fat by measuring sagittal abdominal diameter using sliding calipers and to predict insulin resistance in obese or overweight adolescent children. Study design Explorative study for Paediatric age group among over weight and obese children aged 10-18 years in urban population in a Tertiary Care Centre. Materials and Methods Paediatric population satisfying ADA guidelines for diagnosis of prediabetes were included in the study. Anthropometric measurements with SAD were recorded. Blood was collected to investigate for prediabetes and insulin resistance using HOMA-IR. Results Out of 924 subjects who gave assent to participate in study 108 fulfilled ADA criteria. 33 subjects who didn’t come for the follow up were excluded. Out of 75 subjects 12 were detected to have insulin resistance (16%) and 63 were normal (84%). Pearson’s partial correlation of HOMA-IR and OGTT with SAD has demonstrated it to be better correlation with Insulin Resistance (IR) than other anthropometric measurements. Fasting Glucose correlated better with Waist Hip Circumference. Conclusion Insulin Resistance was diagnosed in 16% of the population and these had high levels of insulin resistance. SAD in relation to glucose metabolism, had a better correlation with OGTT followed by HOMA-IR and fasting Insulin. SAD with anthropometric measurements had better correlation all the parameters other than Waist Circumference, which had negative correlation. SAD can be used in evaluation of obese or overweight children for evaluation. PMID:26673888

  7. Partly replacing meat protein with soy protein alters insulin resistance and blood lipids in postmenopausal women with abdominal obesity.

    PubMed

    van Nielen, Monique; Feskens, Edith J M; Rietman, Annemarie; Siebelink, Els; Mensink, Marco

    2014-09-01

    Increasing protein intake and soy consumption appear to be promising approaches to prevent metabolic syndrome (MetS). However, the effect of soy consumption on insulin resistance, glucose homeostasis, and other characteristics of MetS is not frequently studied in humans. We aimed to investigate the effects of a 4-wk, strictly controlled, weight-maintaining, moderately high-protein diet rich in soy on insulin sensitivity and other cardiometabolic risk factors. We performed a randomized crossover trial of 2 4-wk diet periods in 15 postmenopausal women with abdominal obesity to test diets with 22 energy percent (En%) protein, 27 En% fat, and 50 En% carbohydrate. One diet contained protein of mixed origin (mainly meat, dairy, and bread), and the other diet partly replaced meat with soy meat analogues and soy nuts containing 30 g/d soy protein. For our primary outcome, a frequently sampled intravenous glucose tolerance test (FSIGT) was performed at the end of both periods. Plasma total, LDL, and HDL cholesterol, triglycerides, glucose, insulin, and C-reactive protein were assessed, and blood pressure, arterial stiffness, and intrahepatic lipid content were measured at the start and end of both periods. Compared with the mixed-protein diet, the soy-protein diet resulted in greater insulin sensitivity [FSIGT: insulin sensitivity, 34 ± 29 vs. 22 ± 17 (mU/L)(-1) · min(-1), P = 0.048; disposition index, 4974 ± 2543 vs. 2899 ± 1878, P = 0.038; n = 11]. Total cholesterol was 4% lower after the soy-protein diet than after the mixed-protein diet (4.9 ± 0.7 vs. 5.1 ± 0.6 mmol/L, P = 0.001), and LDL cholesterol was 9% lower (2.9 ± 0.7 vs. 3.2 ± 0.6 mmol/L, P = 0.004; n = 15). Thus, partly replacing meat with soy in a moderately high-protein diet has clear advantages regarding insulin sensitivity and total and LDL cholesterol. Therefore, partly replacing meat products with soy products could be important in preventing MetS. This trial was registered at clinicaltrials

  8. 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.

  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. 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...

  11. Dual Peroxisome Proliferator–Activated Receptor α/δ Agonist GFT505 Improves Hepatic and Peripheral Insulin Sensitivity in Abdominally Obese Subjects

    PubMed Central

    Cariou, Bertrand; Hanf, Rémy; Lambert-Porcheron, Stéphanie; Zaïr, Yassine; Sauvinet, Valérie; Noël, Benoit; Flet, Laurent; Vidal, Hubert; Staels, Bart; Laville, Martine

    2013-01-01

    OBJECTIVE The development of new insulin sensitizers is an unmet need for the treatment of type 2 diabetes. We investigated the effect of GFT505, a dual peroxisome proliferator–activated receptor (PPAR)-α/δ agonist, on peripheral and hepatic insulin sensitivity. RESEARCH DESIGN AND METHODS Twenty-two abdominally obese insulin-resistant males (homeostasis model assessment of insulin resistance >3) were randomly assigned in a randomized crossover study to subsequent 8-week treatment periods with GFT505 (80 mg/day) or placebo, followed by a two-step hyperinsulinemic-euglycemic insulin clamp with a glucose tracer to calculate endogenous glucose production (EGP). The primary end point was the improvement in glucose infusion rate (GIR). Gene expression analysis was performed on skeletal muscle biopsy specimens. RESULTS GFT505 improved peripheral insulin sensitivity, with a 21% (P = 0.048) increase of the GIR at the second insulin infusion period. GFT505 also enhanced hepatic insulin sensitivity, with a 44% (P = 0.006) increase of insulin suppression of EGP at the first insulin infusion period. Insulin-suppressed plasma free fatty acid concentrations were significantly reduced on GFT505 treatment (0.21 ± 0.07 vs. 0.27 ± 0.11 mmol/L; P = 0.006). Neither PPARα nor PPARδ target genes were induced in skeletal muscle, suggesting a liver-targeted action of GFT505. GFT505 significantly reduced fasting plasma triglycerides (−21%; P = 0.003) and LDL cholesterol (−13%; P = 0.0006), as well as liver enzyme concentrations (γ-glutamyltranspeptidase: −30.4%, P = 0.003; alanine aminotransferase: −20.5%, P = 0.004). There was no safety concern or any indication of PPARγ activation with GFT505. CONCLUSIONS The dual PPARα/δ agonist GFT505 is a liver-targeted insulin-sensitizer that is a promising drug candidate for the treatment of type 2 diabetes and nonalcoholic fatty liver disease. PMID:23715754

  12. Effects of Insulin-Like Growth Factor (IGF)-I/IGF-Binding Protein-3 Treatment on Glucose Metabolism and Fat Distribution in Human Immunodeficiency Virus-Infected Patients with Abdominal Obesity and Insulin Resistance

    PubMed Central

    Rao, Madhu N.; Mulligan, Kathleen; Tai, Viva; Wen, Michael J.; Dyachenko, Artem; Weinberg, Melissa; Li, Xiaojuan; Lang, Thomas; Grunfeld, Carl; Schwarz, Jean-Marc; Schambelan, Morris

    2010-01-01

    Context: HIV-infected patients on antiretroviral therapy are at increased risk for excess visceral adiposity and insulin resistance. Treatment with GH decreases visceral adiposity but worsens glucose metabolism. IGF-I, which mediates many of the effects of GH, improves insulin sensitivity in HIV-negative individuals. Objective: Our objective was to determine whether IGF-I, complexed to its major binding protein, IGF-binding protein-3 (IGFBP-3), improves glucose metabolism and alters body fat distribution in HIV-infected patients with abdominal obesity and insulin resistance. Methods: We conducted a pilot, open-label study in 13 HIV-infected men with excess abdominal adiposity and insulin resistance to assess the effect of 3 months of treatment with IGF-I/IGFBP-3 on glucose metabolism and fat distribution. Glucose metabolism was assessed by oral glucose tolerance test and hyperinsulinemic-euglycemic clamp. Endogenous glucose production (EGP), gluconeogenesis, whole-body lipolysis, and de novo lipogenesis (DNL) were measured with stable isotope infusions. Body composition was assessed by dual-energy x-ray absorptiometry and abdominal computed tomography scan. Results: Glucose tolerance improved and insulin-mediated glucose uptake increased significantly during treatment. EGP increased under fasting conditions, and suppression of EGP by insulin was blunted. Fasting triglycerides decreased significantly in association with a decrease in hepatic DNL. Lean body mass increased and total body fat decreased, whereas visceral adipose tissue did not change. Conclusions: Treatment with IGF-I/IGFBP-3 improved whole-body glucose uptake and glucose tolerance, while increasing hepatic glucose production. Fasting triglycerides improved, reflecting decreased DNL, and visceral adiposity was unchanged. PMID:20610601

  13. The role of antidepressants in the treatment of abdominal obesity.

    PubMed

    Rosmond, R; Björntorp, P

    2000-06-01

    The pathophysiology of abdominal obesity is unclear and controversial. Recent evidence now suggests that inadequate cortisol secretion is associated with abnormalities in glucose, insulin and lipid metabolism, including hypertension, bringing the importance of the hypothalamic-pituitary-adrenal (HPA) axis in the pathogenesis of abdominal obesity to the forefront. In addition, abnormal gonadal steroid concentrations and impaired plasma growth hormone levels accompany the abdominally obese state. Since the reproductive and growth axes are inhibited at many levels by various components of the HPA axis, increasing cortisol levels results in further depression of testosterone and growth hormone concentrations. Over the last decade, antidepressant (serotoninergic) drugs have proved useful as equalizers of HPA axis hyperactivity. Such therapy may interrupt the vicious circle of a hyperactive HPA axis leading to increasing abdominal obesity and endocrine perturbations that, in turn, leads to progressive accumulation of abdominal fat. Additionally, preliminary results indicate that serotoninergic agents decrease abdominal fat mass with improvements in related risk factors.

  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. PMID:27491154

  15. Abdominal fat and metabolic risk in obese children and adolescents.

    PubMed

    Revenga-Frauca, J; González-Gil, E M; Bueno-Lozano, G; De Miguel-Etayo, P; Velasco-Martínez, P; Rey-López, J P; Bueno-Lozano, O; Moreno, L A

    2009-12-01

    The aim of this study was to investigate fat distribution, mainly abdominal fat, and its relationship with metabolic risk variables in a group of 126 children and adolescents (60 males and 66 females) aged 5.0 to 14.9. According to IOTF criteria, 46 were classified as normal weight, 28 overweight and 52 obese. Weight, height, waist (WC) and hip circumferences were measured. The body mass index (BMI) was calculated. Total body fat, trunkal and abdominal fat were also assessed by dual energy x-ray absorptiometry (DXA). Glucose, insulin, HDL-Cholesterol, triglycerides (TG), ferritine, homocystein and C-reactive protein (CRP) were measured. Obesity status was related with insulin concentrations, CRP, TG and HDL. Obese patients had higher abdominal fat and higher CRP values than overweight and normal subjects. All markers of central body adiposity were related with insulin and lipid metabolism; however, they were not related with homocystein or ferritin. A simple anthropometric measurement, like waist circumference, seems to be a good predictor of the majority of the obesity related metabolic risk variables. PMID:20358355

  16. 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

  17. Obesity genes and insulin resistance

    PubMed Central

    Belkina, Anna C.; Denis, Gerald V.

    2011-01-01

    Purpose of review The exploding prevalence of insulin resistance and Type 2 diabetes (T2D) linked to obesity has become an alarming public health concern. Worldwide, approximately 171 million people suffer from obesity-induced diabetes and public health authorities expect this situation to deteriorate rapidly. An interesting clinical population of ‘metabolically healthy but obese’ (MHO) cases is relatively protected from T2D and its associated cardiovascular risk. The molecular basis for this protection is not well understood but is likely to involve reduced inflammatory responses. The inflammatory cells and pathways that respond to overnutrition are the primary subject matter for this review. Recent findings The chance discovery of a genetic mutation in the Brd2 gene, which is located in the class II major histocompatibility complex and makes mice enormously fat but protects them from diabetes, offers revolutionary new insights into the cellular mechanisms that link obesity to insulin resistance and T2D. These Brd2-hypomorphic mice have reduced inflammation in fat that is normally associated with insulin resistance, and resemble MHO patients, suggesting novel therapeutic pathways for obese patients at risk for T2D. Summary Deeper understanding of the functional links between genes that control inflammatory responses to diet-induced obesity is crucial to the development of therapies for obese, insulin-resistant patients. PMID:20585247

  18. 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.

  19. Abdominal obesity is an independent risk factor for increased carotid intima- media thickness in obese children.

    PubMed

    Hacihamdioğlu, Bülent; Okutan, Vedat; Yozgat, Yilmaz; Yildirim, Düzgün; Kocaoğlu, Murat; Lenk, Mustafa Koray; Ozcan, Okan

    2011-01-01

    We aimed in this study to investigate carotid intima-media thickness (IMT) in obese children and evaluate the relationship of IMT to various cardiovascular risk factors. One-hundred four obese children (9.3 +/- 2.5 years) and 30 healthy age-matched control subjects were enrolled in the study. All children were assessed for fasting levels of glucose, insulin, lipid profile, skinfold thickness (SFT), waist circumference (WC), and blood pressure (BP). Insulin resistance was estimated by the homeostasis model assessment (HOMA) index. Carotid IMT measurements and non-alcoholic fatty liver disease (NAFLD) were diagnosed with ultrasonographic findings. IMT was significantly higher in obese children compared to controls (0.49 +/- 0.05 vs. 0.40 +/- 0.02 mm, p < 0.001). Significant positive correlations were found between increased carotid IMT and body fat percentage (BFP), body mass index (BMI), age, height, systolic BP, WC, SFT, triglyceride and insulin levels, and insulin resistance index. In a linear logistic regression analysis, the only parameter affecting the increase in carotid IMT was WC (beta: 0.589, p < 0.001). Furthermore, IMT was increased significantly in obese children with NAFLD when compared to obese children without NAFLD (0.54 +/- 0.04 vs. 0.48 +/- 0.05 mm, p < 0.001). Children with abdominal obesity are at increased risk for atherosclerosis, and WC can be used to determine the atherosclerosis risk in obese children.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat.

    PubMed

    Goodpaster, B H; Thaete, F L; Simoneau, J A; Kelley, D E

    1997-10-01

    Whether visceral adipose tissue has a uniquely powerful association with insulin resistance or whether subcutaneous abdominal fat shares this link has generated controversy in the area of body composition and insulin sensitivity. An additional issue is the potential role of fat deposition within skeletal muscle and the relationship with insulin resistance. To address these matters, the current study was undertaken to measure body composition, aerobic fitness, and insulin sensitivity within a cohort of sedentary healthy men (n = 26) and women (n = 28). The subjects, who ranged from lean to obese (BMI 19.6-41.0 kg/m2), underwent dual energy X-ray absorptiometry (DEXA) to measure fat-free mass (FFM) and fat mass (FM), computed tomography to measure cross-sectional abdominal subcutaneous and visceral adipose tissue, and computed tomography (CT) of mid-thigh to measure muscle cross-sectional area, muscle attenuation, and subcutaneous fat. Insulin sensitivity was measured using the glucose clamp technique (40 mU.m-2.min-1), in conjunction with [3-3H]glucose isotope dilution. Maximal aerobic power (VO2max) was determined using an incremental cycling test. Insulin-stimulated glucose disposal (Rd) ranged from 3.03 to 16.83 mg.min-1.kg-1 FFM. Rd was negatively correlated with FM (r = -0.58), visceral fat (r = -0.52), subcutaneous abdominal fat (r = -0.61), and thigh fat (r = -0.38) and positively correlated with muscle attenuation (r = 0.48) and VO2max (r = 0.26, P < 0.05). In addition to manifesting the strongest simple correlation with insulin sensitivity, in stepwise multiple regression, subcutaneous abdominal fat retained significance after adjusting for visceral fat, while the converse was not found. Muscle attenuation contributed independent significance to multiple regression models of body composition and insulin sensitivity, and in analysis of obese subjects, muscle attenuation was the strongest single correlate of insulin resistance. In summary, as a component of

  5. Intramuscular Lipid Metabolism, Insulin Action and Obesity

    PubMed Central

    Bell, Jill A.; Houmard, Joseph A.

    2008-01-01

    Summary With the increasing prevalence of obesity, research has focused on the molecular mechanism(s) linking obesity and skeletal muscle insulin resistance. Metabolic alterations within muscle, such as changes in the cellular location of fatty acid transporter proteins, decreased mitochondrial enzyme activity and defects in mitochondrial morphology, likely contribute to obesity and insulin resistance. These defects are thought to play a role in the reduced skeletal muscle fatty acid oxidation (FAO) and increased intramuscular lipid (IMCL) accumulation that is apparent with obesity and other insulin resistant states, such as type 2 diabetes. Intramuscular triacylglycerol (IMTG) does not appear to be a ubiquitous marker of insulin resistance, although specific IMCL intermediates such as long-chain fatty acyl-CoAs (LCFA-CoAs), ceramide and diacylglycerol (DAG) may inhibit insulin signal transduction. In this review, we will briefly summarize the defects in skeletal muscle lipid metabolism associated with obesity, and discuss proposed mechanisms by which these defects may contribute to insulin resistance. PMID:18839419

  6. The Impact of Abdominal Obesity Status on Cardiovascular Response to the Mediterranean Diet

    PubMed Central

    Bédard, Alexandra; Dodin, Sylvie; Corneau, Louise; Lemieux, Simone

    2012-01-01

    We investigated the impact of abdominal obesity status on the cardiovascular response to a fully controlled 4-week isoenergetic Mediterranean diet (MedDiet). Thirty-eight abdominally obese individuals (waist circumference >102 cm in men and >88 cm in women) and thirty-one nonabdominally obese individuals were recruited and studied before and after the MedDiet. All analyses were adjusted for the slight decrease in body weight, which occurred during the MedDiet (mean: 0.9 ± 1.2 kg). A group by time interaction was noted for waist circumference (P = 0.02), abdominally obese subjects showing a significant decrease and nonabdominally obese subjects a nonsignificant increase (resp., −1.1 and +0.3%). The MedDiet resulted in decreases in total cholesterol, LDL-C, HDL-C, apolipoprotein B, A-1, and A-2, total cholesterol/HDL-C ratio, LDL-C/HDL-C ratio, and systolic and diastolic blood pressure (time effect: P < 0.05). For all variables related to glucose/insulin homeostasis, no change was observed except for a decrease in 2 h glucose concentrations (time effect: P = 0.03). No group by time interaction was observed in any of the metabolic variables studied. Results from our study suggest that the adoption of the MedDiet leads to beneficial metabolic effects, irrespective of the abdominal obesity status. PMID:23133745

  7. 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.

  8. Unsaturated Oral Fat Load Test Improves Glycemia, Insulinemia and Oxidative Stress Status in Nondiabetic Subjects with Abdominal Obesity

    PubMed Central

    Martinez-Hervas, Sergio; Navarro, Inmaculada; Real, Jose T.; Artero, Ana; Peiro, Marta; Gonzalez-Navarro, Herminia; Carmena, Rafael; Ascaso, Juan F.

    2016-01-01

    Aims To evaluate the changes in glycemia, insulinemia, and oxidative stress markers during an oral fat load test in nondiabetic subjects with abdominal obesity and to analyze the association between postprandial oxidative stress markers and postprandial glucose and insulin responses. Methods We included 20 subjects with abdominal obesity (waist circumference > 102 cm for men and > 88 cm for women) and 20 healthy lean controls (waist circumference < 102 cm for men and < 88 cm for women). After 12 hours of fasting we performed a standardized fat load test (0–8 hours) with supracal® (50 g/m2). We determined metabolic parameters, oxidized and reduced glutathione, and malondialdehyde. Results In both groups, insulin, HOMA, oxidized/reduced glutathione ratio, and malondialdehyde significantly decreased in the postprandial state after the OFLT. All these parameters were significantly higher in the abdominal obesity group at baseline and during all the postprandial points, but the reduction from the baseline levels was significantly higher in the abdominal obesity group. Conclusion Unsaturated fat improves insulin resistance and oxidative stress status. It is possible that a consumption of unsaturated fat could be beneficial even in subjects with abdominal obesity in postprandial state. PMID:27537847

  9. Obesity, insulin resistance, and microvessel density.

    PubMed

    Frisbee, Jefferson C

    2007-01-01

    The growing incidence and prevalence of the overweight/obese condition across developed economies worldwide has an enormous impact on increasing the risk for the development of impaired glycemic control or insulin resistance and ultimately peripheral vascular disease (PVD) in afflicted individuals. This places an enormous economic and social burden on these societies, in terms of additional health care costs and lost productivity and through a reduction in the quality of life of the individual owing, in part, to the progressive PVD. Characterized by an inability of the vascular systems to adequately perfuse tissues and organs relative to their metabolic demand, PVD is in part a function of a structural remodeling of the microvascular networks such that the density of microvessel and capillaries within tissues is reduced below that under normal conditions, with the potential for profound negative impacts on the processes of mass transport and exchange. The review discusses the severity of the obesity "epidemic" from the perspective of PVD and the effects of the development of the obese, insulin-resistant condition on tissue/organ microvessel density. Additional material is reviewed that addresses ameliorative treatments, primarily exercise training, on blunting microvessel loss in the obese, insulin-resistant individual, and on potential mechanistic contributors that warrant considerable future investigation.

  10. The gut microbiota, obesity and insulin resistance.

    PubMed

    Shen, Jian; Obin, Martin S; Zhao, Liping

    2013-02-01

    The human gut is densely populated by commensal and symbiotic microbes (the "gut microbiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflammation and insulin resistance. In this review we discuss molecular and cell biological mechanisms by which the microbiota participate in host functions that impact the development and maintenance of the obese state, including host ingestive behavior, energy harvest, energy expenditure and fat storage. We additionally explore the diverse signaling pathways that regulate gut permeability and bacterial translocation to the host and how these are altered in the obese state to promote the systemic inflammation ("metabolic endotoxemia") that is a hallmark of obesity and its complications. Fundamental to our discussions is the concept of "crosstalk", i.e., the biochemical exchange between host and microbiota that maintains the metabolic health of the superorganism and whose dysregulation is a hallmark of the obese state. Differences in community composition, functional genes and metabolic activities of the gut microbiota appear to distinguish lean vs obese individuals, suggesting that gut 'dysbiosis' contributes to the development of obesity and/or its complications. The current challenge is to determine the relative importance of obesity-associated compositional and functional changes in the microbiota and to identify the relevant taxa and functional gene modules that promote leanness and metabolic health. As diet appears to play a predominant role in shaping the microbiota and promoting obesity-associated dysbiosis, parallel initiatives are required to elucidate dietary patterns and diet components (e.g., prebiotics, probiotics) that promote healthy gut microbiota. How the microbiota promotes human health and disease is a rich area of investigation that is likely to generate

  11. Cardiovascular Disease Risk of Abdominal Obesity versus Metabolic Abnormalities

    PubMed Central

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

    2011-01-01

    It remains unclear whether abdominal obesity increases cardiovascular disease (CVD) risk independent of the metabolic abnormalities which often accompany it. Therefore, the objective of the current study was to evaluate the independent effects of abdominal obesity versus metabolic syndrome and diabetes on the risk for incident coronary heart disease 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) versus metabolic syndrome (excluding the waist circumference criterion) and diabetes on risk for incident coronary heart disease and stroke in 20,298 men and women aged ≥45 years. The average follow-up was 8.3 (standard deviation 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 [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. PMID:20725064

  12. 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.

  13. Central obesity, type 2 diabetes and insulin: exploring a pathway full of thorns

    PubMed Central

    Papakyriakou, Panagiotis; Panagiotou, Themistoklis N.

    2015-01-01

    The prevalence of type 2 diabetes (T2D) is rapidly increasing. This is strongly related to the contemporary lifestyle changes that have resulted in increased rates of overweight individuals and obesity. Central (intra-abdominal) obesity is observed in the majority of patients with T2D. It is associated with insulin resistance, mainly at the level of skeletal muscle, adipose tissue and liver. The discovery of macrophage infiltration in the abdominal adipose tissue and the unbalanced production of adipocyte cytokines (adipokines) was an essential step towards novel research perspectives for a better understanding of the molecular mechanisms governing the development of insulin resistance. Furthermore, in an obese state, the increased cellular uptake of non-esterified fatty acids is exacerbated without any subsequent β-oxidation. This in turn contributes to the accumulation of intermediate lipid metabolites that cause defects in the insulin signaling pathway. This paper examines the possible cellular mechanisms that connect central obesity with defects in the insulin pathway. It discusses the discrepancies observed from studies organized in cell cultures, animal models and humans. Finally, it emphasizes the need for therapeutic strategies in order to achieve weight reduction in overweight and obese patients with T2D. PMID:26170839

  14. Adipose cell size in obese Africans: evidence against the existence of insulin resistance in some patients.

    PubMed

    Joffe, B I; Goldberg, R B; Feinstein, J; Kark, A; Seftel, H C

    1979-05-01

    Aspects of adipose tissue cellularity were examined in 15 non-diabetic premenopausal African women with simple obesity living in Johannesburg. A smaller group of six non-obese Black women served as controls. Adipose tissue was obtained by biopsy from the deltoid, gluteal, and abdominal regions, and the mean fat cell size for each site was determined. Fasting plasma glucose, insulin, and lipid levels, and the glucose and insulin responses to a 100 g oral glucose load, in these subjects provided metabolic data for correlative analyses. As expected, the overall mean and regional adipocyte sizes were significantly larger in the overweight subjects. Significant regional variations in fat cell size were also seen, the gluteal region adipocytes being larger than those of other sites in both obese and non-obese women. A significant positive correlation was found between fat cell size and the percentage of ideal body weight. There was no significant relationship between adipocyte size, however, and any of the metabolic variables measured--notably basal or stimulated plasma insulin. Nearly half of the overweight women showed large adipocytes with normal plasma insulin concentrations. A proportion of African women with hypertrophic obesity do not appear to demonstrate any classical metabolic features of insulin resistance; this may be related partly to their high carbohydrate intake and unusual degree of physical activity. Our results do not, however, indicate that hyperinsulinaemia is completely absent in obese Black women.

  15. Predictive models of insulin resistance derived from simple morphometric and biochemical indices related to obesity and the metabolic syndrome in baboons

    PubMed Central

    Chavez, Alberto O; Gastaldelli, Amalia; Guardado-Mendoza, Rodolfo; Lopez-Alvarenga, Juan C; Leland, M Michelle; Tejero, M Elizabeth; Sorice, GianPio; Casiraghi, Francesca; Davalli, Alberto; Bastarrachea, Raúl A; Comuzzie, Anthony G; DeFronzo, Ralph A; Folli, Franco

    2009-01-01

    Background Non-human primates are valuable models for the study of insulin resistance and human obesity. In baboons, insulin sensitivity levels can be evaluated directly with the euglycemic clamp and is highly predicted by adiposity, metabolic markers of obesity and impaired glucose metabolism (i.e. percent body fat by DXA and HbA1c). However, a simple method to screen and identify obese insulin resistant baboons for inclusion in interventional studies is not available. Methods We studied a population of twenty baboons with the euglycemic clamp technique to characterize a population of obese nondiabetic, insulin resistant baboons, and used a multivariate linear regression analysis (adjusted for gender) to test different predictive models of insulin sensitivity (insulin-stimulated glucose uptake = Rd) using abdominal circumference and fasting plasma insulin. Alternatively, we tested in a separate baboon population (n = 159), a simpler model based on body weight and fasting plasma glucose to predict the whole-body insulin sensitivity (Rd/SSPI) derived from the clamp. Results In the first model, abdominal circumference explained 59% of total insulin mediated glucose uptake (Rd). A second model, which included fasting plasma insulin (log transformed) and abdominal circumference, explained 64% of Rd. Finally, the model using body weight and fasting plasma glucose explained 51% of Rd/SSPI. Interestingly, we found that percent body fat was directly correlated with the adipocyte insulin resistance index (r = 0.755, p < 0.0001). Conclusion In baboons, simple morphometric measurements of adiposity/obesity, (i.e. abdominal circumference), plus baseline markers of glucose/lipid metabolism, (i.e. fasting plasma glucose and insulin) provide a feasible method to screen and identify overweight/obese insulin resistant baboons for inclusion in interventional studies aimed to study human obesity, insulin resistance and type 2 diabetes mellitus. PMID:19389241

  16. Relationship of obesity and insulin resistance with the cerebrovascular reactivity: a case control study

    PubMed Central

    2014-01-01

    Background Obesity is associated with increased risk for stroke. The breath-holding index (BHI) is a measure of vasomotor reactivity of the brain which can be measured with the transcranial Doppler (TCD). We aim to evaluate obesity as an independent factor for altered cerebrovascular reactivity. Methods Cerebrovascular hemodynamics (mean flow velocities MFV, pulsatility index, PI, resistance index, RI, and BHI) was determined in 85 non-obese (Body Mass Index, BMI ≤27 kg/m2) and 85 obese subjects (BMI ≥35 kg/m2) without diabetes mellitus and hypertension. Anthropometric and metabolic variables, and scores to detect risk for obstructive sleep apnea (OSA) were analyzed for their association with the cerebrovascular reactivity. Results The BHI was significantly lower in subjects with obesity according to BMI and in subjects with abdominal obesity, but the PI and RI were not different between groups. There was a linear association between the BMI, the HOMA-IR, the Matsuda index, the waist circumference, and the neck circumference, with the cerebrovascular reactivity. After adjusting for insulin resistance, neck circumference, and abdominal circumference, obesity according to BMI was negatively correlated with the cerebrovascular reactivity. Conclusions We found a diminished vasomotor reactivity in individuals with obesity which was not explained by the presence of insulin resistance. PMID:24383894

  17. Synergic insulin sensitizing effect of rimonabant and BGP-15 in Zucker-obese rats.

    PubMed

    Literati-Nagy, Zsuzsanna; Tory, Kálmán; Literáti-Nagy, Botond; Bajza, Agnes; Vígh, László; Vígh, László; Mandl, József; Szilvássy, Zoltán

    2013-07-01

    Abdominal obesity is referred for as a common pathogenic root of multiple risk factors, which include insulin resistance, dyslipidemia, hypertension, and a pro-atherogenic and pro-inflammatory state. Irrespective of its psychiatric side effects, rimonabant through blocking cannabinoid-1 receptor (CB1R) induces an increase in whole body insulin sensitivity. The aim of this work was to study the effect of selected doses of another insulin sensitizer compound BGP-15, and rimonabant on insulin resistance in Zucker obese rats with a promise of inducing insulin sensitization together at lower doses than would have been expected by rimonabant alone. We found that BGP-15 potentiates the insulin sensitizing effect of rimonabant. The combination at doses, which do not induce insulin sensitization by themselves, improved insulin signaling. Furthermore our results suggest that capsaicin-induced signal may play a role in insulin sensitizing effect of both molecules. Our data might indicate that a lower dose of rimonabant in the treatment of insulin resistance and type 2 diabetes is sufficient to administer, thus a lower incidence of the unfavorable psychiatric side effects of rimonabant are to be expected.

  18. Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance.

    PubMed

    Saad, M J A; Santos, A; Prada, P O

    2016-07-01

    Obesity and insulin resistance are the major predisposing factors to comorbidities, such as Type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases, and several types of cancer. The prevalence of obesity is still increasing worldwide and now affects a large number of individuals. Here, we review the role of the gut microbiota in the pathophysiology of insulin resistance/obesity. The human intestine is colonized by ∼100 trillion bacteria, which constitute the gut microbiota. Studies have shown that lean and overweight rodents and humans may present differences in the composition of their intestinal flora. Over the past 10 years, data from different sources have established a causal link between the intestinal microbiota and obesity/insulin resistance. It is important to emphasize that diet-induced obesity promotes insulin resistance by mechanisms independent and dependent on gut microbiota. In this review, we present several mechanisms that contribute to explaining the link between intestinal flora and insulin resistance/obesity. The LPS from intestinal flora bacteria can induce a chronic subclinical inflammatory process and obesity, leading to insulin resistance through activation of TLR4. The reduction in circulating SCFA may also have an essential role in the installation of reduced insulin sensitivity and obesity. Other mechanisms include effects of bile acids, branched-chain amino acids (BCAA), and some other lesser-known factors. In the near future, this area should open new therapeutic avenues for obesity/insulin resistance and its comorbidities. PMID:27252163

  19. Gender differences of regional abdominal fat distribution and their relationships with insulin sensitivity in healthy and glucose-intolerant Thais.

    PubMed

    Rattarasarn, Chatchalit; Leelawattana, Rattana; Soonthornpun, Supamai; Setasuban, Worawong; Thamprasit, Atchara

    2004-12-01

    To determine gender differences of regional abdominal fat distribution and their relationships with insulin sensitivity in healthy and glucose-intolerant Thais, 44 subjects, 22 men and 22 body mass index-matched women, with normal and abnormal glucose tolerance, which included subjects with impaired glucose tolerance and diabetes, were studied. Total body fat and total abdominal fat (TAF) at L1-L4 were measured by dual-energy x-ray absorptiometry. Regional abdominal fat, which consists of sc abdominal fat and visceral abdominal fat, was determined by single-slice computerized tomography of the abdomen at L4-L5 disc space level. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp and expressed as glucose infusion rate (GIR). With comparable body mass index, visceral abdominal fat was most strongly correlated with GIR after adjustment with percent total body fat in both healthy (r = -0.8155; P = 0.007) and glucose-intolerant women (r = -0.7597; P = 0.011), whereas TAF was most strongly correlated with GIR in both healthy (r = -0.8114; P = 0.008) and glucose-intolerant men (r = -0.6194; P = 0.101). By linear regression analysis, visceral abdominal fat accounted for 35.0% (beta = -3.53 x 10(-2); P = 0.001) of GIR variance in women, whereas TAF accounted for 39.3% (beta = -1.28 x 10(-4); P < 0.0001) of GIR variance in men. We conclude that there are gender differences in the relationships of regional abdominal fat and insulin sensitivity in slightly obese healthy and glucose-intolerant Thais, the difference of which may possibly be in part due to the difference of abdominal fat patterning between genders.

  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. Relationship of internalized racism to abdominal obesity and blood pressure in Afro-Caribbean women.

    PubMed

    Tull, S E; Wickramasuriya, T; Taylor, J; Smith-Burns, V; Brown, M; Champagnie, G; Daye, K; Donaldson, K; Solomon, N; Walker, S; Fraser, H; Jordan, O W

    1999-08-01

    Racism is associated with increased psychosocial stress and blood pressure in blacks. However, little is known of the relationship of racism to other features of insulin resistance syndrome. This study examined the relationship of internalized racism to abdominal obesity and elevated blood pressure in a population of black Caribbean women aged 20-55 years. One hundred thirty-three randomly selected women from the island of Barbados comprised the study sample. Data collected included anthropometric and blood pressure measurements, and information about internalized racism, anxiety, and depression. The stress measures including anxiety, depression, and internalized racism were significantly correlated with waist circumference (r = .25, r = .21, and r = .25). After adjusting for age, education, anxiety, and depression, internalized racism remained significantly correlated with waist circumference. The odds ratio associated with development of abdominal obesity among those with high internalized racism (OR = 2.4 [95% CI, 1.1,5.3]) was significant (P < .05) after adjusting for age, education, and body mass index. Blood pressure was not independently related to internalized racism. Studies comparing black-white differences in diseases for which abdominal obesity is a risk factor (eg, diabetes and cardiovascular disease) should take into account the potential role of internalized racism in defining the differences between ethnic groups.

  2. Impact of hypertension, overall obesity and abdominal obesity on diabetes incidence in Shanghai residents with different glucose levels.

    PubMed

    Qian, Qiaohui; Li, Xu; Feng, Bo

    2012-06-01

    The impact of hypertension, overall obesity and abdominal obesity, individually or collectively, on diabetes incidence over a period of 5 years in residents with different glucose levels is diverse, with abdominal obesity having an impact in both non-diabetic hyperglycaemia and normal groups.

  3. 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

  4. Dysregulation of the Peripheral and Adipose Tissue Endocannabinoid System in Human Abdominal Obesity

    PubMed Central

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

    2008-01-01

    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 (CB1) 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, CB1 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. PMID:17065342

  5. 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

    2014-08-01

    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.

  6. 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

    2014-08-01

    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. PMID:25100064

  7. The Adipose Transcriptional Response to Insulin Is Determined by Obesity, Not Insulin Sensitivity.

    PubMed

    Rydén, Mikael; Hrydziuszko, Olga; Mileti, Enrichetta; Raman, Amitha; Bornholdt, Jette; Boyd, Mette; Toft, Eva; Qvist, Veronica; Näslund, Erik; Thorell, Anders; Andersson, Daniel P; Dahlman, Ingrid; Gao, Hui; Sandelin, Albin; Daub, Carsten O; Arner, Peter

    2016-08-30

    Metabolically healthy obese subjects display preserved insulin sensitivity and a beneficial white adipose tissue gene expression pattern. However, this observation stems from fasting studies when insulin levels are low. We investigated adipose gene expression by 5'Cap-mRNA sequencing in 17 healthy non-obese (NO), 21 insulin-sensitive severely obese (ISO), and 30 insulin-resistant severely obese (IRO) subjects, before and 2 hr into a hyperinsulinemic euglycemic clamp. ISO and IRO subjects displayed a clear but globally similar transcriptional response to insulin, which differed from the small effects observed in NO subjects. In the obese, 231 genes were altered; 71 were enriched in ISO subjects (e.g., phosphorylation processes), and 52 were enriched in IRO subjects (e.g., cellular stimuli). Common cardio-metabolic risk factors and gender do not influence these findings. This study demonstrates that differences in the acute transcriptional response to insulin are primarily driven by obesity per se, challenging the notion of healthy obese adipose tissue, at least in severe obesity. PMID:27545890

  8. [Comparison of biosynthetic human insulin and purified pork insulin. Studies in insulin-resistant obese patients using the insulin suppression test].

    PubMed

    Richard, J L; Rodier, M; Cavalie, G; Lachkar, H; Orsetti, A; Monnier, L; Mirouze, J

    1986-02-01

    An insulin suppression test performed in random order with either biosynthetic human insulin or purified pork insulin was used to compare biological activity of these two insulins in obese patients suffering from varying degrees of glucose intolerance. Blood glucose curve, steady-state blood glucose levels, insulin sensitivity indices and steady-state plasma insulin levels were identical during the two sets of tests. Furthermore endogenous insulin and glucagon secretion were similarly suppressed. The insulin suppression test is a simple and rapid procedure to compare the biological activity of fast-acting insulins. Our results confirm the insulin-resistance in obesity and clearly show that biosynthetic human and porcine insulins have similar biological potency.

  9. ADRB2 haplotype is associated with glucose tolerance and insulin sensitivity in obese postmenopausal women.

    PubMed

    Prior, Steven J; Goldberg, Andrew P; Ryan, Alice S

    2011-02-01

    The β(2)-adrenergic receptor (ADRB2) mediates obesity, cardiorespiratory fitness, and insulin resistance. We examined the hypothesis that ADRB2 Arg16Gly-Gln27Glu haplotype is associated with body composition, glucose tolerance, and insulin sensitivity in obese, postmenopausal women. Obese (>35% body fat), postmenopausal (age 45-75 years) women (n = 123) underwent genotyping, dual-energy X-ray absorptiometry, and computed tomography scans, exercise testing (VO(2(max))), 2-h oral glucose tolerance tests (OGTTs), and hyperinsulinemic-euglycemic clamps (80 mU/m(2)/min). Analysis of covariance (ANCOVA) tested for differences among haplotypes, with race, % body fat, and VO(2(max)) as covariates. We found that ADRB2 haplotype was independently associated with % body fat, abdominal fat distribution, VO(2(max)), insulin sensitivity (M/ΔInsulin), and glucose tolerance (ANOVA, P < 0.05 for all). Women homozygous for Gly16-Gln27 haplotype had the highest % body fat (52.7 ± 1.9%), high abdominal fat, low M/ΔInsulin (0.49 ± 0.08 mg/kg/min/pmol/l/10(2)), and impaired glucose tolerance (IGT) during an OGTT (G(120) = 10.2 ± 0.9 mmol/l). Women homozygous for Gly16-Glu27 haplotype also had low M/ΔInsulin (0.51 ± 0.05 mg/kg/min/pmol/l/10(2)) and IGT (G(120) = 8.2 ± 0.7 mmol/l). Subjects with Arg16-Gln27/Gly16-Gln27 haplotype combination had the highest VO(2(max)) (1.84 ± 0.07 l/min) and M/ΔInsulin (0.7 ± 0.04 mg/kg/min/pmol/l/10(2)), and normal glucose tolerance (G(120) = 6.4 ± 0.4 mmol/l), despite being obese. These data show associations of the ADRB2 Arg16Gly-Gln27Glu haplotype with VO(2(max)) and body composition, and an independent association with glucose metabolism, which persists after controlling for body composition and fitness. This suggests that ADRB2 haplotypes may mediate insulin action, glucose tolerance, and potentially risk for type 2 diabetes mellitus (T2DM) in obese, postmenopausal women.

  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. Relation of abdominal obesity to hyperinsulinemia and high blood pressure in men.

    PubMed

    Johnson, D; Prud'homme, D; Després, J P; Nadeau, A; Tremblay, A; Bouchard, C

    1992-11-01

    The relationships between body fatness, adipose tissue distribution, plasma glucose, insulin levels, lipoprotein levels, and resting blood pressure were studied in 81 men aged 36.0 +/- 3.3 years (mean +/- s.d.) (body mass index (BMI): 27.4 +/- 3.8 kg/m2, percentage body fat: 26.4 +/- 6.6%). Systolic and diastolic blood pressures (BP) were significantly associated with the BMI (r = 0.31, r = 0.33, P < 0.01), the waist circumference (r = 0.33, r = 0.27; P < 0.01) as well as with adipose tissue areas measured by computerized tomography (CT) (0.27 < or = r < or = 0.36, P < 0.01). Furthermore, the relative accumulation of subcutaneous abdominal fat, as estimated by the ratio of abdominal to femoral adipose tissue areas measured by CT, was positively correlated with systolic and diastolic BP (P < 0.01). Fasting plasma insulin level (r = 0.30, P < 0.01) as well as the insulin area measured during an oral glucose tolerance test (0.34 < or = r < or = 0.37, P < 0.01) were significantly correlated with blood pressure. Systolic and diastolic BP were significantly associated with HDL2-cholesterol (C) as well as with the HDL2-C/HDL3-C ratio (-0.24 < or = r < or = -0.34), whereas triglycerides (r = 0.23) and the HDL-C/C ratio (r = -0.23) were significantly correlated with diastolic BP only (P < 0.05). Multivariate analysis indicated that the insulin area was the most important variable associated with blood pressure and that this association was independent of total body fatness and regional adipose tissue distribution. Plasma insulin levels explained 14% and 11% of the variance observed in the systolic and diastolic blood pressures respectively. These results suggest that most of the association between abdominal obesity and high blood pressure is mediated by the hyperinsulinemia and/or the related insulin resistant state.

  12. 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

  13. Insulin and blood pressure during weight loss in obese adolescents.

    PubMed

    Rocchini, A P; Katch, V; Schork, A; Kelch, R P

    1987-09-01

    The role of insulin in the regulation of blood pressure was evaluated in 50 obese adolescents before and after a 20-week weight loss program. When compared with 10 nonobese adolescents, the obese subjects had significantly higher systolic, diastolic, and mean arterial pressures (p = 0.005), an elevated 24-hour urinary sodium excretion (p = 0.002), an elevated fasting insulin concentration (p = 0.001), and an abnormal insulin response to an oral glucose tolerance test (sum of the insulins at 0, 1, and 2 hours post-oral glucose load; p = 0.001). We also observed a significant correlation between systolic and diastolic blood pressure (age and sex normalized) and body weight (r = 0.57, p less than 0.01 and r = 0.7, p less than 0.01), fasting insulin (r = 0.49, p less than 0.01 and r = 0.54, p less than 0.01), and sum of insulins (r = 0.42, p less than 0.01 and r = 0.46, p less than 0.01). To study the effect of weight loss on the relationship between blood pressure and insulin, the obese subjects were randomly assigned to three groups: 15 to a diet and behavior change group, 18 to a diet, behavior change, and exercise group, and 17 to an obese control group. Compared with the obese control group, the two weight loss groups each experienced a significant decrease in insulin (p less than 0.01), sum of the insulins (p less than 0.01), and blood pressure (p less than 0.01). The decrease in blood pressure during the weight loss program significantly correlated with the change in both insulin and body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

  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. Evidence in Obese Children: Contribution of Hyperlipidemia, Obesity-Inflammation, and Insulin Sensitivity

    PubMed Central

    Chang, Chi-Jen; Jian, Deng-Yuan; Lin, Ming-Wei; Zhao, Jun-Zhi; Ho, Low-Tone; Juan, Chi-Chang

    2015-01-01

    Background Evidence shows a high incidence of insulin resistance, inflammation and dyslipidemia in adult obesity. The aim of this study was to assess the relevance of inflammatory markers, circulating lipids, and insulin sensitivity in overweight/obese children. Methods We enrolled 45 male children (aged 6 to 13 years, lean control = 16, obese = 19, overweight = 10) in this study. The plasma total cholesterol, HDL cholesterol, triglyceride, glucose and insulin levels, the circulating levels of inflammatory factors, such as TNF-α, IL-6, and MCP-1, and the high-sensitive CRP level were determined using quantitative colorimetric sandwich ELISA kits. Results Compared with the lean control subjects, the obese subjects had obvious insulin resistance, abnormal lipid profiles, and low-grade inflammation. The overweight subjects only exhibited significant insulin resistance and low-grade inflammation. Both TNF-α and leptin levels were higher in the overweight/obese subjects. A concurrent correlation analysis showed that body mass index (BMI) percentile and fasting insulin were positively correlated with insulin resistance, lipid profiles, and inflammatory markers but negatively correlated with adiponectin. A factor analysis identified three domains that explained 74.08% of the total variance among the obese children (factor 1: lipid, 46.05%; factor 2: obesity-inflammation, 15.38%; factor 3: insulin sensitivity domains, 12.65%). Conclusions Our findings suggest that lipid, obesity-inflammation, and insulin sensitivity domains predominantly exist among obese children. These factors might be applied to predict the outcomes of cardiovascular diseases in the future. PMID:26011530

  16. Inhibition of 11β-hydroxysteroid dehydrogenase type 1 ameliorates obesity-related insulin resistance.

    PubMed

    Shao, Shiying; Zhang, Xiaojie; Zhang, Muxun

    2016-09-01

    Excess 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) may be implicated in the development of obesity related metabolic disorders. The present study measured the expression level of 11β-HSD1 in visceral adipose tissues from 23 patients undergoing abdominal operation. Correlation of 11β-HSD1 expression with BMI, waist-to-hip ratio (WHR), HOMA-IR, and serum lipids was evaluated by spearman correlation analysis. High-fat diet-induced obese (DIO) rats were orally dosed with BVT.2733 for 4 weeks. Weight, plasma insulin, and lipids were detected at the end of the treatment. The effects of 11β-HSD1 inhibition on the key insulin-signaling cascade and adipocytokines were measured by western blot and ELISA respectively. 11β-HSD1 was increased in patients with central obesity, the expression level of which was closely related with WHR (r = 0.5851), BMI (r = 0.4952), and HOMA-IR (r = 0.4637). Obesity related insulin resistance in high-fat DIO rats, as reflected by a marked decrease in IRS-1, IRS-2, GLUT4, and PI3K, could be attenuated by 11β-HSD1 inhibition. Furthermore, the down-regulation of 11β-HSD1 could correct the disordered profiles of adipocytokines including adiponectin, IL-6, and TNF-α. These findings indicated that 11β-HSD1 inhibition can give a potential benefit in reducing obesity and lowering insulin resistance by modulating the insulin-signaling pathway and adipocytokine production. PMID:27268236

  17. Metabolic inflexibility and insulin resistance in obese adolescents with nonalcoholic fatty liver disease

    PubMed Central

    Lee, SoJung; Rivera-Vega, Michelle; Alsayed, Hany Mohamed Abdel Aal; Boesch, Chris; Libman, Ingrid

    2014-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) is a comorbidity of childhood obesity. Objective We examined whole-body substrate metabolism and metabolic characteristics in obese adolescents with versus without NAFLD. Subjects Twelve obese (BMI≥95th) adolescents with and without NAFLD [intrahepatic triglyceride (IHTG) ≥5.0 % versus <5.0 %] were pair-matched for race, gender, age and % body fat. Methods Insulin sensitivity (IS) was assessed by a 3-hour hyperinsulinemic-euglycemic clamp and whole-body substrate oxidation by indirect calorimetry during fasting and insulin-stimulated conditions. Results Adolescents with NAFLD had increased (P<0.05) abdominal fat, lipids and liver enzymes compared with those without NAFLD. Fasting glucose concentration was not different between groups, but fasting insulin concentration was higher (P<0.05) in the NAFLD group compared with those without. Fasting hepatic glucose production and hepatic IS did not differ (P>0.1) between groups. Adolescents with NAFLD had higher (P<0.05) fasting glucose oxidation and a tendency for lower fat oxidation. Adolescents with NAFLD had lower (P<0.05) insulin-stimulated glucose disposal and lower peripheral IS compared with those without NAFLD. Although RQ increased significantly from fasting to insulin-stimulated conditions in both groups (main effect, P<0.001), the increase in RQ was lower in adolescents with NAFLD versus those without (interaction, P=0.037). Conclusion NAFLD in obese adolescents is associated with adverse cardiometabolic profile, peripheral insulin resistance and metabolic inflexibility. PMID:24754380

  18. The expression of ob gene is not acutely regulated by insulin and fasting in human abdominal subcutaneous adipose tissue.

    PubMed

    Vidal, H; Auboeuf, D; De Vos, P; Staels, B; Riou, J P; Auwerx, J; Laville, M

    1996-07-15

    The regulation of ob gene expression in abdominal subcutaneous adipose tissue was investigated using a reverse transcription-competitive PCR method to quantify the mRNA level of leptin. Leptin mRNA level was highly correlated with the body mass index of 26 subjects (12 lean, 7 non-insulin-dependent diabetic, and 7 obese patients). The effect of fasting on ob gene expression was investigated in 10 subjects maintained on a hypocaloric diet (1045 KJ/d) for 5 d. While their metabolic parameters significantly changed (decrease in insulinemia, glycemia, and resting metabolic rate and increase in plasma ketone bodies), the caloric restriction did not modify the leptin mRNA level in the adipose tissue. To verify whether insulin regulates ob gene expression, six lean subjects underwent a 3-h euglycemic hyperinsulinemic (846 +/- 138 pmol/liter) clamp. Leptin and Glut 4 mRNA levels were quantified in adipose tissue biopsies taken before and at the end of the clamp. Insulin infusion produced a significant threefold increase in Glut 4 mRNA while leptin mRNA was not affected. It is concluded that ob gene expression is not acutely regulated by insulin or by metabolic factors related to fasting in human abdominal subcutaneous adipose tissue. PMID:8755631

  19. Insulin sensitive and resistant obesity in humans: AMPK activity, oxidative stress, and depot-specific changes in gene expression in adipose tissue[S

    PubMed Central

    Xu, X. Julia; Gauthier, Marie-Soleil; Hess, Donald T.; Apovian, Caroline M.; Cacicedo, Jose M.; Gokce, Noyan; Farb, Melissa; Valentine, Rudy J.; Ruderman, Neil B.

    2012-01-01

    We previously reported that adenosine monophosphate-activated protein kinase (AMPK) activity is lower in adipose tissue of morbidly obese individuals who are insulin resistant than in comparably obese people who are insulin sensitive. However, the number of patients and parameters studied were small. Here, we compared abdominal subcutaneous, epiploic, and omental fat from 16 morbidly obese individuals classified as insulin sensitive or insulin resistant based on the homeostatic model assessment of insulin resistance. We confirmed that AMPK activity is diminished in the insulin resistant group. A custom PCR array revealed increases in mRNA levels of a wide variety of genes associated with inflammation and decreases in PGC-1α and Nampt in omental fat of the insulin resistant group. In contrast, subcutaneous abdominal fat of the same patients showed increases in PTP-1b, VEGFa, IFNγ, PAI-1, and NOS-2 not observed in omental fat. Only angiotensinogen and CD4+ mRNA levels were increased in both depots. Surprisingly, TNFα was only increased in epiploic fat, which otherwise showed very few changes. Protein carbonyl levels, a measure of oxidative stress, were increased in all depots. Thus, adipose tissues of markedly obese insulin resistant individuals uniformly show decreased AMPK activity and increased oxidative stress compared with insulin sensitive patients. However, most changes in gene expression appear to be depot-specific. PMID:22323564

  20. Influence of acute aerobic exercise on adiponectin oligomer concentrations in middle-aged abdominally obese men.

    PubMed

    Numao, Shigeharu; Katayama, Yasutomi; Hayashi, Yoichi; Matsuo, Tomoaki; Tanaka, Kiyoji

    2011-02-01

    Exercise intensity may induce changes in total adiponectin and adiponectin oligomer levels. However, the effects of acute aerobic exercise on total adiponectin and adiponectin oligomers in middle-aged abdominally obese men remain unknown. The purpose of this study was to investigate the influence of aerobic exercise intensity on changes in the concentrations of total adiponectin and adiponectin oligomers (high-molecular weight [HMW] and middle- plus low-molecular weight [MLMW] adiponectin), and the endocrine mechanisms involved in exercise-induced changes in adiponectin oligomer profiles in middle-aged abdominally obese men. Using a crossover design, 9 middle-aged abdominally obese men (age, 54.1 ± 2.4 years; body mass index, 27.9 ± 0.6 kg/m²) underwent 2 trials that consisted of 60 minutes of stationary cycle exercise at either moderate-intensity (ME) or high-intensity (HE) aerobic exercise (50% or 70% of peak oxygen uptake, respectively). Blood samples were collected to measure the concentrations of adiponectin oligomers, hormones (catecholamines, insulin, and growth hormone), metabolites (free fatty acid, glycerol, triglyceride, and glucose), and cytokines (interleukin-6 and tumor necrosis factor-α). After exercise, plasma catecholamine concentrations were higher during HE than during ME (P < .05). Total adiponectin concentration decreased at the end of HE (P < .05), but remained unchanged after ME. The HMW adiponectin concentration did not change at either intensity, whereas the MLMW concentration decreased at the end of HE (P < .05). The ratio of HMW to total adiponectin concentration increased significantly (P < .05), whereas the ratio of MLMW to total adiponectin concentration decreased significantly (P < .05), at the end of HE. The percentage changes in epinephrine concentration from baseline to the end of exercise were correlated with the percentage changes in total adiponectin concentration (r = -0.67, P < .05) and MLMW adiponectin concentration (r

  1. 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.

  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. 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

  4. 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

  5. Vitamin D insufficiency and insulin resistance in obese adolescents.

    PubMed

    Peterson, Catherine A; Tosh, Aneesh K; Belenchia, Anthony M

    2014-12-01

    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

  6. 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

  7. Obesity, insulin resistance, and skeletal muscle nitric oxide synthase

    PubMed Central

    Kraus, Raymond M.; Houmard, Joseph A.; Kraus, William E.; Tanner, Charles J.; Pierce, Joseph R.; Choi, Myung Dong

    2012-01-01

    The molecular mechanisms responsible for impaired insulin action have yet to be fully identified. Rodent models demonstrate a strong relationship between insulin resistance and an elevation in skeletal muscle inducible nitric oxide synthase (iNOS) expression; the purpose of this investigation was to explore this potential relationship in humans. Sedentary men and women were recruited to participate (means ± SE: nonobese, body mass index = 25.5 ± 0.3 kg/m2, n = 13; obese, body mass index = 36.6 ± 0.4 kg/m2, n = 14). Insulin sensitivity was measured using an intravenous glucose tolerance test with the subsequent modeling of an insulin sensitivity index (SI). Skeletal muscle was obtained from the vastus lateralis, and iNOS, endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) content were determined by Western blot. SI was significantly lower in the obese compared with the nonobese group (∼43%; P < 0.05), yet skeletal muscle iNOS protein expression was not different between nonobese and obese groups. Skeletal muscle eNOS protein was significantly higher in the nonobese than the obese group, and skeletal muscle nNOS protein tended to be higher (P = 0.054) in the obese compared with the nonobese group. Alternative analysis based on SI (high and low tertile) indicated that the most insulin-resistant group did not have significantly more skeletal muscle iNOS protein than the most insulin-sensitive group. In conclusion, human insulin resistance does not appear to be associated with an elevation in skeletal muscle iNOS protein in middle-aged individuals under fasting conditions. PMID:22797309

  8. 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

  9. [Overweight and abdominal obesity in adults in aquilombocommunity in Bahia State, Brazil].

    PubMed

    Soares, Daniela Arruda; Barreto, Sandhi Maria

    2014-02-01

    This study analyzes nutritional status, estimates the prevalence of overweight and abdominal obesity, and investigates factors associated with these outcomes in a two-stage random sample of adults (> 20 years) in quilombos (communities that descend from African slaves) in Vitória da Conquista, Bahia State, Brazil, in 2011. Among 739 participants, prevalence rates were 31.8% and 10.2% for overweight and obesity, respectively, and 55.7% for increased waist-to-height ratio (> 0.50). Prevalence of overweight was higher among 30-39-year-olds, while abdominal obesity was more frequent among older individuals. Female sex, eating chicken or beef with untrimmed fat, and hypertension were associated with higher odds of overweight and abdominal obesity, while smoking and single marital status were associated with lower odds. The results show high prevalence rates for overweight and abdominal obesity in these very poor and socially isolated communities. Specific preventive and control measures are urgently needed.

  10. Distribution of abdominal obesity and fitness level in overweight and obese korean adults.

    PubMed

    Kim, Sue; Kim, Ji-Young; Lee, Duk-Chul; Lee, Hye-Sun; Lee, Ji-Won; Jeon, Justin Y

    2014-01-01

    Background. Abdominal obesity and its relative distribution are known to differ in association with metabolic characteristics and cardiorespiratory fitness. This study aimed to determine an association between fitness level and abdominal adiposity in overweight and obese adults. Methods. 228 overweight and obese individuals were classified as either cardiorespiratory unfit or fit based on their recovery heart rate. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), the visceral-to-subcutaneous adipose tissue ratio (VAT/SAT ratio), and cardiometabolic characteristics were analyzed to examine the relationship between recovery heart rate and abdominal adiposity components. Results. After adjustments for age and sex, significant relationships of recovery heart rate and VAT, SAT, and VAT/SAT ratio were found; however, SAT was not significantly associated after further adjustment for body mass index (BMI) (r = 0.045, P = 0.499), whereas VAT (r = 0.232, P < 0.001) and VAT/SAT ratio (r = 0.214, P = 0.001) remained associated. Through stepwise multiple regression analyses after adjustment for age, sex, BMI, lifestyle factors, mean blood pressure, fasting glucose, HOMA-IR, lipid profiles, and hsCRP, recovery heart rate was identified as an independent variable associated with VAT (β = 0.204, P < 0.001) and VAT/SAT ratio (β = 0.163, P = 0.008) but not with SAT (β = 0.097, P = 0.111). Conclusions. Cardiorespiratory fitness level is independently associated with VAT and the VAT/SAT ratio but not with SAT in overweight and obese adults. PMID:24723950

  11. [Childhhood obesity, insulin resistance and increased cardiovascular risk].

    PubMed

    Carlone, Angela; Venditti, Chiara; Cipolloni, Laura; Zampetti, Simona; Spoletini, Marialuisa; Capizzi, Marco; Leto, Gaetano; Buzzetti, Raffaella

    2012-10-01

    Excess fat is one of the major risk factors for insulin resistance predisposing to the development of cardiovascular diseases in western countries. We know that obese patients are strongly at risk of cardiovascular diseases, like myocardial infarction or stroke. These diseases are the most frequent cause of death in the adult population, representing a social and economic problem. Today there are not available and useful markers for screening and diagnosis of insulin- resistance in young people. "Easy-to-detect" clinical markers must be found to identify young subjects at risk of cardiovascular diseases. Very interesting the relationship between wrist circumference, its bone composition and insulin resistance. PMID:23114400

  12. 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

  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. 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.

  15. 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. PMID:20795429

  16. 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…

  17. Impaired insulin-mediated antilipolysis and lactate release in adipose tissue of upper-body obese women.

    PubMed

    Nellemann, Birgitte; Gormsen, Lars C; Sørensen, Lars P; Christiansen, Jens S; Nielsen, Søren

    2012-01-01

    Upper-body/visceral obesity is associated with abnormalities of free fatty acid (FFA) metabolism and greater risk of developing type 2 diabetes compared with lower-body obesity. In lean subjects lipolysis is readily suppressed by insulin; however, metabolic inflexibility with respect to antilipolysis is a frequent finding in obesity, partly determined by body composition. This study investigates effects of insulin on regional adipose tissue lipolysis and lactate levels in upper-body overweight/obese (UBO), lower-body overweight/obese (LBO), and lean women. The microdialysis technique was used to assess adipose tissue glycerol and lactate concentrations in abdominal and femoral fat during a 5-h basal period and a 2-h hyperinsulinemic euglycemic clamp. The main findings were that the antilipolytic effect of insulin was attenuated in abdominal fat of UBO (glycerol reduction, abd (%): UBO 40.4 (-14 to 66), LBO 46.0 (-8 to 66), lean 66.2 (2-78), ANOVA, P < 0.05), and in femoral fat in both obese groups (glycerol reduction, fem (%): UBO 44.4 (35-67), LBO 44.4 (0-63), lean 65.0 (43-79), ANOVA, P < 0.05). Further, abdominal fat insulin-mediated increase in lactate concentration was greater in lean women compared with UBO women (lactate increase, abd (%): UBO -6.1 (-37.1 to 57.4), LBO 16.5 (-32.2 to 112.5), lean 51.4 (-45.7 to 162.9), P < 0.05), whereas no differences were found between groups in femoral fat (lactate increase, fem (%), UBO -12.9 (-43 to 24), LBO 12.7 (-30.7 to 92), lean 27.6 (-9.5 to 123.8), not significant). Respiratory exchange ratio (RER) increased significantly and similarly in all groups. So, UBO women were metabolically inflexible with respect to insulins antilipolytic and lactate increasing effects in abdominal adipose tissue. These phenomena are probably both consequences of insulin resistance of adipose tissue. PMID:21959346

  18. 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.

  19. 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

  20. Abdominal obesity and chronic stress interact to predict blunted cardiovascular reactivity.

    PubMed

    Singh, Kulwinder; Shen, Biing-Jiun

    2013-10-01

    Abdominal obesity and chronic stress have independent effects on cardiac autonomic regulation, and may also interact to influence cardiovascular reactivity. In addition to main effects, we hypothesized that abdominal obesity and chronic stress would interact and predict blunted cardiovascular reactivity. One hundred and twenty-two undergraduate students engaged in two stressful laboratory tasks while cardiovascular activity was assessed. Results indicated that higher abdominal obesity significantly predicted blunted systolic blood pressure (SBP) and mean arterial pressure (MAP) change, while chronic stress was not directly associated with any measure of cardiovascular reactivity. Furthermore, there was a significant interaction between abdominal obesity and chronic stress on SBP and MAP change such that among participants with higher chronic stress, higher abdominal obesity was significantly associated with reduced SBP and MAP reactivity. In addition, body-mass index (BMI), a measure of overall obesity, also had both main and interaction effects with chronic stress to predict blunted cardiovascular reactivity. These results suggest that abdominally obese individuals may incur difficulty in mounting appropriately-sized cardiovascular responses during acute stress, particularly when under high levels of chronic stress.

  1. 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.

  2. Skeletal Muscle Insulin Resistance and Absence of Inflammation Characterize Insulin-Resistant Grade I Obese Women

    PubMed Central

    Bourret, Annick; Lambert, Karen; Birot, Olivier; Fédou, Christine; Dupuy, Anne-Marie; Cristol, Jean-Paul; Sutra, Thibault; Molinari, Nicolas; Maimoun, Laurent; Mariano-Goulart, Denis; Galtier, Florence; Avignon, Antoine; Stanke-Labesque, Françoise; Mercier, Jacques; Sultan, Ariane; Bisbal, Catherine

    2016-01-01

    Context Obesity is associated with insulin-resistance (IR), the key feature of type 2 diabetes. Although chronic low-grade inflammation has been identified as a central effector of IR development, it has never been investigated simultaneously at systemic level and locally in skeletal muscle and adipose tissue in obese humans characterized for their insulin sensitivity. Objectives We compared metabolic parameters and inflammation at systemic and tissue levels in normal-weight and obese subjects with different insulin sensitivity to better understand the mechanisms involved in IR development. Methods 30 post-menopausal women were classified as normal-weight insulin-sensitive (controls, CT) and obese (grade I) insulin-sensitive (OIS) or insulin-resistant (OIR) according to their body mass index and homeostasis model assessment of IR index. They underwent a hyperinsulinemic-euglycemic clamp, blood sampling, skeletal muscle and subcutaneous adipose tissue biopsies, an activity questionnaire and a self-administrated dietary recall. We analyzed insulin sensitivity, inflammation and IR-related parameters at the systemic level. In tissues, insulin response was assessed by P-Akt/Akt expression and inflammation by macrophage infiltration as well as cytokines and IκBα expression. Results Systemic levels of lipids, adipokines, inflammatory cytokines, and lipopolysaccharides were equivalent between OIS and OIR subjects. In subcutaneous adipose tissue, the number of anti-inflammatory macrophages was higher in OIR than in CT and OIS and was associated with higher IL-6 level. Insulin induced Akt phosphorylation to the same extent in CT, OIS and OIR. In skeletal muscle, we could not detect any inflammation even though IκBα expression was lower in OIR compared to CT. However, while P-Akt/Akt level increased following insulin stimulation in CT and OIS, it remained unchanged in OIR. Conclusion Our results show that systemic IR occurs without any change in systemic and tissues

  3. Duration of Abdominal Obesity Beginning in Young Adulthood and Incident Diabetes Through Middle Age

    PubMed Central

    Reis, Jared P.; Hankinson, Arlene L.; Loria, Catherine M.; Lewis, Cora E.; Powell-Wiley, Tiffany; Wei, Gina S.; Liu, Kiang

    2013-01-01

    OBJECTIVE To examine whether the duration of abdominal obesity determined prospectively using measured waist circumference (WC) is associated with the development of new-onset diabetes independent of the degree of abdominal adiposity. RESEARCH DESIGN AND METHODS The Coronary Artery Risk Development in Young Adults Study is a multicenter, community-based, longitudinal cohort study of 5,115 white and black adults aged 18–30 years in 1985 to 1986. Years spent abdominally obese were calculated for participants without abdominal obesity (WC >102 cm in men and >88 cm in women) or diabetes at baseline (n = 4,092) and was based upon repeat measurements conducted 2, 5, 7, 10, 15, 20, and 25 years later. RESULTS Over 25 years, 392 participants developed incident diabetes. Overall, following adjustment for demographics, family history of diabetes, study center, and time varying WC, energy intake, physical activity, smoking, and alcohol, each additional year of abdominal obesity was associated with a 4% higher risk of developing diabetes [hazard ratio (HR) 1.04 (95% CI 1.02–1.07)]. However, a quadratic model best represented the data. HRs for 0, 1–5, 6–10, 11–15, 16–20, and >20 years of abdominal obesity were 1.00 (referent), 2.06 (1.43–2.98), 3.45 (2.28–5.22), 3.43 (2.28–5.22), 2.80 (1.73–4.54), and 2.91 (1.60–5.29), respectively; P-quadratic < 0.001. CONCLUSIONS Longer duration of abdominal obesity was associated with substantially higher risk for diabetes independent of the degree of abdominal adiposity. Preventing or at least delaying the onset of abdominal obesity in young adulthood may lower the risk of developing diabetes through middle age. PMID:23248193

  4. Alveolar recruitment maneuver and perioperative ventilatory support in obese patients undergoing abdominal surgery

    PubMed Central

    Forgiarini Júnior, Luiz Alberto; Rezende, Juliana Castilhos; Forgiarini, Soraia Genebra Ibrahim

    2013-01-01

    The development of abdominal surgery represents an alternative therapy for the morbidly obese; however, patients undergoing this surgical procedure often experience postoperative pulmonary complications. The use of alveolar recruitment maneuvers and/or perioperative ventilatory strategies is a possible alternative to reduce these complications, focusing on the reduction of postoperative pulmonary complications. In this review, the benefits of perioperative ventilatory strategies and the implementation of alveolar recruitment maneuvers in obese patients undergoing abdominal surgery are described. PMID:24553513

  5. 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

  6. Abdominal Obesity Indicators: Waist Circumference or Waist-to-hip Ratio in Malaysian Adults Population

    PubMed Central

    Ahmad, Norfazilah; Adam, Samia Ibrahim Mohamed; Nawi, Azmawati Mohammed; Hassan, Mohd Rohaizat; Ghazi, Hasanain Faisal

    2016-01-01

    Background: Waist circumference (WC) is an accurate and simple measure of abdominal obesity as compared to waist–hip ratio (WHR). The aim of this study was to determine the correlation between body mass index (BMI) with WC and WHR and suggest cutoff points for WC among Rural Malaysian adults. Methods: A cross-sectional study was conducted among 669 respondents from three villages in Tanjung Karang, located in the district of Kuala Selangor. Data collection was carried out by guided questionnaires and anthropometric measures. Results: The prevalence of abdominal obesity for BMI was almost similar for both gender across Caucasian and Asian BMI cutoff points. Based on Caucasian cutoff points, the prevalence of abdominal obesity for WC was 23.8% (male) and 66.4% (female) while for WHR was 6.2% (male) and 54.2% (female). Asian cutoff points gave higher prevalence of abdominal obesity compared to that of WC among male respondents and WHR for both genders. WC showed strong and positive correlation with BMI compared to WHR (in male WC r = 0.78, WHR r = 0.24 and in female WC r = 0.72, WHR r = 0.19; P < 0.001). Receiver operating characteristic curve analysis suggested WC cutoff points of 92.5 cm in men and 85.5 cm in women is the optimal number for detection of abdominal obesity. Conclusions: WC is the best indicator as compared with WHR for abdominal obesity for Malaysian adults. PMID:27330688

  7. 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. PMID:26833850

  8. 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.

  9. 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

  10. 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.

  11. RISK FACTORS FOR ABDOMINAL OBESITY IN CHILDREN AND ADOLESCENTS FROM CRACOW, POLAND (1983-2000).

    PubMed

    Suder, Agnieszka; Chrzanowska, Maria

    2015-03-01

    The aim of this study was to determine abdominal obesity risk factors in two successive cohorts of children and adolescents aged 4-18 from Cracow, Poland, examined during the years of political transformation. The influence of biological, socio-demographic and lifestyle factors on abdominal obesity was analysed by calculating odds ratios and 95% confidence intervals using logistic regression analysis. It was found that for girls obesity in both parents (OR=4.31; 95% CI 1.73-20.70) and high birth weight (OR=1.78; 95% CI 1.12-2.82) were significant risk factors for abdominal obesity in the 1983 cohort. In the 2000 cohort obesity in both parents for boys and girls (boys: OR=5.85; 95% CI 1.36-25.10; girls: OR=4.82; 95% CI 1.17-19.77), low level of parental education in girls (OR=2.06; 95% CI 1.15-3.69), having only one son (OR=1.96; 95% CI 1.36-3.40), parents' smoking habits in girls (OR=2.94; 95% CI 1.46-5.91) and lack of undertaking physical activity in sport clubs in boys (OR=6.11; 95% CI 1.46-25.47) were significant abdominal obesity risk factors. Higher number of hours of leisure time physical activity (OR=0.89; 95% CI 0.81-0.97) significantly lowered the risk of abdominal obesity in boys in the 2000 cohort. The greater differentiation of abdominal obesity risk factors in the 2000 cohort in comparison to the 1983 cohort may have resulted from the social and economic changes taking place in Poland at the end of the 20th century.

  12. Mechanisms of insulin resistance in human obesity: evidence for receptor and postreceptor defects.

    PubMed Central

    Kolterman, O G; Insel, J; Saekow, M; Olefsky, J M

    1980-01-01

    To assess the mechanisms of the insulin resistance in human obesity, we have determined, using a modification of the euglycemic glucose clamp technique, the shape of the in vivo insulin-glucose disposal dose-response curves in 7 control and 13 obese human subjects. Each subject had at least three euglycemic studies performed at insulin infusion rates of 15, 40, 120, 240, or 1,200 mU/M2/min. The glucose disposal rate was decreased in all obese subjects compared with controls (101 +/- 16 vs. 186 +/- 16 mg/M2/min) during the 40 mU/M2/min insulin infusion. The mean dose-response curve for the obese subjects was displaced to the right, i.e., the half-maximally effective insulin concentration was 270 +/- 27 microU/ml for the obese compared with 130 +/- 10 microU/ml for controls. In nine of the obese subjects, the dose-response curves were shifted to the right, and maximal glucose disposal rates (at a maximally effective insulin concentration) were markedly decreased, indicating both a receptor and a postreceptor defect. On the other hand, four obese patients had right-shifted dose-response curves but reached normal maximal glucose disposal rates, consistent with decreased insulin receptors as the only abnormality. When the individual data were analyzed, it was found that the lease hyperinsulinemic, least insulin-resistant patients displayed only the receptor defect, whereas those with the greatest hyperinsulinemia exhibited the largest post-receptor defect, suggesting a continuous spectrum of defects as one advances from mild to severe insulin resistance. When insulin's ability to suppress hepatic glucose output was assessed, hyperinsulinemia produced total suppresssion in all subjects. The dose-response curve for the obese subjects was shifted to the right, indicating a defect in insulin receptors. Insulin binding to isolated adipocytes obtained from the obese subjects was decreased, and a highly significant inverse linear relationship was demonstrated between insulin

  13. Do obese but metabolically normal women differ in intra-abdominal fat and physical activity levels from those with the expected metabolic abnormalities? A cross-sectional study

    PubMed Central

    2010-01-01

    Background Obesity remains a major public health problem, associated with a cluster of metabolic abnormalities. However, individuals exist who are very obese but have normal metabolic parameters. The aim of this study was to determine to what extent differences in metabolic health in very obese women are explained by differences in body fat distribution, insulin resistance and level of physical activity. Methods This was a cross-sectional pilot study of 39 obese women (age: 28-64 yrs, BMI: 31-67 kg/m2) recruited from community settings. Women were defined as 'metabolically normal' on the basis of blood glucose, lipids and blood pressure. Magnetic Resonance Imaging was used to determine body fat distribution. Detailed lifestyle and metabolic profiles of participants were obtained. Results Women with a healthy metabolic profile had lower intra-abdominal fat volume (geometric mean 4.78 l [95% CIs 3.99-5.73] vs 6.96 l [5.82-8.32]) and less insulin resistance (HOMA 3.41 [2.62-4.44] vs 6.67 [5.02-8.86]) than those with an abnormality. The groups did not differ in abdominal subcutaneous fat volume (19.6 l [16.9-22.7] vs 20.6 [17.6-23.9]). A higher proportion of those with a healthy compared to a less healthy metabolic profile met current physical activity guidelines (70% [95% CIs 55.8-84.2] vs 25% [11.6-38.4]). Intra-abdominal fat, insulin resistance and physical activity make independent contributions to metabolic status in very obese women, but explain only around a third of the variance. Conclusion A sub-group of women exists who are metabolically normal despite being very obese. Differences in fat distribution, insulin resistance, and physical activity level are associated with metabolic differences in these women, but account only partially for these differences. Future work should focus on strategies to identify those obese individuals most at risk of the negative metabolic consequences of obesity and on identifying other factors that contribute to metabolic status

  14. Cardiorespiratory Fitness and Insulin Sensitivity in Overweight or Obese Subjects May Be Linked Through Intrahepatic Lipid Content

    PubMed Central

    Haufe, Sven; Engeli, Stefan; Budziarek, Petra; Utz, Wolfgang; Schulz-Menger, Jeanette; Hermsdorf, Mario; Wiesner, Susanne; Otto, Christoph; Haas, Verena; de Greiff, Armin; Luft, Friedrich C.; Boschmann, Michael; Jordan, Jens

    2010-01-01

    OBJECTIVE Low cardiorespiratory fitness (CRF) predisposes one to cardiovascular disease and type 2 diabetes in part independently of body weight. Given the close relationship between intrahepatic lipid content (IHL) and insulin sensitivity, we hypothesized that the direct relationship between fitness and insulin sensitivity may be explained by IHL. RESEARCH DESIGN AND METHODS We included 138 overweight to obese, otherwise healthy subjects (aged 43.6 ± 8.9 years, BMI 33.8 ± 4 kg/m2). Body composition was estimated by bioimpedance analyses. Abdominal fat distribution, intramyocellular, and IHL were assessed by magnetic resonance spectroscopy and tomography. Incremental exercise testing was performed to estimate an individual's CRF. Insulin sensitivity was determined during an oral glucose tolerance test. RESULTS For all subjects, CRF was related to insulin sensitivity (r = 0.32, P < 0.05), IHL (r = −0.27, P < 0.05), and visceral (r = −0.25, P < 0.05) and total fat mass (r = −0.32, P < 0.05), but not to intramyocellular lipids (r = −0.08, NS). Insulin sensitivity correlated significantly with all fat depots. In multivariate regression analyses, independent predictors of insulin sensitivity were IHL, visceral fat, and fitness (r2 = −0.43, P < 0.01, r2 = −0.34, and r2 = 0.29, P < 0.05, respectively). However, the positive correlation between fitness and insulin sensitivity was abolished after adjustment for IHL (r = 0.16, NS), whereas it remained significant when adjusted for visceral or total body fat. Further, when subjects were grouped into high versus low IHL, insulin sensitivity was higher in those subjects with low IHL, irrespective of fitness levels. CONCLUSIONS Our study suggests that the positive effect of increased CRF on insulin sensitivity in overweight to obese subjects may be mediated indirectly through IHL reduction. PMID:20357364

  15. 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.

  16. 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. PMID:24064339

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

    PubMed

    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.

  18. Independent effects of obesity and insulin resistance on postprandial thermogenesis in men.

    PubMed Central

    Segal, K R; Albu, J; Chun, A; Edano, A; Legaspi, B; Pi-Sunyer, F X

    1992-01-01

    The putative blunted thermogenesis in obesity may be related to insulin resistance, but insulin sensitivity and obesity are potentially confounding factors. To determine the independent effects of obesity and insulin resistance on the thermic effect of food, at rest and after exercise, lean and obese men were matched at two levels of insulin sensitivity determined by insulin-stimulated glucose disposal (milligrams per kilogram fat-free mass [FFM] per minute) during the euglycemic, hyperinsulinemic (40 mU/m2.min) clamp: 5.4 mg/kg FFM for the lean and obese groups with low insulin sensitivity, and 8.1 mg/kg FFM for the groups with high insulin sensitivity. The two lean groups were matched for percent fat (approximately 15 +/- 1% fat), as were the two obese groups (approximately 33 +/- 2% fat). Energy expenditure was measured for 3 h in the fasting state and for 3 h after a 720-kcal mixed meal, each at rest and immediately after 1 h of cycling at 100 W. The thermic effect of food (TEF) was calculated as the postprandial minus fasting energy expenditure (kcal/3 h) during rest and after exercise. During rest, TEF was blunted by both obesity (24 +/- 5 and 34 +/- 6 kcal/3 h for obese groups with low and high insulin sensitivity vs. 56 +/- 6 and 74 +/- 6 kcal/3 h for the lean groups with low and high insulin sensitivity; P less than 0.01 lean vs. obese) and insulin resistance (insulin-resistant less than insulin-sensitive, at both levels of obesity; P less than 0.01). After exercise, TEF was also impaired in the obese (47 +/- 6 and 44 +/- 5 kcal/3 h for the insulin-resistant and -sensitive groups) and in the lean insulin-resistant (55 +/- 5 kcal/3 h), compared with the lean insulin-sensitive men (71 +/- 3 kcal/3 h), P less than 0.01. Compared with rest, TEF after exercise was improved, but not normalized, in both obese groups (P less than 0.05), but unchanged in the lean groups. These results suggest that both insulin resistance and obesity are independently associated

  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. 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

  1. Mildly compromised tetrahydrobiopterin cofactor biosynthesis due to Pts variants leads to unusual body fat distribution and abdominal obesity in mice.

    PubMed

    Korner, Germaine; Scherer, Tanja; Adamsen, Dea; Rebuffat, Alexander; Crabtree, Mark; Rassi, Anahita; Scavelli, Rossana; Homma, Daigo; Ledermann, Birgit; Konrad, Daniel; Ichinose, Hiroshi; Wolfrum, Christian; Horsch, Marion; Rathkolb, Birgit; Klingenspor, Martin; Beckers, Johannes; Wolf, Eckhard; Gailus-Durner, Valérie; Fuchs, Helmut; Hrabě de Angelis, Martin; Blau, Nenad; Rozman, Jan; Thöny, Beat

    2016-03-01

    Tetrahydrobiopterin (BH4) is an essential cofactor for the aromatic amino acid hydroxylases, alkylglycerol monooxygenase, and nitric oxide synthases (NOS). Inborn errors of BH4 metabolism lead to severe insufficiency of brain monoamine neurotransmitters while augmentation of BH4 by supplementation or stimulation of its biosynthesis is thought to ameliorate endothelial NOS (eNOS) dysfunction, to protect from (cardio-) vascular disease and/or prevent obesity and development of the metabolic syndrome. We have previously reported that homozygous knock-out mice for the 6-pyruvolytetrahydropterin synthase (PTPS; Pts-ko/ko) mice with no BH4 biosynthesis die after birth. Here we generated a Pts-knock-in (Pts-ki) allele expressing the murine PTPS-p.Arg15Cys with low residual activity (15% of wild-type in vitro) and investigated homozygous (Pts-ki/ki) and compound heterozygous (Pts-ki/ko) mutants. All mice showed normal viability and depending on the severity of the Pts alleles exhibited up to 90% reduction of PTPS activity concomitant with neopterin elevation and mild reduction of total biopterin while blood L-phenylalanine and brain monoamine neurotransmitters were unaffected. Yet, adult mutant mice with compromised PTPS activity (i.e., Pts-ki/ko, Pts-ki/ki or Pts-ko/wt) had increased body weight and elevated intra-abdominal fat. Comprehensive phenotyping of Pts-ki/ki mice revealed alterations in energy metabolism with proportionally higher fat content but lower lean mass, and increased blood glucose and cholesterol. Transcriptome analysis indicated changes in glucose and lipid metabolism. Furthermore, differentially expressed genes associated with obesity, weight loss, hepatic steatosis, and insulin sensitivity were consistent with the observed phenotypic alterations. We conclude that reduced PTPS activity concomitant with mildly compromised BH4-biosynthesis leads to abnormal body fat distribution and abdominal obesity at least in mice. This study associates a novel

  2. The relationships between intra-abdominal echogenicity, cardiometabolic risk factors and physical performance in obese children.

    PubMed

    Yoo, Ji Won; Lee, Nam-Gi; Kim, Hee-Jung; Cho, Hyo-Min; You, Joshua H

    2014-01-01

    While the abdominal adipose tissue has been identified as an important pathomarker for the cardiometabolic syndrome in adults, the relationships between the cardiometabolic risk factors and abdominal adipose morphology or physical performance levels have not been examined in children with obesity. Therefore, the specific aim of this study was to investigate the relationships between risk factors (BMI and physical activity levels and abdominal fat layers including subcutaneous, intra-abdominal preperitoneal and mesenteric fat thickness in children with obesity. 30 children with obesity (mean ± SD = 10.0 ± 4.5 yrs; 9 girls; BMI > 20) underwent physical performance (curl-ups, sit and reach, push-ups, and a 400-m run), ultrasound measurement of thickness of fat composition of the abdomen, blood pressure, oxygen consumption. Pearson correlation analysis showed significant correlations, ranging from -0.523- 0.898 between the intra-abdominal adipose tissue thickness, cardiometabolic risk factors (BMI, blood pressure, heart rate), and the curl-up physical performance test. In conclusion, the present study provides a compelling evidence that the intra-abdominal adipose tissue morphological characteristics were associated with BMI, physical performance, and most importantly cardiometabolic risk factors (blood pressure and heart rate), which eventually contribute to the development of cardiometabolic syndrome in adulthood.

  3. [Rational therapy of patients with essential hypertension and abdominal obesity with concomitant subclinical hypothyroidism].

    PubMed

    Pligovka, V M

    2014-11-01

    It was determined the characteristics of lipid status of patients with essential hypertension, abdominal obesity with concomitant subclinical hypothyroidism--mostly increased levels of total and LDL cholesterol. In assessing the effectiveness of statin therapy in combination with levothyroxine replacement therapy compared with statin monotherapy, combination therapy showed the best result in terms of achievement of target levels of both total cholesterol and LDL. The obtained results allow us to recommend the use of combination therapy for patients with hypertension, abdominal obesity with concomitant subclinical hypothyroidism in order to achieve the target values of LDL and thus to reduce the cardiovascular risk of these patients.

  4. Abdominal wall pain in obese women: frequently missed and easily treated

    PubMed Central

    Mishriki, Yehia Yousri

    2009-01-01

    Chronic abdominal pain is a common symptom with an extensive differential diagnosis. The work-up is frequently costly, yet many patients elude definitive diagnosis. We describe 12 obese women with long-standing abdominal pain, many of whom eluded diagnosis but who met criteria for abdominal wall pain. Each patient underwent a focused history and physical examination which included checking for Carnett’s sign and performing a “pinch test”. All patients had positive Carnett’s sign and pinch tests. An injection of local anaesthetic, with or without corticosteroid, completely relieved the pain within 10 min. Of the six patients seen in follow-up, four remained pain free and two responded to a second injection of local anaesthetic. Abdominal wall pain is an under-appreciated cause of chronic abdominal pain. Diagnosis is often straightforward and treatment with a local injection of anaesthetic is both diagnostic and curative. PMID:21686788

  5. 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

  6. Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats

    PubMed Central

    2011-01-01

    Background Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Methods Monosodium glutamate (MSG) (4 mg/g body weight) was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C), coconut fat-treated normal weight group (CO), fish oil-treated normal weight group (FO), obese control group (Ob), coconut fat-treated obese group (ObCO) and fish oil-treated obese group (ObFO). Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day) for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. Results Obese animals (Ob) presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt) showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO) similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30%) and triacylglycerol (TG; 33%) compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. Conclusions Low dose of fish oil supplementation (1 g/kg/day) was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms. PMID:21526994

  7. 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...

  8. Nobiletin improves obesity and insulin resistance in high-fat diet-induced obese mice.

    PubMed

    Lee, Young-Sil; Cha, Byung-Yoon; Choi, Sun-Sil; Choi, Bong-Keun; Yonezawa, Takayuki; Teruya, Toshiaki; Nagai, Kazuo; Woo, Je-Tae

    2013-01-01

    Nobiletin (NOB) is a polymethoxylated flavone present in citrus fruits and has been reported to have antitumor and anti-inflammatory effects. However, little is known about the effects of NOB on obesity and insulin resistance. In this study, we examined the effects of NOB on obesity and insulin resistance, and the underlying mechanisms, in high-fat diet (HFD)-induced obese mice. Obese mice were fed a HFD for 8 weeks and then treated without (HFD control group) or with NOB at 10 or 100mg/kg. NOB decreased body weight gain, white adipose tissue (WAT) weight and plasma triglyceride. Plasma glucose levels tended to decrease compared with the HFD group and improved plasma adiponectin levels and glucose tolerance. Furthermore, NOB altered the expression levels of several lipid metabolism-related and adipokine genes. NOB increased the mRNA expression of peroxisome proliferator-activated receptor (PPAR)-γ, sterol regulatory element-binding protein-1c, fatty acid synthase, stearoyl-CoA desaturase-1, PPAR-α, carnitine palmitoyltransferase-1, uncoupling protein-2 and adiponectin, and decreased the mRNA expression of tumor necrosis factor-α and monocyte chemoattractant protein-1 in WAT. NOB also up-regulated glucose transporter-4 protein expression and Akt phosphorylation and suppressed IκBα degradation in WAT. Taken together, these results suggest that NOB improves adiposity, dyslipidemia, hyperglycemia and insulin resistance. These effects may be elicited by regulating the expression of lipid metabolism-related and adipokine genes, and by regulating the expression of inflammatory makers and activity of the insulin signaling pathway.

  9. 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

  10. Associations of breaks in sedentary time with abdominal obesity in Portuguese older adults.

    PubMed

    Júdice, Pedro B; Silva, Analiza M; Santos, Diana A; Baptista, Fátima; Sardinha, Luís B

    2015-01-01

    In older adults, sedentary time is positively associated with obesity. The manner in which it is accumulated, i.e., the number of breaks in sedentary time, might be also important. We examined the cross-sectional associations of breaks in sedentary time with abdominal obesity in 301 older adults (111 men and 190 women) aged 75.0 ± 6.8 years. Sedentary time (counts min(-1) < 100) and physical activity were objectively measured by accelerometry, worn during waking hours for at least three consecutive days. A break was defined as an interruption (≥ 100 counts min(-1) < 2020) in sedentary time while performing light intensity physical activities. Sedentary time was expressed as the number of daily breaks in sedentary time or hourly breaks in sedentary time. Abdominal obesity was defined by waist circumference (men >102 cm; women >88 cm). Using binary logistic regression analyses, the odds for abdominal obesity decreased 7 % for each additional hourly break in sedentary time in women (OR = 0.93, 95 % CI: 0.87-1.00), but not men, independently of total sedentary time and moderate-to-vigorous physical activity. The odds for abdominal obesity were 3.21 times higher (p = 0.039) for women in quartile 1 (<225 breaks day(-1)) of daily breaks in sedentary time compared to those in quartile 4 (>353 breaks day(-1)) of daily breaks in sedentary time.These findings indicate that older women who interrupt their sedentary time more frequently are less likely to present abdominal obesity. Public health recommendations regarding breaking-up sedentary time complementary to those for physical activity are likely to be relevant.

  11. Impact of obesity and insulin-resistance on cirrhosis and portal hypertension.

    PubMed

    Berzigotti, Annalisa; Abraldes, Juan G

    2013-10-01

    Obesity is sharply rising worldwide and is increasingly recognized in patients with cirrhosis. This review summarizes the available data documenting a detrimental role of obesity and insulin-resistance on the risk of appearance of clinical events in patients with cirrhosis. Molecular pathways explaining the harmful effect of obesity and insulin resistance in the natural history of cirrhosis are largely unknown. Increasing knowledge of mechanisms leading to white adipose tissue dysfunction on one side, and to portal hypertension on the other side, allow hypothesizing that a link between the pathophysiology of obesity, insulin resistance and portal hypertension in cirrhosis exists. Mechanisms likely involved in this interplay are discussed in this article.

  12. Exercise in aging: its important role in mortality, obesity and insulin resistance

    PubMed Central

    Ryan, Alice S

    2011-01-01

    The prevalence of overweight and obesity has increased dramatically over the last several decades. Obesity and physical inactivity increase the risk for cardiovascular disease, Type 2 diabetes mellitus, hypertension, dyslipidemia and certain cancers. Obesity and low levels of physical fitness are also associated with increased risk of all-cause and cardiovascular mortality. Central and total obesity, insulin resistance and inactivity increase with age. Exercise training and increased fitness promote positive changes in body composition and improve insulin sensitivity. This article will describe the effects of exercise training, both aerobic and resistive, on body composition and obesity as well as review studies investigating the effects of exercise training on glucose metabolism and insulin sensitivity in older adults. Adopting a physically active lifestyle should be emphasized in overweight and obese individuals with insulin resistance to reduce the risk for cardiovascular events in the aging population. PMID:21359160

  13. Altered insulin response to an acute bout of exercise in pediatric obesity.

    PubMed

    Tran, Brian D; Leu, Szu-Yun; Oliver, Stacy; Graf, Scott; Vigil, Diana; Galassetti, Pietro

    2014-11-01

    Pediatric obesity typically induces insulin resistance, often later evolving into type 2 diabetes. While exercise, enhancing insulin sensitivity, is broadly used to prevent this transition, it is unknown whether alterations in the exercise insulin response pattern occur in obese children. Therefore, we measured exercise insulin responses in 57 healthy weight (NW), 20 overweight (OW), and 56 obese (Ob) children. Blood samples were drawn before and after 30 min of intermittent (2 min on, 1 min off) cycling at ~80% VO2max. In a smaller group (14 NW, 6 OW, 15 Ob), a high-fat meal was ingested 45 min preexercise. Baseline glycemia was similar and increased slightly and similarly in all groups during exercise. Basal insulin (pmol/L) was significantly higher in Ob vs. other groups; postexercise, insulin increased in NW (+7± 3) and OW (+5 ± 8), but decreased in Ob (-15±5, p < .0167 vs. NW). This insulin drop in Ob was disproportionately more pronounced in the half of Ob children with higher basal insulin (Ob-H). In all groups, high-fat feeding caused a rapid rise in insulin, promptly corrected by exercise. In Ob, however, insulin rose again 30 min postexercise. Our data indicates a distinct pattern of exercise-induced insulin modulation in pediatric obesity, possibly modulated by basal insulin concentrations. PMID:24723046

  14. 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

  15. Influence of obesity and insulin sensitivity on insulin signaling genes in human omental and subcutaneous adipose tissue.

    PubMed

    MacLaren, R; Cui, W; Simard, S; Cianflone, K

    2008-02-01

    Obesity and insulin resistance are independent risk factors for metabolic syndrome, diabetes, and cardiovascular disease. Adipose tissue samples from nonobese (NO), insulin-sensitive obese (ISO), and insulin-resistant obese (IRO) subjects from subcutaneous (SC) and omental (OM) adipose tissue (n = 28) were analyzed by microarray and confirmed by real-time PCR. Insulin signaling gene expression changes were greater in OM than in SC tissue and were related to insulin resistance rather than to obesity; few genes correlated with body mass index. Insulin receptor and insulin receptor substrate 1 (IRS-1) increased in the IRO versus pooled insulin-sensitive (NO+ISO) subjects. In glucose transport, PI3Kalpha and PDK2 decreased in IRO subjects, whereas PI3Kgamma, Akt2, GLUT4, and GLUT1 increased. IRS-1 regulators Jnk and IKK increased in IRO (P < 0.01 and P < 0.001 respectively). In protein synthesis, most genes examined were downregulated in IRO subjects, including mTor, Rheb, and 4EBP and eIF members (all P < 0.05). In proliferation, SHC, SOS, and Raf1 (P < 0.05) were increased, whereas Ras and MEK1/2 kinase 1 (P < 0.05) were decreased, in IRO subjects. Finally, in differentiation, PPARgamma, CEBPalpha, and CEBPbeta decreased, whereas PPARdelta, CEBPgamma, and CEBPepsilon increased, in IRO subjects (P < 0.05). Together, microarray and real-time PCR data demonstrate that insulin resistance rather than obesity is associated with altered gene expression of insulin signaling genes, especially in OM adipose tissue. PMID:17986714

  16. A major role of insulin in promoting obesity-associated adipose tissue inflammation

    PubMed Central

    Pedersen, David J.; Guilherme, Adilson; Danai, Laura V.; Heyda, Lauren; Matevossian, Anouch; Cohen, Jessica; Nicoloro, Sarah M.; Straubhaar, Juerg; Noh, Hye Lim; Jung, DaeYoung; Kim, Jason K.; Czech, Michael P.

    2015-01-01

    Objective Adipose tissue (AT) inflammation is associated with systemic insulin resistance and hyperinsulinemia in obese rodents and humans. A longstanding concept is that hyperinsulinemia may promote systemic insulin resistance through downregulation of its receptor on target tissues. Here we tested the novel hypothesis that insulin also impairs systemic insulin sensitivity by specifically enhancing adipose inflammation. Methods Circulating insulin levels were reduced by about 50% in diet-induced and genetically obese mice by treatments with diazoxide or streptozotocin, respectively. We then examined AT crown-like structures, macrophage markers and pro-inflammatory cytokine expression in AT. AT lipogenesis and systemic insulin sensitivity was also monitored. Conversely, insulin was infused into lean mice to determine its affects on the above parameters. Results Lowering circulating insulin levels in obese mice by streptozotocin treatment decreased macrophage content in AT, enhancing insulin stimulated Akt phosphorylation and de novo lipogenesis (DNL). Moreover, responsiveness of blood glucose levels to injected insulin was improved by streptozotocin and diazoxide treatments of obese mice without changes in body weight. Remarkably, even in lean mice, infusion of insulin under constant euglycemic conditions stimulated expression of cytokines in AT. Consistent with these findings, insulin treatment of 3T3-L1 adipocytes caused a 10-fold increase in CCL2 mRNA levels within 6 h, which was blocked by the ERK inhibitor PD98059. Conclusion Taken together, these results indicate that obesity-associated hyperinsulinemia unexpectedly drives AT inflammation in obese mice, which in turn contributes to factors that suppress insulin-stimulated adipocyte DNL and systemic insulin sensitivity. PMID:26137438

  17. 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.

  18. 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. PMID:23822701

  19. Antioxidant supplementation and obesity have independent effects on hepatic oxylipin profiles in insulin-resistant, obesity-prone rats.

    PubMed

    Picklo, Matthew J; Newman, John W

    2015-12-01

    Obesity-induced changes in lipid metabolism are mechanistically associated with the development of insulin resistance and prediabetes. Recent studies have focused on the extent to which obesity-induced insulin resistance is mediated through oxylipins, derived from enzymatic and nonenzymatic lipid peroxidation. Vitamin E and vitamin C are widely used antioxidant supplements, but conflicting data exist as to whether supplementation with vitamins E and C reduces insulin resistance. The purpose of this work is (1) to test the hypothesis that supplementation with vitamin E and vitamin C prevents the development of insulin resistance and (2) to determine the extent to which antioxidant supplementation modifies obesity-induced changes in hepatic oxylipins. Using obesity-prone Sprague-Dawley rats fed a high-fat, hypercaloric diet, we found that vitamin E and C supplementation did not block the development of insulin resistance, despite increased plasma levels of these antioxidants and decreased hepatic F2-isoprostane (F2-IsoP) concentrations. The obese phenotype was associated with increased hepatic concentrations of cytochrome P450 (CYP450)-dependent linoleic acid and α-linolenic acid-derived epoxides. Antioxidant supplementation, but not obesity, decreased levels of the lipoxygenase (LOX)-dependent, arachidonic acid-derived products lipoxin A4 (LXA4), 8,15-dihydroxtetraenoate (8,15-DiHETE), and 5,15-DiHETE. Our data demonstrate that antioxidant supplementation and obesity impact hepatic LOX- and CYP450-dependent oxylipin metabolism.

  20. Systemic inflammation and insulin sensitivity in obese IFN-γ knockout mice

    PubMed Central

    O’Rourke, Robert W.; White, Ashley E.; Metcalf, Monja D.; Winters, Brian R.; Diggs, Brian S.; Zhu, Xinxia; Marks, Daniel L.

    2012-01-01

    Adipose tissue macrophages are important mediators of inflammation and insulin resistance in obesity. IFN-γ is a central regulator of macrophage function. The role of IFN-γ in regulating systemic inflammation and insulin resistance in obesity is unknown. We studied obese IFN-γ knockout mice to identify the role of IFN-γ in regulating inflammation and insulin sensitivity in obesity. IFN-γ-knockout C57Bl/6 mice and wild-type control litter mates were maintained on normal chow or a high fat diet for 13 weeks and then underwent insulin sensitivity testing then sacrifice and tissue collection. Flow cytometry, intracellular cytokine staining, and QRTPCR were used to define tissue lymphocyte phenotype and cytokine expression profiles. Adipocyte size was determined from whole adipose tissue explants examined under immunofluorescence microscopy. Diet-induced obesity induced systemic inflammation and insulin resistance, along with a pan-leukocyte adipose tissue infiltrate that includes macrophages, T-cells, and NK cells. Obese IFN-γ-knockout animals, compared with obese wild-type control animals, demonstrate modest improvements in insulin sensitivity, decreased adipocyte size, and an M2-shift in ATM phenotype and cytokine expression. These data suggest a role for IFN-γ in the regulation of inflammation and glucose homeostasis in obesity though multiple potential mechanisms, including effects on adipogenesis, cytokine expression, and macrophage phenotype. PMID:22386937

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

    PubMed

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

    2016-03-10

    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.

  2. 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

  3. Prevalence of abdominal obesity in Abia State, Nigeria: results of a population-based house-to-house survey

    PubMed Central

    Ijezie, Innocent Chukwuonye; Chuku, Abali; Onyeonoro, Ugochukwu Uchenna; Okpechi, Ikechi Gareth; Madukwe, Okechukwu Ojoemelam; Umeizudike, Theophilus Ifeanyichukwu; Ogah, Okechukwu Samuel

    2013-01-01

    Background and objective Abdominal obesity is associated with the risk of developing disorders, such as diabetes and hypertension. The objective of this study was to investigate the prevalence of abdominal obesity in Abia State, Nigeria. Materials and methods We carried out a cross-sectional study aimed at ascertaining the prevalence of abdominal obesity in Abia State, Nigeria. Participants in the study were recruited from communities in the three senatorial zones in the state. Screening for abdominal obesity was carried out in these subjects using waist circumference (the National Cholesterol Education Program Third Adult Treatment Panel criteria were used). The World Health Organization Stepwise Approach to Surveillance of chronic disease risk factors was used. Body mass index, anthropometric measurements, and other relevant data were also collected. Results Data on waist circumference were obtained from 2,807 subjects. The prevalence of obesity using body mass index in the population was 11.12%. In men and women, it was 7.73%, and 14.37%, respectively. The prevalence of abdominal obesity in the population was 21.75%. In men and women, it was 3.2% and 39.2%, respectively. Conclusion The prevalence of abdominal obesity is high in Nigeria, and needs to be monitored because it is associated with increased cardiovascular risk. PMID:23946664

  4. Taste-induced changes in plasma insulin and glucose turnover in lean and genetically obese rats.

    PubMed

    Ionescu, E; Rohner-Jeanrenaud, F; Proietto, J; Rivest, R W; Jeanrenaud, B

    1988-06-01

    Cephalic-phase insulin release (CPIR) and the changes in glucose turnover induced by saccharin ingestion were studied in freely moving lean and genetically obese fa/fa rats equipped with chronic catheters for blood sampling. Six-hour-fasted lean and obese rats were trained to drink 1 ml sodium saccharin (0.15%) or 1 ml glucose (70%), and blood samples were taken before and after the stimuli. As early as 1-1.5 min poststimulus, there was a significant increase in CPIR in lean and obese rats. The amplitude of the CPIR induced either by saccharin or by glucose in the obese rats was significantly higher than it was in the lean rats. The effect of saccharin ingestion on the hepatic glucose production (HGP) and the rate of glucose disappearance (Rd) was studied in 6-h-fasted lean and obese rats, under non-steady-state conditions, according to a method previously validated. Saccharin ingestion produced a significant increase in HGP and Rd in lean and obese rats compared with basal values. The saccharin-induced increments in HGP and Rd were higher in the obese than in the lean animals. We conclude that saccharin (through taste) appears to elicit parasympathetic (insulin release) and sympathetic (HGP increase) reflexes in lean and obese rats. These taste-induced changes in plasma insulin and glucose turnover are exaggerated in the obese rats and may participate in obesity and in insulin resistance of the overall syndrome.

  5. Effect of folic acid on homocysteine and insulin resistance of overweight and obese children and adolescents

    PubMed Central

    Dehkordi, Elham Hashemi; Sedehi, Morteza; Shahraki, Zohre Gholipour; Najafi, Reza

    2016-01-01

    Background: Considering the increasing trend of childhood obesity and subsequent burden of the disease in Iran and other countries and importance of early life intervention for achieving sustained effect on health of children and adolescents, this study aimed to investigate the effect of two different dose of folic acid on homocysteine (Hcy) level and insulin resistance of obese children. Materials and Methods: In this randomized, double-blind controlled clinical trial study, 60 obese and overweight children aged 5–12 years were enrolled. Selected obese children randomly allocated in two interventional (1 mg/day folic acid and 5 mg/day folic acid, for 8 weeks) and one control groups. Biochemical measurements including folic acid, Hcy, insulin and insulin resistance were measured between and within groups before and after trial. Results: In each group, 20 obese children were studied. The three groups were age and sex matched. After folic acid administration, mean of Hcy, insulin resistance and insulin decreased significantly in two groups which folic acid administrated with two different doses (P < 0.05). The reduction in studied biochemical variables was similar in two interventional groups (1 and 5 mg folic acid daily) (P > 0.05). Mean differences for Hcy, insulin resistance and insulin, in two intervention groups were significantly higher than the control group (P < 0.0001). Mean differences of Hcy, insulin resistance and insulin, in two intervention groups were not different significantly (P > 0.05). Conclusion: The findings of current trial showed that folic acid in two studied doses could be a safe and effective supplement for obese children to reduce Hcy level and insulin resistance, which consequently could prevent obesity-related complications including cardiovascular and metabolic disorders. PMID:27274503

  6. 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.

  7. 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

  8. REDUCED GLUTEAL EXPRESSION OF ADIPOGENIC AND LIPOGENIC GENES IN BLACK SOUTH AFRICAN WOMEN IS ASSOCIATED WITH OBESITY-RELATED INSULIN RESISTANCE

    PubMed Central

    Goedecke, Julia H.; Evans, Juliet; Keswell, Dheshnie; Stimson, Roland H.; Livingstone, Dawn E.W.; Hayes, Philip; Adams, Kevin; Dave, Joel A.; Victor, Hendriena; Levitt, Naomi S.; Lambert, Estelle V.; Walker, Brian R.; Seckl, Jonathan R.; Olsson, Tommy; Kahn, Steven E.

    2014-01-01

    Context Black South African women are less insulin sensitive than their white counterparts, despite less central and greater peripheral fat deposition. We hypothesized that this paradox may be explained, in part, by differences in the adipogenic capacity of subcutaneous adipose tissue (SAT). Objective To measure adipogenic and lipogenic gene expression in abdominal and gluteal SAT depots, and determine their relationships with insulin sensitivity (SI) in South African women. Design Cross-sectional. Participants 14 normal-weight (BMI <25 kg/m2) black, 13 normal-weight white, 14 obese (BMI >30 kg/m2) black and 13 obese white premenopausal South African women. Main outcomes SI (frequently sampled intravenous glucose tolerance test) in relation to expression of adipogenic and lipogenic genes in abdominal and gluteal SAT depots. Results With increasing BMI, black women had less visceral fat (P=0.03) and more abdominal (P=0.017) and gynoid (P=0.041) SAT but had lower SI (P<0.01) than white women. The expression of adipogenic and lipogenic genes was proportionately lower with obesity in black, but not white women in the gluteal and deep SAT depots (P<0.05 for ethnicity x BMI effect). In black women only, the expression of these genes correlated positively with SI (all P<0.05), independently of age and fat mass. Conclusions Obese black women have reduced SAT expression of adipogenic and lipogenic genes compared to white women, which associates with reduced SI. These findings suggest that obesity in black women impairs SAT adipogenesis and storage, potentially leading to insulin resistance and increased risk of type 2 diabetes. PMID:21956425

  9. Systematic review on the association of abdominal obesity in children and adolescents with cardio-metabolic risk factors

    PubMed Central

    Kelishadi, Roya; Mirmoghtadaee, Parisa; Najafi, Hananeh; Keikha, Mojtaba

    2015-01-01

    Background: The adverse health effects of abdominal obesity are well documented in adults, but such association remains to be determined in the pediatric age group. This study aims to perform a systematic review on the association between abdominal obesity and cardio-metabolic factors such as dyslipidemia, hypertension, and hyperglycemia among children and adolescents. Materials and Methods: A systematic literature search was conducted using PubMed, Scopus and Google Scholar databases to May 2014. Two independent reviewers identified relevant papers in several steps. After studying the titles and texts of documents, repeated and irrelevant ones were excluded. The search was refined to the English language. We did not consider any time limitation. Studies with different measuring methods of abdominal obesity were included. Studies with abdominal obese patients secondary to other disease were excluded from the study. In final, the data of association of cardio-metabolic risk factors and abdominal obesity extracted from studies. Results: Overall, 3966 articles were reviewed, and 61 of them were studied according to the inclusion and exclusion criteria. Waist circumference (WC), waist-to-height ratio, and waist-to-hip ratio were the most common indexes used for defining abdominal obesity. The association of high blood pressure with increasing WC was seen in several studies. The association of other cardio-metabolic risk factors was seen in some studies. Conclusion: Whatever the definition used for abdominal obesity and whatever the methods used for anthropometric measurements, central body fat deposition in children and adolescents increases the risk of cardio-metabolic risk factors. Therefore, more attention should be paid to abdominal obesity of children and adolescents both in clinical practice and in epidemiological studies. PMID:26109978

  10. 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.

  11. 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.

  12. Differential insulin response to myo-inositol administration in obese polycystic ovary syndrome patients.

    PubMed

    Genazzani, Alessandro D; Prati, Alessia; Santagni, Susanna; Ricchieri, Federica; Chierchia, Elisa; Rattighieri, Erica; Campedelli, Annalisa; Simoncini, Tommaso; Artini, Paolo G

    2012-12-01

    Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, chronic anovulation, polycystic ovaries at ultrasound evaluation, and quite frequently by insulin resistance or compensatory hyperinsulinemia. Attention has been given to the role of inositol-phosphoglycan (IPG) mediators of insulin action and growing evidences suggest that a deficiency of D-chiro-inositol (DCI) containing IPG might be at the basis of insulin resistance, frequent in PCOS patients. On such basis, we investigated the efficacy on insulin sensitivity and hormonal parameters of 8 weeks treatment with myo-inositol (MYO) (Inofert, ItalPharmaco, Milano, Italy) at the dosage of 2 g day in a group (n = 42) of obese PCOS patients,. After the treatment interval body mass index (BMI) and insulin resistance decreased together with luteinizing hormone (LH), LH/FSH and insulin. When subdividing the patients according to their fasting insulin levels, Group A (n = 15) insulin below 12 µU/ml and Group B (n = 27) insulin above 12 µU/ml, MYO treatment induced similar changes in both groups but only patients of Group B showed the significant decrease of both fasting insulin plasma levels (from 20.3 ± 1.8 to 12.9 ± 1.8 µU/ml, p < 0.00001) and of area under the curve (AUC) of insulin under oral glucose tolerance test (OGTT). In conclusion, our study supports the hypothesis that MYO administration is more effective in obese patients with high fasting insulin plasma levels.

  13. 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

  14. Abdominal obesity is associated with microalbuminuria and an elevated cardiovascular risk profile in patients with hypertension

    PubMed Central

    Thoenes, Martin; Reil, Jan-Christian; Khan, Bobby Varkey; Bramlage, Peter; Volpe, Massimo; Kirch, Wilhelm; Böhm, Michael

    2009-01-01

    Background Overweight and obesity are frequently associated with preventable death and have emerged as a major challenge to public health. There is an ongoing debate on the role of abdominal obesity and its value in predicting cardiovascular and renal outcomes. The present analysis evaluates the prevalence of microalbuminuria (MAU) and conventional cardiovascular risk factors in relation to measures of general and abdominal obesity. Methods In this multinational, observational study, 20828 hypertensive out-patients from 26 countries including Europe, North and Latin America, Middle East, and Asia were analyzed. Urinary dipstick screening for MAU was performed as well as data on patient demographics, anthropometric measures, cardiovascular risk factors, comorbid conditions, and cardiovascular drug therapy collected. MAU prevalence was determined by a stepwise logistic regression analysis with cardiovascular risk factors as univariate. Results In the univariate analysis, MAU prevalence systematically increased with body mass index (BMI) from 54.4% (1st tertial) to 62.1% (3rd tertial) (p < 0.0001), an increase which was also observed for waist circumference (WC). At any level of BMI, MAU increased with WC from 53.5%, 54.8%, and 55.0% (1st tertial of WC in all three BMI tertials) to 61.4%, 62.1%, and 64.0% (3rd tertial of WC in all BMI tertials) (p < 0.0001). In the multivariate analysis, WC, but not BMI was independently associated with MAU. Furthermore, overweight/obesity were associated with the presence of modifiable and nonmodifiable risk factors. Conclusion An abnormal WC, but not BMI appears to be independently associated with MAU, an early marker of cardiovascular and renal risk. Increasing WC confers an incremental risk for MAU at any level of BMI, underlining the prognostic importance of abdominal fat accumulation beyond general obesity. PMID:19649308

  15. Myeloperoxidase deletion prevents high-fat diet-induced obesity and insulin resistance.

    PubMed

    Wang, Qilong; Xie, Zhonglin; Zhang, Wencheng; Zhou, Jun; Wu, Yue; Zhang, Miao; Zhu, Huaiping; Zou, Ming-Hui

    2014-12-01

    Activation of myeloperoxidase (MPO), a heme protein primarily expressed in granules of neutrophils, is associated with the development of obesity. However, whether MPO mediates high-fat diet (HFD)-induced obesity and obesity-associated insulin resistance remains to be determined. Here, we found that consumption of an HFD resulted in neutrophil infiltration and enhanced MPO expression and activity in epididymal white adipose tissue, with an increase in body weight gain and impaired insulin signaling. MPO knockout (MPO(-/-)) mice were protected from HFD-enhanced body weight gain and insulin resistance. The MPO inhibitor 4-aminobenzoic acid hydrazide reduced peroxidase activity of neutrophils and prevented HFD-enhanced insulin resistance. MPO deficiency caused high body temperature via upregulation of uncoupling protein-1 and mitochondrial oxygen consumption in brown adipose tissue. Lack of MPO also attenuated HFD-induced macrophage infiltration and expression of proinflammatory cytokines. We conclude that activation of MPO in adipose tissue contributes to the development of obesity and obesity-associated insulin resistance. Inhibition of MPO may be a potential strategy for prevention and treatment of obesity and insulin resistance.

  16. Relationship between bone mineral density, leptin and insulin concentration in Brazilian obese adolescents.

    PubMed

    do Prado, Wagner Luiz; de Piano, Aline; Lazaretti-Castro, Marise; de Mello, Marco Túlio; Stella, Sérgio Garcia; Tufik, Sergio; do Nascimento, Cláudia Maria Oller; Oyama, Lila Missae; Lofrano, Mara Cristina; Tock, Lian; Caranti, Danielle Arisa; Dâmaso, Ana Raimunda

    2009-01-01

    Despite the epidemic of adolescent obesity, the effect of obesity and hormones on bone mineral accrual during growth is poorly understood. Studies using dual-energy X-ray to examine the effect of obesity on bone mass in children and adolescents have yielded conflicting results. The aim of this study was to explore the combined and independent contributions of body mass index, body composition, leptin, insulin, glucose levels and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) to bone mineral density (BMD) and bone mineral content in a group of Brazilian obese adolescents. This study included 109 post-pubescent obese adolescents. A whole-body dual-energy X-ray absorptiometry scan was performed,using a HOLOGIC QDR4200, to determine whole-body BMD and body composition. Blood samples were collected in the outpatient clinic after an overnight fast, and evaluated for fasting blood glucose and immunoreactive insulin. Leptin levels were assessed with a radioimmunoassay kit. Insulin resistance was assessed by HOMA-IR and the quantitative insulin sensitivity check index. Our results showed that insulin levels and HOMA-IR correlated negatively with BMD and a linear regression analysis showed that serum leptin is inversely associated to BMD adjusted for body mass. In conclusion, our data support the hypothesis that leptin, insulin and HOMA-IR are inversely associated with BMD and play a significant direct role in bone metabolism. PMID:19466592

  17. 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

  18. 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 ...

  19. Insulin Suppresses TNF-dependent Early Osteoarthritic Changes Associated with Obesity and Type 2 Diabetes

    PubMed Central

    Hamada, Daisuke; Maynard, Robert; Schott, Eric; Drinkwater, Christopher J.; Ketz, John P.; Kates, Stephen L.; Jonason, Jennifer H.; Hilton, Matthew J.; Zuscik, Michael J.; Mooney, Robert A.

    2015-01-01

    Objective Obesity is a chronic inflammatory state that is associated with insulin resistance and type 2 diabetes (T2D), as well as an increased risk for osteoarthritis (OA). To define the links between inflammation of obesity, insulin resistance, and OA, two hypotheses were tested: 1) TNF is critical in mediating these OA changes and 2) insulin has direct effects on the synovial joint that are compromised by insulin resistance. Methods Effects of TNF and insulin on catabolic gene expression were determined in fibroblast-like synoviocytes (FLSs) isolated from human osteoarthritic synovium. Synovial TNF expression and OA progression were examined in high fat-fed (HF) obese/T2D mice and TNF knockout mice. Insulin resistance was investigated in synovium from T2D patients. Results Insulin receptors (IR) were abundant in mouse and human synovial membrane. FLSs were insulin responsive with dose dependent phosphorylation of IR and Akt. While TNF markedly increased expression and release of MMP1, MMP13, and ADAMTS4 by FLSs, insulin selectively inhibited the effects by >50%. TNF expression and abundance were elevated in synovium from obese, T2D mice. In TNF knockout mice, increases in osteophyte formation and synovial hyperplasia associated with HF diet were blunted. Synovium from diabetic patients contained markedly more macrophages, TNF levels were elevated, and insulin-dependent phosphorylation of IR and Akt was blunted compared to non-diabetics. Conclusion TNF appears involved in mediating the advanced progression of OA seen in T2D. While insulin plays a protective, anti-inflammatory role in the synovium, insulin resistance of diabetes may impair this protective effect and promote OA. PMID:26713606

  20. 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 +/-...

  1. Insulin action in morbid obesity: a focus on muscle and adipose tissue.

    PubMed

    Mitrou, Panayota; Raptis, Sotirios A; Dimitriadis, George

    2013-01-01

    The aim of this review is to summarize the mechanisms underlying insulin resistance in morbid obesity. Glucose regulation by insulin depends on the suppression of endogenous glucose production and stimulation of glucose disposal. In morbid obesity, glucose production by the liver is increased. Moreover, the sensitivity of glucose metabolism to insulin is impaired both in muscle (due to defects in insulin-stimulated glucose utilization and decreased blood flow) and in adipose tissue (due to decreased blood flow). However, recent studies suggest that expanded total fat mass becomes a major consumer of glucose providing a sink for glucose and compensating for insulin resistance. Metabolism and immunity are closely linked. Bearing in mind the crosstalk between inflammatory pathways and the insulin signaling cascade, adipose tissue derived cytokines may represent a link between inflammation and metabolic signals and mediate, at least in part, insulin resistance. Adipose tissue plays a crucial role by buffering daily influx of dietary fat, suppressing the release of non-esterified fatty acids into the circulation and increasing triacylglycerol clearance. However, in morbid obesity there is an impairment of the normal ability of adipose tissue to buffer fatty acids, despite hyperinsulinemia. Lipotoxicity gradually impairs insulin action in the liver and muscle, aggravating insulin resistance.

  2. 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.

  3. Possible role of cytosolic free calcium concentrations in mediating insulin resistance of obesity and hyperinsulinemia.

    PubMed Central

    Draznin, B; Sussman, K E; Eckel, R H; Kao, M; Yost, T; Sherman, N A

    1988-01-01

    Insulin- and glyburide-stimulated changes in cytosolic free calcium concentrations [( Ca2+]i) were studied in gluteal adipocytes obtained from six obese women (139 +/- 3% ideal body wt) and six healthy, normal weight age- and sex-matched controls. Biopsies were performed after an overnight fast and twice (at 3 and 6 h) during an insulin infusion (40 mU/m2 per min) (euglycemic clamp). In adipocytes obtained from normal subjects before insulin infusion, insulin (10 ng/ml) increased [Ca2+]i from 146 +/- 26 nM to 391 +/- 66 nM. Similar increases were evoked by 2 microM glyburide (329 +/- 41 nM). After 3 h of insulin infusion, basal [Ca2+]i rose to 234 +/- 21 nM, but the responses to insulin and glyburide were completely abolished. In vitro insulin-stimulated 2-deoxyglucose uptake was reduced by insulin and glucose infusion (25% stimulation before infusion, 5.4% at 3 h, and 0.85% at 6 h of infusion). In obese patients, basal adipocyte [Ca2+]i was increased (203 +/- 14 nM, P less than 0.05 vs. normals). The [Ca2+]i response demonstrated resistance to insulin (230 +/- 23 nM) and glyburide (249 +/- 19 nM) stimulation. Continuous insulin infusion increased basal [Ca2+]i (244 +/- 24 nM) and there was no response to either insulin or glyburide at 3 and 6 h of study. Rat adipocytes were preincubated with 1-10 mM glucose and 10 ng/ml insulin for 24 h. Measurements of 2-deoxyglucose uptake demonstrated insulin resistance in these cells. Under these experimental conditions, increased levels of [Ca2+]i that were no longer responsive to insulin were demonstrated. Verapamil in the preincubation medium prevented the development of insulin resistance. PMID:3143744

  4. 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.

  5. Pancreatic β-Cell Adaptive Plasticity in Obesity Increases Insulin Production but Adversely Affects Secretory Function.

    PubMed

    Alarcon, Cristina; Boland, Brandon B; Uchizono, Yuji; Moore, Patrick C; Peterson, Bryan; Rajan, Suryalekha; Rhodes, Olivia S; Noske, Andrew B; Haataja, Leena; Arvan, Peter; Marsh, Bradly J; Austin, Jotham; Rhodes, Christopher J

    2016-02-01

    Pancreatic β-cells normally produce adequate insulin to control glucose homeostasis, but in obesity-related diabetes, there is a presumed deficit in insulin production and secretory capacity. In this study, insulin production was assessed directly in obese diabetic mouse models, and proinsulin biosynthesis was found to be contrastingly increased, coupled with a significant expansion of the rough endoplasmic reticulum (without endoplasmic reticulum stress) and Golgi apparatus, increased vesicular trafficking, and a depletion of mature β-granules. As such, β-cells have a remarkable capacity to produce substantial quantities of insulin in obesity, which are then made available for immediate secretion to meet increased metabolic demand, but this comes at the price of insulin secretory dysfunction. Notwithstanding, it can be restored. Upon exposing isolated pancreatic islets of obese mice to normal glucose concentrations, β-cells revert back to their typical morphology with restoration of regulated insulin secretion. These data demonstrate an unrealized dynamic adaptive plasticity of pancreatic β-cells and underscore the rationale for transient β-cell rest as a treatment strategy for obesity-linked diabetes. PMID:26307586

  6. Mesenteric Fat Lipolysis Mediates Obesity-Associated Hepatic Steatosis and Insulin Resistance.

    PubMed

    Wueest, Stephan; Item, Flurin; Lucchini, Fabrizio C; Challa, Tenagne D; Müller, Werner; Blüher, Matthias; Konrad, Daniel

    2016-01-01

    Hepatic steatosis and insulin resistance are among the most prevalent metabolic disorders and are tightly associated with obesity and type 2 diabetes. However, the underlying mechanisms linking obesity to hepatic lipid accumulation and insulin resistance are incompletely understood. Glycoprotein 130 (gp130) is the common signal transducer of all interleukin 6 (IL-6) cytokines. We provide evidence that gp130-mediated adipose tissue lipolysis promotes hepatic steatosis and insulin resistance. In obese mice, adipocyte-specific gp130 deletion reduced basal lipolysis and enhanced insulin's ability to suppress lipolysis from mesenteric but not epididymal adipocytes. Consistently, free fatty acid levels were reduced in portal but not in systemic circulation of obese knockout mice. Of note, adipocyte-specific gp130 knockout mice were protected from high-fat diet-induced hepatic steatosis as well as from insulin resistance. In humans, omental but not subcutaneous IL-6 mRNA expression correlated positively with liver lipid accumulation (r = 0.31, P < 0.05) and negatively with hyperinsulinemic-euglycemic clamp glucose infusion rate (r = -0.28, P < 0.05). The results show that IL-6 cytokine-induced lipolysis may be restricted to mesenteric white adipose tissue and that it contributes to hepatic insulin resistance and steatosis. Therefore, blocking IL-6 cytokine signaling in (mesenteric) adipocytes may be a novel approach to blunting detrimental fat-liver crosstalk in obesity.

  7. Hypertension and insulin resistance are not directly related in obese dogs.

    PubMed

    Rocchini, Albert P; Yang, John Q; Gokee, Amy

    2004-05-01

    In dogs fed a high-fat diet, we determined whether there was a direct relation between obesity-induced insulin resistance and obesity-induced hypertension. Thirty-six adult mongrel dogs were chronically instrumented and assigned to receive either a high-fat diet alone (n=7) or a high-fat diet combined with a low-sodium diet plus furosemide (n=6), prazosin plus atenolol (n=7), clonidine (n=10), or aspirin (n=6). Blood pressure, heart rate, and body weight were measured daily. Insulin resistance was assessed with a single-dose euglycemic hyperinsulinemic clamp (2 mU x kg(-1) x min(-1)) before and after 1, 3, and 6 weeks of the high-fat diet. The low-salt diet plus furosemide, prazosin plus atenolol, and clonidine treatments prevented the hypertension associated with feeding the dogs a high-fat diet. Only clonidine treatment totally prevented the development of insulin resistance, and high-dose aspirin, known to prevent insulin resistance by inhibition of the activity of IkappaB kinase-beta, decreased the degree of insulin resistance by almost 70%. However, aspirin had no effect on the development of hypertension. We conclude that obesity-induced hypertension and obesity-induced insulin resistance are not directly related. In addition, there is a suggestion that insulin resistance in this experimental model is mediated through the central and or peripheral alpha2-adrenoceptors, whereas hypertension is mediated through the alpha1- and or beta-adrenoceptors.

  8. Phenotypic characteristics associated with insulin resistance in metabolically obese but normal-weight young women.

    PubMed

    Dvorak, R V; DeNino, W F; Ades, P A; Poehlman, E T

    1999-11-01

    Metabolically obese, normal-weight (MONW) individuals are a hypothesized subgroup of the general population. These normal-weight individuals potentially display a cluster of obesity-related features, although this has not been systematically tested in young women. We hypothesized that MONW young women would display higher levels of total and visceral fat and lower levels of physical activity than normal women. In a cohort of 71 healthy nonobese women (21-35 years old), we identified MONW women based on cut points for insulin sensitivity (normal = glucose disposal >8 mg x min(-1) x kg(-1) of fat-free mass [FFM], n = 58; impaired = glucose disposal <8 ml x min(-1) x kg(-1) of FFM, n = 13). Thereafter, we measured body composition (dual energy X-ray absorptiometry) and body fat distribution (computed tomography), cardiorespiratory fitness (VO2max on a treadmill), physical activity energy expenditure (doubly labeled water and indirect calorimetry), glucose tolerance (oral glucose tolerance test), serum lipid profile, and dietary intake. We found a higher body fat percentage (32 +/- 6 vs. 27 +/- 6%, P = 0.01) and higher subcutaneous (213 +/- 61 vs. 160 +/- 78 cm2, P = 0.03) and visceral (44 +/- 16 vs. 35 +/- 14 cm2, P < 0.05) abdominal adiposity in the MONW group versus the normal group. The MONW group showed a lower physical activity energy expenditure (2.66 +/- 0.92 vs. 4.39 +/- 1.50 MJ/day, P = 0.01), but no difference in cardiorespiratory fitness was noted between groups. In conclusion, despite a normal body weight, a subset of young, apparently healthy women displayed a cluster of risky phenotypic characteristics that, if left untreated, may eventually predispose them to type 2 diabetes and cardiovascular disease.

  9. SORCS1 polymorphism and insulin secretion in obese women with polycystic ovary syndrome.

    PubMed

    Hrovat, Ana; Kravos, Nika Aleksandra; Goričar, Katja; Jensterle Sever, Mojca; Janež, Andrej; Dolžan, Vita

    2016-01-01

    We investigated the influence of SORCS1 polymorphisms on insulin secretion in obese women with PCOS. Metabolic status was recorded in 50 clinically well characterized PCOS patients. Oral glucose tolerance test was performed and laboratory parameters of insulin resistance measured. All patients were genotyped for SORCS1 rs1358030, rs1416406 and rs11192966 polymorphisms. Statistical analysis was performed using the Mann-Whitney test. SORCS1 rs1416406 significantly influenced stimulated glucose plasma levels (p = 0.006) and increased glucose stimulated insulin secretion (p = 0.034). None of the polymorphisms influenced insulin resistance as measured by homeostatic model assessment. We report for the first time the relevance of SORCS1 polymorphisms for glycemic control and glucose stimulated insulin secretion in obese women with PCOS. PMID:27052493

  10. 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.

  11. Angiotensinogen gene polymorphism (Met235Thr) influences visceral obesity and insulin resistance in obese Japanese women.

    PubMed

    Takakura, Yasuto; Yoshida, Toshihide; Yoshioka, Keiji; Umekawa, Tsunekazu; Kogure, Akinori; Toda, Hitoshi; Kagawa, Keizo; Fukui, Susumu; Yoshikawa, Toshikazu

    2006-06-01

    To investigate the relationship between angiotensinogen (AGT) Met235Thr polymorphism (M235T) and human obesity, because AGT is regarded as one of the cytokines produced from adipocytes and serum AGT concentrations are reported to be positively correlated with body mass index. One hundred and twenty obese Japanese women (age, 58.8+/-9.4 years; body mass index, 32.2+/-4.9 kg/m(2)) were enrolled. Angiotensinogen genotypes were determined with a fluorescent allele-specific DNA primer assay system. Subjects were divided into M/M, M/T, and T/T groups. Control subjects comprised 146 healthy age-matched women. Clinical characteristics and the effects of diet and exercise therapy for 6 months were compared among the 3 genotypes. The genotype frequencies of AGT M235T polymorphism were in accordance with the Hardy-Weinberg equation (obese: M/M, 6.7%; M/T, 27.5%; T/T, 65.8%; control: M/M, 6.8%; M/T, 21.2%; T/T, 71.9%). The frequency of the T allele did not differ between obese and control subjects (0.80 vs 0.83). As the number of obese women with M/M genotype was only 8, comparisons of the characteristics and outcomes of weight reduction therapy were performed only between subjects with M/T genotype and T/T genotype. In the T/T group, % body fat and waist circumference at baseline were significantly greater than in the M/T group (36.3%+/-4.8% vs 33.8%+/-4.7%, P=.0105; 107.9+/-10.9 vs 102.6+/-7.9 cm, P=.0428, respectively). Before the weight reduction therapy, significantly higher insulin and higher homeostasis model assessment (HOMA-R) were demonstrated in the T/T group than in the M/T group (9.1+/-5.5 microU/mL vs 5.9+/-4.4 microU/mL, P=.0056; 2.3+/-1.4 vs 1.6+/-1.3, P=.0252, respectively). Both systolic and diastolic blood pressure at baseline in the T/T group tended to be higher than those in the M/T group, but the differences were not significant. No genotype-dependent difference in energy expenditure or outcome of weight reduction therapy was observed with respect to AGT

  12. Smoking Is Associated with More Abdominal Fat in Morbidly Obese Patients

    PubMed Central

    Casagrande, Daniela; Wagner, Mario; Mottin, Cláudio

    2015-01-01

    Introduction While the association between cigarette smoking and abdominal fat has been well studied in normal and overweight patients, data regarding the influence of tobacco use in patients with morbid obesity remain scarce. The aim of this study is to evaluate body fat distribution in morbidly obese smokers. Methods We employed a cross-sectional study and grouped severely obese patients (body mass index [BMI] >40 kg/m2 or >35 kg/m2 with comorbidities) according to their smoking habits (smokers or non-smokers). We next compared the anthropometrical measurements and body composition data (measured by electric bioimpedance) of both groups. We analyzed the effect of smoking on body composition variables using univariate and multiple linear regression (MLR); differences are presented as regression coefficients (b) and their respective 95% confidence intervals. Results We included 536 morbidly obese individuals, 453 (84.5%) non-smokers and 83 (15.5%) smokers. Male smokers had a higher BMI (b=3.28 kg/m2, p=0.036), larger waist circumference (b=6.07 cm, p=0.041) and higher percentage of body fat (b=2.33%, p=0.050) than non-smokers. These differences remained significant even after controlling for confounding factors. For females, the only significant finding in MLR was a greater muscle mass among smokers (b=1.34kg, p=0.028). No associations were found between tobacco load measured in pack-years and anthropometric measures or body composition. Discussion Positive associations between smoking and BMI, and waist circumference and percentage of body fat, were found among male morbidly obese patients, but not among females. To the best of our knowledge, this study is the first investigation of these aspects in morbidly obese subjects. We speculate that our findings may indicate that the coexistence of morbid obesity and smoking helps to explain the more serious medical conditions, particularly cardiovascular diseases and neoplasms, seen in these patients. PMID:25978682

  13. Arsenic methylation capacity and obesity are associated with insulin resistance in obese children and adolescents.

    PubMed

    Lin, Hsiu-Chen; Huang, Yung-Kai; Shiue, Horng-Sheng; Chen, Liang-Sien; Choy, Cheuk-Sing; Huang, Shiau-Rung; Han, Bor-Cheng; Hsueh, Yu-Mei

    2014-12-01

    The goal of the present study was to compare the arsenic methylation capacities in elementary school and junior high school students in an area of Taiwan with low arsenic exposure, and explore the influence of both arsenic methylation capacity and obesity on insulin resistance in these children and adolescents using the HOMA-IR index. We recruited 303 elementary school students and 319 junior high school students in Taipei City from September 2007 to November 2011. Concentrations of inorganic arsenic (arsenite + arsenate), monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)) were determined by a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Insulin resistance was determined by HOMA-IR. Elementary school students had significantly lower inorganic arsenic percentage and a higher DMA(V) percentage than junior high school students. It seems that the former had better arsenic methylation capability than the latter. The HOMA-IR value was significantly and positively related to the sum of the urinary inorganic and methylated arsenic (TotalAs) concentrations and also the BMI Z score, with the regression coefficients (β) being 0.058 (p < 0.001) and 0.001 (p = 0.027), respectively. The higher BMI values and higher TotalAs concentration were associated with higher HOMA-IR values in children and adolescents in Taiwan. PMID:25241017

  14. Arsenic methylation capacity and obesity are associated with insulin resistance in obese children and adolescents.

    PubMed

    Lin, Hsiu-Chen; Huang, Yung-Kai; Shiue, Horng-Sheng; Chen, Liang-Sien; Choy, Cheuk-Sing; Huang, Shiau-Rung; Han, Bor-Cheng; Hsueh, Yu-Mei

    2014-12-01

    The goal of the present study was to compare the arsenic methylation capacities in elementary school and junior high school students in an area of Taiwan with low arsenic exposure, and explore the influence of both arsenic methylation capacity and obesity on insulin resistance in these children and adolescents using the HOMA-IR index. We recruited 303 elementary school students and 319 junior high school students in Taipei City from September 2007 to November 2011. Concentrations of inorganic arsenic (arsenite + arsenate), monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)) were determined by a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Insulin resistance was determined by HOMA-IR. Elementary school students had significantly lower inorganic arsenic percentage and a higher DMA(V) percentage than junior high school students. It seems that the former had better arsenic methylation capability than the latter. The HOMA-IR value was significantly and positively related to the sum of the urinary inorganic and methylated arsenic (TotalAs) concentrations and also the BMI Z score, with the regression coefficients (β) being 0.058 (p < 0.001) and 0.001 (p = 0.027), respectively. The higher BMI values and higher TotalAs concentration were associated with higher HOMA-IR values in children and adolescents in Taiwan.

  15. 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

  16. The early origins of obesity and insulin resistance: timing, programming and mechanisms.

    PubMed

    Nicholas, L M; Morrison, J L; Rattanatray, L; Zhang, S; Ozanne, S E; McMillen, I C

    2016-02-01

    Maternal obesity is associated with an increased risk of developing gestational diabetes mellitus and it also results in an increased risk of giving birth to a large baby with increased fat mass. Furthermore, it is also contributes to an increased risk of obesity and insulin resistance in the offspring in childhood, adolescence and adult life. It has been proposed that exposure to maternal obesity may therefore result in an 'intergenerational cycle' of obesity and insulin resistance. There is significant interest in whether exposure to maternal obesity around the time of conception alone contributes directly to poor metabolic outcomes in the offspring and whether dieting in the obese mother before pregnancy or around the time of conception has metabolic benefits for the offspring. This review focusses on experimental and clinical studies that have investigated the specific impact of exposure to maternal obesity during the periconceptional period alone or extending beyond conception on adipogenesis, lipogenesis and on insulin signalling pathways in the fat, liver and muscle of the offspring. Findings from these studies highlight the need for a better evidence base for the development of dietary interventions in obese women before pregnancy and around the time of conception to maximize the metabolic benefits and minimize the metabolic costs for the next generation.

  17. The Third National Health and Morbidity Survey: prevalence of obesity, and abdominal obesity among the Malaysian elderly population.

    PubMed

    Suzana, S; Kee, C C; Jamaludin, A R; Noor Safiza, M N; Khor, G L; Jamaiyah, H; Geeta, A; Ahmad Ali, Z; Rahmah, R; Ruzita, A T; Ahmad Fauzi, Y

    2012-03-01

    Obesity is an emerging public health threat in the elderly population in developing countries. Hence, the Third National Health and Morbidity Survey has assessed 4746 individuals aged 60 years and older recruited through a household survey to determine the prevalence of adiposity using body mass index and waist circumference. The national's prevalence of overweight and obesity in men was 29.2% (95% confidence interval [CI] = 27.2-31.3) and 7.4% (95% CI = 6.4-8.6), respectively. However, the prevalence decreased with age. The figures in women were 30.3% (95% CI = 28.5-32.1) and 13.8% (95% CI = 12.5-15.2), respectively. The prevalence of abdominal obesity was 21.4% (95%CI = 20.2-22.6), with 7.7% (95% CI = 6.7-9.0) in men and 33.4% (95% CI = 31.4-35.3) in women. Predictors of adiposity include the following: Malay and Indian ethnicity, higher education level, higher household income, from urban area, and being married. In conclusion, adiposity affects about one third of the Malaysian elderly population, especially those of the younger age group, women, and those with higher socioeconomic status.

  18. 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

  19. Novel adipocyte aminopeptidases are selectively upregulated by insulin in healthy and obese rats.

    PubMed

    Alponti, Rafaela Fadoni; Alves, Patricia Lucio; Silveira, Paulo Flavio

    2016-02-01

    The lack of a complete assembly of the sensitivity of subcellular aminopeptidase (AP) activities to insulin in different pathophysiological conditions has hampered the complete view of the adipocyte metabolic pathways and its implications in these conditions. Here we investigated the influence of insulin on basic AP (APB), neutral puromycin-sensitive AP (PSA), and neutral puromycin-insensitive AP (APM) in high and low density microsomal and plasma membrane fractions from adipocytes of healthy and obese rats. Catalytic activities of these enzymes were fluorometrically monitoring in these fractions with or without insulin stimulus. Canonical traffic such as insulin-regulated AP was not detected for these novel adipocyte APs in healthy and obese rats. However, insulin increased APM in low density microsomal and plasma membrane fractions from healthy rats, APB in high density microsomal fraction from obese rats and PSA in plasma membrane fraction from healthy rats. A new concept of intracellular compartment-dependent upregulation of AP enzyme activities by insulin emerges from these data. This relatively selective regulation has pathophysiological significance, since these enzymes are well known to act as catalysts and receptor of peptides directly related to energy metabolism. Overall, the regulation of each one of these enzyme activities reflects certain dysfunction in obese individuals.

  20. 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.

  1. Adipose tissue monomethyl branched chain fatty acids and insulin sensitivity: effects of obesity and weight loss

    PubMed Central

    Su, Xiong; Magkos, Faidon; Zhou, Dequan; Eagon, J. Christopher; Fabbrini, Elisa; Okunade, Adewole L.; Klein, Samuel

    2014-01-01

    Objective An increase in circulating branched-chain amino acids (BCAA) is associated with insulin resistance. Adipose tissue is a potentially important site for BCAA metabolism. We evaluated whether monomethyl branched chain fatty acids (mmBCFA) in adipose tissue, which are likely derived from BCAA catabolism, are associated with insulin sensitivity. Design and Methods Insulin-stimulated glucose disposal was determined by using the hyperinsulinemic-euglycemic clamp procedure with stable isotope glucose tracer infusion, in 9 lean and 9 obese subjects, and in a separate group of 9 obese subjects before and 1 year after Roux-en-Y gastric bypass (RYGB) surgery (38% weight loss). Adipose tissue mmBCFA content was measured in tissue biopsies taken in the basal state. Results Total adipose tissue mmBCFA content was ~30% lower in obese than lean subjects (P = 0.02), and increased by ~65% after weight loss in the RYGB group (P = 0.01). Adipose tissue mmBCFA content correlated positively with skeletal muscle insulin sensitivity (R2 = 35%, P = 0.01, n = 18). Conclusions These results demonstrate a novel association between adipose tissue mmBCFA content and obesity-related insulin resistance. Additional studies are needed to determine whether the association between adipose tissue mmBCFA and muscle insulin sensitivity is causal or a simple association. PMID:25328153

  2. Novel adipocyte aminopeptidases are selectively upregulated by insulin in healthy and obese rats.

    PubMed

    Alponti, Rafaela Fadoni; Alves, Patricia Lucio; Silveira, Paulo Flavio

    2016-02-01

    The lack of a complete assembly of the sensitivity of subcellular aminopeptidase (AP) activities to insulin in different pathophysiological conditions has hampered the complete view of the adipocyte metabolic pathways and its implications in these conditions. Here we investigated the influence of insulin on basic AP (APB), neutral puromycin-sensitive AP (PSA), and neutral puromycin-insensitive AP (APM) in high and low density microsomal and plasma membrane fractions from adipocytes of healthy and obese rats. Catalytic activities of these enzymes were fluorometrically monitoring in these fractions with or without insulin stimulus. Canonical traffic such as insulin-regulated AP was not detected for these novel adipocyte APs in healthy and obese rats. However, insulin increased APM in low density microsomal and plasma membrane fractions from healthy rats, APB in high density microsomal fraction from obese rats and PSA in plasma membrane fraction from healthy rats. A new concept of intracellular compartment-dependent upregulation of AP enzyme activities by insulin emerges from these data. This relatively selective regulation has pathophysiological significance, since these enzymes are well known to act as catalysts and receptor of peptides directly related to energy metabolism. Overall, the regulation of each one of these enzyme activities reflects certain dysfunction in obese individuals. PMID:26577934

  3. 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. PMID:27487514

  4. 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. PMID:25816425

  5. 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.

  6. 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

  7. 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

  8. Abdominal obesity and structure and function of the heart in healthy male Koreans: The ARIRANG study.

    PubMed

    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

    2016-09-01

    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 height, 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

  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. Insulin Sensitivity and β-Cell Function Improve after Gastric Bypass in Severely Obese Adolescents

    PubMed Central

    Inge, Thomas H.; Prigeon, Ronald L.; Elder, Deborah A.; Jenkins, Todd M.; Cohen, Robert M.; Xanthakos, Stavra A.; Benoit, Stephen C.; Dolan, Lawrence M.; Daniels, Stephen R.; D’Alessio, David A.

    2016-01-01

    Objective To test the hypothesis that insulin secretion and insulin sensitivity would be improved in adolescents after Roux-en-Y gastric bypass (RYGB). Study design A longitudinal study of 22 adolescents and young adults without diabetes undergoing laparoscopic RYGB (mean age 17.1 ± 1.42 years; range 14.5–20.1; male/female 8/14; Non-Hispanic White/African American 17/5) was conducted. Intravenous glucose tolerance tests were done to obtain insulin sensitivity (insulin sensitivity index), insulin secretion (acute insulin response to glucose), and the disposition index as primary outcome variables. These variables were compared over the 1 year of observation using linear mixed modeling. Results In the 1-year following surgery, body mass index fell by 38% from a mean of 61 ± 12.3 to 39 ± 8.0 kg/m2 (P < .01). Over the year following surgery, fasting glucose and insulin values declined by 54% and 63%, respectively. Insulin sensitivity index increased 300% (P < .01), acute insulin response to glucose decreased 56% (P < .01), leading to a nearly 2-fold increase in the disposition index (P < .01). Consistent with improved β-cell function, the proinsulin to C-peptide ratio decreased by 21% (P < .01). Conclusions RYGB reduced body mass index and improved both insulin sensitivity and β-cell function in severely obese teens and young adults. These findings demonstrate that RYGB is associated with marked metabolic improvements in obese young people even as significant obesity persists. Trial registration ClinicalTrials.gov: NCT00360373. PMID:26363548

  11. Adipose tissue fatty acid chain length and mono-unsaturation increases with obesity and insulin resistance

    PubMed Central

    Yew Tan, Chong; Virtue, Samuel; Murfitt, Steven; Robert, Lee D.; Phua, Yi Hui; Dale, Martin; Griffin, Julian L.; Tinahones, Francisco; Scherer, Philipp E.; Vidal-Puig, Antonio

    2015-01-01

    The non-essential fatty acids, C18:1n9, C16:0, C16:1n7, C18:0 and C18:1n7 account for over 75% of fatty acids in white adipose (WAT) triacylglycerol (TAG). The relative composition of these fatty acids (FA) is influenced by the desaturases, SCD1-4 and the elongase, ELOVL6. In knock-out models, loss of SCD1 or ELOVL6 results in reduced Δ9 desaturated and reduced 18-carbon non-essential FA respectively. Both Elovl6 KO and SCD1 KO mice exhibit improved insulin sensitivity. Here we describe the relationship between WAT TAG composition in obese mouse models and obese humans stratified for insulin resistance. In mouse models with increasing obesity and insulin resistance, there was an increase in scWAT Δ9 desaturated FAs (SCD ratio) and FAs with 18-carbons (Elovl6 ratio) in mice. Data from mouse models discordant for obesity and insulin resistance (AKT2 KO, Adiponectin aP2-transgenic), suggested that scWAT TAG Elovl6 ratio was associated with insulin sensitivity, whereas SCD1 ratio was associated with fat mass. In humans, a greater SCD1 and Elovl6 ratio was found in metabolically more harmful visceral adipose tissue when compared to subcutaneous adipose tissue. PMID:26679101

  12. Gut microbiota as a key player in triggering obesity, systemic inflammation and insulin resistance.

    PubMed

    Escobedo, Galileo; López-Ortiz, Eduardo; Torres-Castro, Israel

    2014-01-01

    Obesity-related systemic inflammation contributes to develop insulin resistance. The main factors involved in the relationship of obesity with systemic inflammation and insulin resistance have not been completely elucidated. Microbiota includes around 1013 to 1014 microbes harboring the human gut, which are clustered in approximately a thousand different bacterial species. Several studies suggest that imbalance in the intestinal bacterial population could result in obesity, systemic inflammation and metabolic dysfunction. Here, we review the main bacterial groups observed in obesity as well as their possible role in increasing the intestinal permeability and lipopolysaccharide-related endotoxemia. Furthermore, we point out the role of intestinal dysbiosis in the inflammatory activation of macrophages with the ability to infiltrate in the visceral adipose tissue and induce insulin resistance. Finally, we discuss the apparent beneficial use of prebiotics and probiotics in ameliorating both systemic inflammation and metabolic dysfunction. Present information may be useful in the future design of novel therapies focused on treating obesity and insulin resistance by restoring the gut microbiota balance.

  13. Obesity and Insulin Resistance Are the Main Determinants of Postprandial Lipoprotein Dysmetabolism in Polycystic Ovary Syndrome

    PubMed Central

    Phelan, Niamh; Boran, Gerard; O'Connor, Anna-Louise; Gibney, James

    2016-01-01

    Postprandial dyslipidaemia may be a plausible mechanism by which polycystic ovary syndrome (PCOS) increases cardiovascular risk. We sought to investigate whether the postprandial glucose and insulin and lipid and lipoprotein responses, including that of apolipoprotein B-48 (apoB-48) containing chylomicrons, to a mixed meal are different in obese PCOS women when compared to obese control subjects and whether differences, if any, are related to obesity, insulin resistance (IR), hyperandrogenaemia, or PCOS status. 26 women with PCOS (age 30.4 ± 1.2 years (mean ± SEM), body mass index (BMI) 36.8 ± 1.5 kg/m2) and 26 non-PCOS subjects (age 34.1 ± 0.9 years, BMI 31.5 ± 1.0 kg/m2) were studied before and up to 8 hours following a standard mixed meal. AUC-triglyceride (AUC-TG) was higher and AUC-high-density lipoprotein (AUC-HDL) lower in PCOS women. These differences were not apparent when BMI was accounted for. Insulin sensitivity (SI), AUC-apoB-48, and AUC-apolipoprotein B (AUC-apoB) were found to be independent predictors of AUC-TG, accounting for 55% of the variance. Only AUC-insulin remained significantly elevated following adjustment for BMI. Obesity related IR explains postprandial hypertriglyceridaemia and hyperinsulinaemic responses. Management of obesity in premenopausal women with PCOS is likely to reduce their cardiovascular risk burden. PMID:26989412

  14. Hemorheological aspects of the metabolic syndrome: markers of insulin resistance, obesity or hyperinsulinemia?

    PubMed

    Brun, Jean-Frederic; Aloulou, Ikram; Varlet-Marie, Emmanuelle

    2004-01-01

    The metabolic syndrome is a major health problem in western countries, due to the deleterious metabolic consequences of sedentarity and rich diet in the large part of the population who exhibits the so-called "thrifty phenotype". This syndrome, which is at high risk for diabetes and atherothrombosis is associated with hemorheologic abnormalities. Initially, insulin resistance was considered as the core of the syndrome. However, it becomes clear that the syndrome is a cluster in which the combined effects of obesity, insulin resistance, and hyperinsulinemia can be inconstantly associated. Thus, we investigated in 157 nondiabetic subjects (53 males and 104 females, age 35.6+/-1.1 yr, mean BMI 29.2+/-0.6 kg/m2) the respective importance of each of these factors. Subjects were divided in 6 groups according to BMI (cut-off point 25 kg/m2) and insulin sensitivity (SI) measured with the minimal model (lowest quartile SI<1.1 min(-1)/(microU/ml) x 10(-4), highest quartile SI>9.5, middle zone between 1.1 and 9.5). Results show that whole blood viscosity at high shear rate is higher in obese subjects (p<0.01). Plasma viscosity is also higher in obese subjects 1.41+/-0.02 vs 1.34+/-0.012 (p<0.01), and, in addition, in lean subjects, is lower when SI is in the upper quartile. RBC rigidity index "Tk" is higher in obese subjects. A worsening effect of insulin resistance (SI<1.1) on Tk is found only in obese subjects. The aggregability index "M1" is increased when SI<1.1 in both obese and nonobese subjects. No clear effect of either SI or obesity on hematocrit is observed. On the whole, obesity and insulin resistance both impair blood rheology by acting on red cell rigidity and plasma viscosity. Whole blood viscosity at high shear rate reflects rather obesity than insulin resistance. Myrenne "M1" aggregation is rather a marker of hyperinsulinemia. Thus, the hemorheologic picture of the metabolic syndrome is far to be only a reflect of insulin resistance alone.

  15. Mitochondrial Respiratory Capacity and Content Are Normal in Young Insulin-Resistant Obese Humans

    PubMed Central

    Fisher-Wellman, Kelsey H.; Weber, Todd M.; Cathey, Brook L.; Brophy, Patricia M.; Gilliam, Laura A.A.; Kane, Constance L.; Maples, Jill M.; Gavin, Timothy P.; Houmard, Joseph A.; Neufer, P. Darrell

    2014-01-01

    Considerable debate exists about whether alterations in mitochondrial respiratory capacity and/or content play a causal role in the development of insulin resistance during obesity. The current study was undertaken to determine whether such alterations are present during the initial stages of insulin resistance in humans. Young (∼23 years) insulin-sensitive lean and insulin-resistant obese men and women were studied. Insulin resistance was confirmed through an intravenous glucose tolerance test. Measures of mitochondrial respiratory capacity and content as well as H2O2 emitting potential and the cellular redox environment were performed in permeabilized myofibers and primary myotubes prepared from vastus lateralis muscle biopsy specimens. No differences in mitochondrial respiratory function or content were observed between lean and obese subjects, despite elevations in H2O2 emission rates and reductions in cellular glutathione. These findings were apparent in permeabilized myofibers as well as in primary myotubes. The results suggest that reductions in mitochondrial respiratory capacity and content are not required for the initial manifestation of peripheral insulin resistance. PMID:23974920

  16. 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.

  17. Green tea catechin consumption enhances exercise-induced abdominal fat loss in overweight and obese adults.

    PubMed

    Maki, Kevin C; Reeves, Matthew S; Farmer, Mildred; Yasunaga, Koichi; Matsuo, Noboru; Katsuragi, Yoshihisa; Komikado, Masanori; Tokimitsu, Ichiro; Wilder, Donna; Jones, Franz; Blumberg, Jeffrey B; Cartwright, Yolanda

    2009-02-01

    This study evaluated the influence of a green tea catechin beverage on body composition and fat distribution in overweight and obese adults during exercise-induced weight loss. Participants (n = 132 with 107 completers) were randomly assigned to receive a beverage containing approximately 625 mg of catechins with 39 mg caffeine or a control beverage (39 mg caffeine, no catechins) for 12 wk. Participants were asked to maintain constant energy intake and engage in >or=180 min/wk moderate intensity exercise, including >or=3 supervised sessions per week. Body composition (dual X-ray absorptiometry), abdominal fat areas (computed tomography), and clinical laboratory tests were measured at baseline and wk 12. There was a trend (P = 0.079) toward greater loss of body weight in the catechin group compared with the control group; least squares mean (95% CI) changes, adjusted for baseline value, age, and sex, were -2.2 (-3.1, -1.3) and -1.0 (-1.9, -0.1) kg, respectively. Percentage changes in fat mass did not differ between the catechin [5.2 (-7.0, -3.4)] and control groups [-3.5 (-5.4, 1.6)] (P = 0.208). However, percentage changes in total abdominal fat area [-7.7 (-11.7, -3.8) vs. -0.3 (-4.4, 3.9); P = 0.013], subcutaneous abdominal fat area [-6.2 (-10.2, -2.2) vs. 0.8 (-3.3, 4.9); P = 0.019], and fasting serum triglycerides (TG) [-11.2 (-18.8, -3.6) vs. 1.9 (-5.9, 9.7); P = 0.023] were greater in the catechin group. These findings suggest that green tea catechin consumption enhances exercise-induced changes in abdominal fat and serum TG.

  18. Adipose tissue macrophages, low grade inflammation and insulin resistance in human obesity.

    PubMed

    Heilbronn, Leonie K; Campbell, Lesley V

    2008-01-01

    Obesity was first described as a low-grade inflammatory condition more than a decade ago. However, it is only relatively recently that obese individuals have been described with increased macrophage infiltration of adipose tissue, as well as an increase in the number of "M1" or "classically activated" macrophages. Furthermore, macrophages have been identified as the primary source of many of the circulating inflammatory molecules that are detected in the obese state and are postulated to be causal both in the development of insulin resistance and in the progression to type 2 diabetes. There is also novel evidence to suggest that macrophages inhibit adipocyte differentiation, potentially leading to adipocyte hypertrophy, altered secretion of adipokines and ectopic storage of lipid within liver, muscle and other non-adipose tissues. Currently, it is not clear what causes increased macrophage infiltration of adipose tissue in obese individuals. Theories include altered signalling by adipocytes, nutritional induction of metabolic endotoxemia or reduced angiogenesis and local adipose cell hypoxia. Importantly, PPAR-gamma agonists have been shown to alter macrophage phenotype to "M2" or an "alternatively activated" anti-inflammatory phenotype and may induce macrophage specific cell death. Consequently, excitement surrounds the potential for specific inhibition of macrophage infiltration of adipose tissue via pharmacotherapy for obese patients and more particularly as adjunct therapy to improve insulin sensitivity in obese individuals with insulin resistance and overt type 2 diabetes.

  19. The relationship between vitamin D status, physical activity and insulin resistance in overweight and obese subjects

    PubMed Central

    Kavadar, Gülis; Demircioğlu, Demet Tekdöş; Özgönenel, Levent; Emre, Tuluhan Yunus

    2015-01-01

    Type 2 diabetes mellitus (T2DM) incidence has been increasing worldwide along with the rise of obesity and sedantery lifestyle. Decreased physical activity (PA) and obesity have also been associated with the low vitamin D levels. We aimed to determine the association between PA, vitamin D status and insulin resistance in overweight and obese subjects. A total of 294 (186 female, 108 male) overweight or obese subjects were included in this cross-sectional study. 25-hydroxy vitamin D (25(OH)D), insulin, fasting plasma glucose (FPG) and HbA1c levels were measured in blood samples. Body mass index (BMI), HOMA-index and total score of International Physical Activity Questionnaire-long form (IPAQ)were calculated. Insulin resistant subjects were compared with the non-resistant group. The mean age of the participants was 45±12.25 and 41.39±10.32; 25(OH)D levels were 8.91 ± 4.30 and 17.62 ± 10.47 ng/dL; BMIs were 31.29 ± 4.48 and 28.2 ± 3.16 kg/m², IPAQ total scores were 548.71±382.81 and 998±486.21 in the insulin resistant and nonresistant subjects, respectively. There was a statistically significant difference in terms of 25(OH)D, FPG, insulin levels, IPAQ total score and BMI between the two groups (p = 0.001, p = 0.001, p = 0.001, p = 0.001, p = 0.001). Significantly low 25(OH)D levels, high BMI and low PA in insulin resistant subjects confirm the importance of active lifestyle and the maintenance of normal vitamin D levels in overweight and obese subjects in prevention of T2DM. PMID:26042515

  20. The impact of insulin resistance and inflammation on the association between sarcopenic obesity and physical functioning.

    PubMed

    Levine, Morgan E; Crimmins, Eileen M

    2012-10-01

    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 (IR(HOMA)) 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

  1. Obesity-induced DNA released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance

    PubMed Central

    Nishimoto, Sachiko; Fukuda, Daiju; Higashikuni, Yasutomi; Tanaka, Kimie; Hirata, Yoichiro; Murata, Chie; Kim-Kaneyama, Joo-ri; Sato, Fukiko; Bando, Masahiro; Yagi, Shusuke; Soeki, Takeshi; Hayashi, Tetsuya; Imoto, Issei; Sakaue, Hiroshi; Shimabukuro, Michio; Sata, Masataka

    2016-01-01

    Obesity stimulates chronic inflammation in adipose tissue, which is associated with insulin resistance, although the underlying mechanism remains largely unknown. Here we showed that obesity-related adipocyte degeneration causes release of cell-free DNA (cfDNA), which promotes macrophage accumulation in adipose tissue via Toll-like receptor 9 (TLR9), originally known as a sensor of exogenous DNA fragments. Fat-fed obese wild-type mice showed increased release of cfDNA, as determined by the concentrations of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) in plasma. cfDNA released from degenerated adipocytes promoted monocyte chemoattractant protein-1 (MCP-1) expression in wild-type macrophages, but not in TLR9-deficient (Tlr9−/−) macrophages. Fat-fed Tlr9−/− mice demonstrated reduced macrophage accumulation and inflammation in adipose tissue and better insulin sensitivity compared with wild-type mice, whereas bone marrow reconstitution with wild-type bone marrow restored the attenuation of insulin resistance observed in fat-fed Tlr9−/− mice. Administration of a TLR9 inhibitory oligonucleotide to fat-fed wild-type mice reduced the accumulation of macrophages in adipose tissue and improved insulin resistance. Furthermore, in humans, plasma ssDNA level was significantly higher in patients with computed tomography–determined visceral obesity and was associated with homeostasis model assessment of insulin resistance (HOMA-IR), which is the index of insulin resistance. Our study may provide a novel mechanism for the development of sterile inflammation in adipose tissue and a potential therapeutic target for insulin resistance. PMID:27051864

  2. 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.

  3. mRNA expression of diacylglycerol kinase isoforms in insulin-sensitive tissues: effects of obesity and insulin resistance.

    PubMed

    Mannerås-Holm, Louise; Kirchner, Henriette; Björnholm, Marie; Chibalin, Alexander V; Zierath, Juleen R

    2015-04-01

    Diacylglycerol kinase (DGK) isoforms regulate signal transduction and lipid metabolism. DGKδ deficiency leads to hyperglycemia, peripheral insulin resistance, and metabolic inflexibility. Thus, dysregulation of other DGK isoforms may play a role in metabolic dysfunction. We investigated DGK isoform mRNA expression in extensor digitorum longus (EDL) and soleus muscle, liver as well as subcutaneous and epididymal adipose tissue in C57BL/6J mice and obese and insulin-resistant ob/ob mice. All DGK isoforms, except for DGKκ, were detectable, although with varying mRNA expression. Liver DGK expression was generally lowest, with several isoforms undetectable. In soleus muscle, subcutaneous and epididymal adipose tissue, DGKδ was the most abundant isoform. In EDL muscle, DGKα and DGKζ were the most abundant isoforms. In liver, DGKζ was the most abundant isoform. Comparing obese insulin-resistant ob/ob mice to lean C57BL/6J mice, DGKβ, DGKι, and DGKθ were increased and DGKε expression was decreased in EDL muscle, while DGKβ, DGKη and DGKθ were decreased and DGKδ and DGKι were increased in soleus muscle. In liver, DGKδ and DGKζ expression was increased in ob/ob mice. DGKη was increased in subcutaneous fat, while DGKζ was increased and DGKβ, DGKδ, DGKη and DGKε were decreased in epididymal fat from ob/ob mice. In both adipose tissue depots, DGKα and DGKγ were decreased and DGKι was increased in ob/ob mice. In conclusion, DGK mRNA expression is altered in an isoform- and tissue-dependent manner in obese insulin-resistant ob/ob mice. DGK isoforms likely have divergent functional roles in distinct tissues, which may contribute to metabolic dysfunction. PMID:25847921

  4. IKKε is key to induction of insulin resistance in the hypothalamus, and its inhibition reverses obesity.

    PubMed

    Weissmann, Laís; Quaresma, Paula G F; Santos, Andressa C; de Matos, Alexandre H B; Pascoal, Vínicius D'Ávila Bittencourt; Zanotto, Tamires M; Castro, Gisele; Guadagnini, Dioze; da Silva, Joelcimar Martins; Velloso, Licio A; Bittencourt, Jackson C; Lopes-Cendes, Iscia; Saad, Mario J A; Prada, Patricia O

    2014-10-01

    IKK epsilon (IKKε) is induced by the activation of nuclear factor-κB (NF-κB). Whole-body IKKε knockout mice on a high-fat diet (HFD) were protected from insulin resistance and showed altered energy balance. We demonstrate that IKKε is expressed in neurons and is upregulated in the hypothalamus of obese mice, contributing to insulin and leptin resistance. Blocking IKKε in the hypothalamus of obese mice with CAYMAN10576 or small interfering RNA decreased NF-κB activation in this tissue, relieving the inflammatory environment. Inhibition of IKKε activity, but not TBK1, reduced IRS-1(Ser307) phosphorylation and insulin and leptin resistance by an improvement of the IR/IRS-1/Akt and JAK2/STAT3 pathways in the hypothalamus. These improvements were independent of body weight and food intake. Increased insulin and leptin action/signaling in the hypothalamus may contribute to a decrease in adiposity and hypophagia and an enhancement of energy expenditure accompanied by lower NPY and increased POMC mRNA levels. Improvement of hypothalamic insulin action decreases fasting glycemia, glycemia after pyruvate injection, and PEPCK protein expression in the liver of HFD-fed and db/db mice, suggesting a reduction in hepatic glucose production. We suggest that IKKε may be a key inflammatory mediator in the hypothalamus of obese mice, and its hypothalamic inhibition improves energy and glucose metabolism.

  5. Quantification of Abdominal Fat Depots in Rats and Mice during Obesity and Weight Loss Interventions

    PubMed Central

    KN, Bhanu Prakash; Gopalan, Venkatesh; Lee, Swee Shean; Velan, S. Sendhil

    2014-01-01

    Background & Aims Obesity is a leading healthcare issue contributing to metabolic diseases. There is a great interest in non-invasive approaches for quantitating abdominal fat in obese animals and humans. In this work, we propose an automated method to distinguish and quantify subcutaneous and visceral adipose tissues (SAT and VAT) in rodents during obesity and weight loss interventions. We have also investigated the influence of different magnetic resonance sequences and sources of variability in quantification of fat depots. Materials and Methods High-fat diet fed rodents were utilized for investigating the changes during obesity, exercise, and calorie restriction interventions (N = 7/cohort). Imaging was performed on a 7T Bruker ClinScan scanner using fast spin echo (FSE) and Dixon imaging methods to estimate the fat depots. Finally, we quantified the SAT and VAT volumes between the L1–L5 lumbar vertebrae using the proposed automatic hybrid geodesic region-based curve evolution algorithm. Results Significant changes in SAT and VAT volumes (p<0.01) were observed between the pre- and post-intervention measurements. The SAT and VAT were 44.22±9%, 21.06±1.35% for control, −17.33±3.07%, −15.09±1.11% for exercise, and 18.56±2.05%, −3.9±0.96% for calorie restriction cohorts, respectively. The fat quantification correlation between FSE (with and without water suppression) sequences and Dixon for SAT and VAT were 0.9709, 0.9803 and 0.9955, 0.9840 respectively. The algorithm significantly reduced the computation time from 100 sec/slice to 25 sec/slice. The pre-processing, data-derived contour placement and avoidance of strong background–image boundary improved the convergence accuracy of the proposed algorithm. Conclusions We developed a fully automatic segmentation algorithm to quantitate SAT and VAT from abdominal images of rodents, which can support large cohort studies. We additionally identified the influence of non-algorithmic variables including

  6. 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.

  7. 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.

  8. 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.

  9. Evidence for Threshold Effects of 25-Hydroxyvitamin D on Glucose Tolerance and Insulin Resistance in Black and White Obese Postmenopausal Women12

    PubMed Central

    Sorkin, John D.; Vasaitis, Tadas Sean; Streeten, Elizabeth; Ryan, Alice S.; Goldberg, Andrew P.

    2014-01-01

    We identified normal vs. abnormal 25-hydroxyvitamin D [25(OH)D] concentrations by examining the relation of 25(OH)D to non-bone–related measures (plasma glucose, insulin resistance, lipids, blood pressure, fitness, obesity, and regional adiposity) and asking whether there is a 25(OH)D concentration above and below which the relation between 25(OH)D and outcome changes. We examined the relation between 25(OH)D and outcome by race to see whether race-specific normal ranges are needed, and we examined the role of insulin-like growth factor-1 (IGF-1) in modulating the relation between 25(OH)D and outcome. In a cross-sectional study of 239 overweight and obese, sedentary postmenopausal women without diabetes (83 black, 156 white), outcome measures included plasma lipids, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), IGF-1, parathyroid hormone (PTH), aerobic fitness, body composition, subcutaneous abdominal and visceral fat, and blood pressure. We identified threshold effects in the association between 25(OH)D and these variables using piecewise linear regressions. We found that 25(OH)D was inversely related to fasting glucose, fasting and 2-h insulin, HOMA-IR, visceral abdominal fat, percentage fat, PTH, and triglycerides. Evidence for a threshold effect of 25(OH)D was found for 2-h glucose, 2-h insulin, fasting insulin, and HOMA-IR. There was no evidence suggesting the need for race-specific normal 25(OH)D concentrations. IGF-1 modulated the relation between 25(OH)D and outcome but only below, and not above, a threshold 25(OH)D concentration. Our findings suggest a threshold effect of 25(OH)D on glucose–insulin metabolism such that 25(OH)D ≥ ∼26 μg/L (65.0 pmol/L) supports normal glucose homeostasis and that the same cut point defining normal 25(OH)D concentration can be used in black and white women. This study was registered at clinicaltrials.gov as NCT01798030. PMID:24717362

  10. Glucose-6-Phosphate Dehydrogenase Deficiency Improves Insulin Resistance With Reduced Adipose Tissue Inflammation in Obesity.

    PubMed

    Ham, Mira; Choe, Sung Sik; Shin, Kyung Cheul; Choi, Goun; Kim, Ji-Won; Noh, Jung-Ran; Kim, Yong-Hoon; Ryu, Je-Won; Yoon, Kun-Ho; Lee, Chul-Ho; Kim, Jae Bum

    2016-09-01

    Glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme of the pentose phosphate pathway, plays important roles in redox regulation and de novo lipogenesis. It was recently demonstrated that aberrant upregulation of G6PD in obese adipose tissue mediates insulin resistance as a result of imbalanced energy metabolism and oxidative stress. It remains elusive, however, whether inhibition of G6PD in vivo may relieve obesity-induced insulin resistance. In this study we showed that a hematopoietic G6PD defect alleviates insulin resistance in obesity, accompanied by reduced adipose tissue inflammation. Compared with wild-type littermates, G6PD-deficient mutant (G6PD(mut)) mice were glucose tolerant upon high-fat-diet (HFD) feeding. Intriguingly, the expression of NADPH oxidase genes to produce reactive oxygen species was alleviated, whereas that of antioxidant genes was enhanced in the adipose tissue of HFD-fed G6PD(mut) mice. In diet-induced obesity (DIO), the adipose tissue of G6PD(mut) mice decreased the expression of inflammatory cytokines, accompanied by downregulated proinflammatory macrophages. Accordingly, macrophages from G6PD(mut) mice greatly suppressed lipopolysaccharide-induced proinflammatory signaling cascades, leading to enhanced insulin sensitivity in adipocytes and hepatocytes. Furthermore, adoptive transfer of G6PD(mut) bone marrow to wild-type mice attenuated adipose tissue inflammation and improved glucose tolerance in DIO. Collectively, these data suggest that inhibition of macrophage G6PD would ameliorate insulin resistance in obesity through suppression of proinflammatory responses. PMID:27284106

  11. Association Between Duration of Overall and Abdominal Obesity Beginning in Young Adulthood and Coronary Artery Calcification in Middle Age

    PubMed Central

    Reis, Jared P.; Loria, Catherine M.; Lewis, Cora E.; Powell-Wiley, Tiffany M.; Wei, Gina S.; Carr, J. Jeffrey; Terry, James G.; Liu, Kiang

    2014-01-01

    IMPORTANCE Younger individuals are experiencing a greater cumulative exposure to excess adiposity over their lifetime. However, few studies have determined the consequences of long-term obesity. OBJECTIVE To examine whether the duration of overall and abdominal obesity was associated with the presence and 10-year progression of coronary artery calcification (CAC), a subclinical predictor of coronary heart disease. DESIGN, SETTING, AND PARTICIPANTS Prospective study of 3275 white and black adults aged 18 to 30 years at baseline in 1985–1986 who did not initially have overall obesity (body mass index [BMI] ≥30) or abdominal obesity (men: waist circumference [WC] >102 cm; women: >88 cm) in the multicenter, community-based Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants completed computed tomography scanning for the presence of CAC during the 15-, 20-, or 25-year follow-up examinations. Duration of overall and abdominal obesity was calculated using repeat measurements of BMI and WC, respectively, performed 2, 5, 7, 10, 15, 20, and 25 years after baseline. MAIN OUTCOMES AND MEASURES Presence of CAC was measured by computed tomography at the year 15 (2000–2001), year 20 (2005–2006), or year 25 (2010–2011) follow-up examinations. Ten-year progression of CAC (2000–2001 to 2010–2011) was defined as incident CAC in 2010–2011 or an increase in CAC score of 20 Agatston units or greater. RESULTS During follow-up, 40.4% and 41.0% developed overall and abdominal obesity, respectively. Rates of CAC per 1000 person-years were higher for those who experienced more than 20 years vs 0 years of overall obesity (16.0 vs 11.0, respectively) and abdominal obesity (16.7 vs 11.0). Approximately 25.2% and 27.7% of those with more than 20 years of overall and abdominal obesity, respectively, experienced progression of CAC vs 20.2% and 19.5% of those with 0 years. After adjustment for BMI or WC and potential confounders, the hazard ratios for CAC

  12. Serum Autotaxin/ENPP2 Correlates with Insulin Resistance in Older Humans with Obesity

    PubMed Central

    Reeves, Valerie L.; Trybula, Joy S.; Wills, Rachel C.; Goodpaster, Bret H.; Dubé, John J.; Kienesberger, Petra C.; Kershaw, Erin E.

    2015-01-01

    Objective Autotaxin (ATX) is an adipocyte-derived lysophospholipase D that generates the lipid signaling molecule lysophosphatidic acid (LPA). The ATX/LPA pathway in adipose tissue has recently been implicated in obesity and insulin resistance in animal models, but the role of circulating ATX in humans remains unclear. The aim of the present study was to determine the relationship between serum ATX and insulin resistance. Methods In this retrospective study, older (60–75 years), non-diabetic human participants with overweight or obesity (BMI 25–37 kg/m2), were characterized for metabolic phenotype including measures of energy, glucose, and lipid homeostasis. The relationship between serum ATX and metabolic parameters was then determined using correlative and predictive statistics. Results Serum ATX was higher in females than in males. After controlling for sex, serum ATX correlated with multiple measures of adiposity and glucose homeostasis/insulin action. Serum ATX and BMI also independently predicted glucose infusion rate during a hyperinsulinemic euglycemic clamp and homeostatic model assessment of insulin resistance after controlling for sex and medication use. Conclusion Serum ATX correlates with and predicts measures of glucose homeostasis and insulin sensitivity in older humans, suggesting that it may be a potential pathogenic factor and/or diagnostic/therapeutic target for insulin resistance in this population. PMID:26727116

  13. Anti-obesity and anti-insulin resistance effects of tomato vinegar beverage in diet-induced obese mice.

    PubMed

    Seo, Kwon-Il; Lee, Jin; Choi, Ra-Yeong; Lee, Hae-In; Lee, Ju-Hye; Jeong, Yong-Ki; Kim, Myung-Joo; Lee, Mi-Kyung

    2014-07-25

    This study investigated the mechanism of processed tomato vinegar beverage (TVB)-mediated anti-obesity and anti-insulin resistance effects in high-fat diet (HF)-induced obese mice. Oral administration of TVB (14 mL kg(-1) body weight) to HF-fed mice for 6 weeks effectively reduced the body and visceral fat weight and significantly lowered plasma free fatty acid, triglyceride and hepatic triglyceride levels. TVB significantly increased fecal triglyceride excretion, both phosphorylated AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) and peroxisome proliferator-activated receptor (PPAR)α protein levels in the liver, which were associated with increased fatty acid β-oxidation and carnitine palmitoyltransferase activities in HF-fed mice. TVB improved glucose tolerance, hyperinsulinemia and HOMA-IR levels in the HF + TVB group compared to the HF group. Additionally, TVB significantly increased glucokinase activity and decreased glucose-6-phosphatase activity in the liver, which enhanced glucose metabolism in obese mice. These results suggest that TVB prevents visceral obesity and insulin resistance via AMPK/PPARα-mediated fatty acid and glucose oxidation. PMID:24867606

  14. The AMPK activator R419 improves exercise capacity and skeletal muscle insulin sensitivity in obese mice

    PubMed Central

    Marcinko, Katarina; Bujak, Adam L.; Lally, James S.V.; Ford, Rebecca J.; Wong, Tammy H.; Smith, Brennan K.; Kemp, Bruce E.; Jenkins, Yonchu; Li, Wei; Kinsella, Todd M.; Hitoshi, Yasumichi; Steinberg, Gregory R.

    2015-01-01

    Objective Skeletal muscle AMP-activated protein kinase (AMPK) is important for regulating glucose homeostasis, mitochondrial content and exercise capacity. R419 is a mitochondrial complex-I inhibitor that has recently been shown to acutely activate AMPK in myotubes. Our main objective was to examine whether R419 treatment improves insulin sensitivity and exercise capacity in obese insulin resistant mice and whether skeletal muscle AMPK was important for mediating potential effects. Methods Glucose homeostasis, insulin sensitivity, exercise capacity, and electron transport chain content/activity were examined in wildtype (WT) and AMPK β1β2 muscle-specific null (AMPK-MKO) mice fed a high-fat diet (HFD) with or without R419 supplementation. Results There was no change in weight gain, adiposity, glucose tolerance or insulin sensitivity between HFD-fed WT and AMPK-MKO mice. In both HFD-fed WT and AMPK-MKO mice, R419 enhanced insulin tolerance, insulin-stimulated glucose disposal, skeletal muscle 2-deoxyglucose uptake, Akt phosphorylation and glucose transporter 4 (GLUT4) content independently of alterations in body mass. In WT, but not AMPK-MKO mice, R419 improved treadmill running capacity. Treatment with R419 increased muscle electron transport chain content and activity in WT mice; effects which were blunted in AMPK-MKO mice. Conclusions Treatment of obese mice with R419 improved skeletal muscle insulin sensitivity through a mechanism that is independent of skeletal muscle AMPK. R419 also increases exercise capacity and improves mitochondrial function in obese WT mice; effects that are diminished in the absence of skeletal muscle AMPK. These findings suggest that R419 may be a promising therapy for improving whole-body glucose homeostasis and exercise capacity. PMID:26413470

  15. 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.

  16. 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

  17. 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

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

    PubMed

    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

  19. 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

  20. Aerobic exercise but not resistance exercise reduces intrahepatic lipid content and visceral fat and improves insulin sensitivity in obese adolescent girls: a randomized controlled trial.

    PubMed

    Lee, SoJung; Deldin, Anthony R; White, David; Kim, YoonMyung; Libman, Ingrid; Rivera-Vega, Michelle; Kuk, Jennifer L; Sandoval, Sandra; Boesch, Chris; Arslanian, Silva

    2013-11-15

    It is unclear whether regular exercise alone (no caloric restriction) is a useful strategy to reduce adiposity and obesity-related metabolic risk factors in obese girls. We examined the effects of aerobic (AE) vs. resistance exercise (RE) alone on visceral adipose tissue (VAT), intrahepatic lipid, and insulin sensitivity in obese girls. Forty-four obese adolescent girls (BMI ≥95th percentile, 12-18 yr) with abdominal obesity (waist circumference 106.5 ± 11.1 cm) were randomized to 3 mo of 180 min/wk AE (n = 16) or RE (n = 16) or a nonexercising control group (n = 12). Total fat and VAT were assessed by MRI and intrahepatic lipid by proton magnetic resonance spectroscopy. Intermuscular AT (IMAT) was measured by CT. Insulin sensitivity was evaluated by a 3-h hyperinsulinemic (80 mU·m(2)·min(-1)) euglycemic clamp. Compared with controls (0.13 ± 1.10 kg), body weight did not change (P > 0.1) in the AE (-1.31 ± 1.43 kg) and RE (-0.31 ± 1.38 kg) groups. Despite the absence of weight loss, total body fat (%) and IMAT decreased (P < 0.05) in both exercise groups compared with control. Compared with control, significant (P < 0.05) reductions in VAT (Δ-15.68 ± 7.64 cm(2)) and intrahepatic lipid (Δ-1.70 ± 0.74%) and improvement in insulin sensitivity (Δ0.92 ± 0.27 mg·kg(-1)·min(-1) per μU/ml) were observed in the AE group but not the RE group. Improvements in insulin sensitivity in the AE group were associated with the reductions in total AT mass (r = -0.65, P = 0.02). In obese adolescent girls, AE but not RE is effective in reducing liver fat and visceral adiposity and improving insulin sensitivity independent of weight loss or calorie restriction.

  1. Prevalence of General and Abdominal Obesity in a Nationally Representative Sample of Iranian Children and Adolescents: The CASPIAN-IV Study

    PubMed Central

    Esmaili, Haleh; Bahreynian, Maryam; Qorbani, Mostafa; Motlagh, Mohammad Esmaeel; Ardalan, Gelayol; Heshmat, Ramin; Kelishadi, Roya

    2015-01-01

    Background: Pediatric obesity is one of the predisposing risk factors for many non-communicable diseases. Objectives: The purpose of this study was to estimate the national prevalence of general and abdominal obesity among Iranian children and adolescents. Patients and Methods: This cross-sectional nation-wide study was performed in 30 provinces in Iran among 14880 school students aged 6 – 18 years, selected by multistage random cluster sampling. The World Health Organization growth curve was used to categorize Body Mass Index (BMI). Obesity was defined as BMI equal to or higher than the age- and gender-specific 95th percentile; abdominal obesity was considered as waist-to-height ratio of more than 0.5. Results: Data of 13486 out of 14880 invited students were complete (response rate of 90.6%). They consisted of 6543 girls and 75.6% urban residents, and had a mean age of 12.45 (95% CI: 12.40 - 12.51) years. The prevalence rate of general and abdominal obesity was 11.89% (13.58% of boys vs. 10.15% of girls) and 19.12% (20.41% of boys vs. 17.79% of girls), respectively. The highest frequency of obesity was found in the middle school students (13.87% general and 20.84% abdominal obesity). The highest prevalence of general obesity was found in Boushehr (19%) followed by Guilan and Mazandaran (18.3%, 18.3%), while the lowest prevalence was observed in Hormozgan (2.6%). The highest frequency of abdominal obesity was found in Mazandaran (30.2%), Ardabil (29.2%) and Tehran (27.9%). Provinces such as Sistan-Baloochestan (8.4%), Hormozagan (7.4%), and Kerman (11.4%) had the lowest prevalence of abdominal obesity. The Southern and South Eastern provinces had the lowest prevalence of general obesity (2.6% and 5.6%) and abdominal obesity (7.4% and 8.8%). Moreover, the highest prevalence of obesity was found in North and North West Iran by maximum frequency of 18.3% general obesity and 30.2% of abdominal obesity. Conclusions: The results showed a high prevalence of general and

  2. Arginine and glutamine availability and macrophage functions in the obese insulin-resistant Zucker rat.

    PubMed

    Blanc, Marie-Céline; Moinard, Christophe; Béziel, Aurélie; Darquy, Sylviane; Cynober, Luc; De Bandt, Jean-Pascal

    2005-01-01

    Increased susceptibility to infections in obese patients may be related to decreased availability of arginine and glutamine, which may affect immune cell functions. Our aim was to evaluate the in vitro effects of these amino acids on the function of macrophages from obese insulin-resistant Zucker rats. Macrophages, isolated from male Zucker obese or lean rats by peritoneal lavage, were incubated in Dulbecco's modified Eagle medium (DMEM) without arginine or glutamine. Arginine or glutamine was added to the medium at increasing final concentrations (0, 0.25, 0.5, 1 or 2 mM). After stimulation by lipopolysaccharide (LPS) from E. coli (40 microg/ml), productions of tumour necrosis factor alpha (TNFalpha) and of nitric oxide (NO) were measured after 3 or 48 h incubation, respectively. NO production, lower in macrophages from obese rats, decreased in macrophages from lean rats (0 mM: 2,423 +/- 1,174 vs. 2 mM: 198 +/- 31 microM/mg protein/24 h; P < 0.05), but not in those from obese rats, when glutamine was added. TNFalpha production, lower in macrophages from obese rats, was inversely correlated with glutamine concentration. In the presence of arginine, NO production was constantly higher in macrophages from obese rats. It peaked at 0.5 mM arginine and decreased thereafter in both groups. TNFalpha production in macrophages from lean rats was unaffected by arginine, but decreased in macrophages from obese rats (0 mM: 1920 +/- 450 vs. 2 mM: 810 +/- 90 microM/mg protein/3 h; P < 0.05). These results suggest that abnormalities in cell signalling or in arginine and glutamine metabolism in macrophages of obese rats, resulting in decreased TNFalpha production and increased NO release, may contribute to increased susceptibility to infection in insulin-resistant states.

  3. [Molecular mechanisms and correlations of insulin resistance, obesity, and type 2 diabetes mellitus].

    PubMed

    Winkler, Gábor; Cseh, Károly

    2009-04-26

    Adipose tissue cells express and secrete numerous proteins influencing the signal transduction pathways of insulin receptor by auto-, para- and endocrine manner. Several cytokines, tumor necrosis factor-alpha and its soluble receptor forms, sTNFR1 and sTNFR2, resistin, retinol-binding protein 4, plasminogen activator inhibitor, lipocain 1 inhibit the signalization of insulin receptor causing insulin resistance in target tissues, mainly in adipose, liver and muscle, brain, endothelial as well as in pancreatic beta-cells. However, many other proteins produced by the fat tissue, such as adiponectin, visfatin, vaspin, apelin, omentin and chemerin enhance the signal transmission of the receptor. Recently discovered common mechanisms leading to insulin and cytokine resistance in obesity and type 2 diabetes mellitus, e.g. protein family of suppressor of cytokine signaling (SOCS) are also discussed. PMID:19362933

  4. 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.

  5. Protein malnutrition potentiates the amplifying pathway of insulin secretion in adult obese mice.

    PubMed

    Leite, Nayara Carvalho; de Paula, Flávia; Borck, Patrícia Cristine; Vettorazzi, Jean Franciesco; Branco, Renato Chaves Souto; Lubaczeuski, Camila; Boschero, Antonio Carlos; Zoppi, Claudio Cesar; Carneiro, Everardo Magalhães

    2016-01-01

    Pancreatic beta cell (β) dysfunction is an outcome of malnutrition. We assessed the role of the amplifying pathway (AMP PATH) in β cells in malnourished obese mice. C57Bl-6 mice were fed a control (C) or a low-protein diet (R). The groups were then fed a high-fat diet (CH and RH). AMP PATH contribution to insulin secretion was assessed upon incubating islets with diazoxide and KCl. CH and RH displayed increased glucose intolerance, insulin resistance and glucose-stimulated insulin secretion. Only RH showed a higher contribution of the AMP PATH. The mitochondrial membrane potential of RH was decreased, and ATP flux was unaltered. In RH islets, glutamate dehydrogenase (GDH) protein content and activity increased, and the AMP PATH contribution was reestablished when GDH was blunted. Thus, protein malnutrition induces mitochondrial dysfunction in β cells, leading to an increased contribution of the AMP PATH to insulin secretion through the enhancement of GDH content and activity.

  6. Protein malnutrition potentiates the amplifying pathway of insulin secretion in adult obese mice

    PubMed Central

    Leite, Nayara Carvalho; de Paula, Flávia; Borck, Patrícia Cristine; Vettorazzi, Jean Franciesco; Branco, Renato Chaves Souto; Lubaczeuski, Camila; Boschero, Antonio Carlos; Zoppi, Claudio Cesar; Carneiro, Everardo Magalhães

    2016-01-01

    Pancreatic beta cell (β) dysfunction is an outcome of malnutrition. We assessed the role of the amplifying pathway (AMP PATH) in β cells in malnourished obese mice. C57Bl-6 mice were fed a control (C) or a low-protein diet (R). The groups were then fed a high-fat diet (CH and RH). AMP PATH contribution to insulin secretion was assessed upon incubating islets with diazoxide and KCl. CH and RH displayed increased glucose intolerance, insulin resistance and glucose-stimulated insulin secretion. Only RH showed a higher contribution of the AMP PATH. The mitochondrial membrane potential of RH was decreased, and ATP flux was unaltered. In RH islets, glutamate dehydrogenase (GDH) protein content and activity increased, and the AMP PATH contribution was reestablished when GDH was blunted. Thus, protein malnutrition induces mitochondrial dysfunction in β cells, leading to an increased contribution of the AMP PATH to insulin secretion through the enhancement of GDH content and activity. PMID:27633083

  7. Protein malnutrition potentiates the amplifying pathway of insulin secretion in adult obese mice.

    PubMed

    Leite, Nayara Carvalho; de Paula, Flávia; Borck, Patrícia Cristine; Vettorazzi, Jean Franciesco; Branco, Renato Chaves Souto; Lubaczeuski, Camila; Boschero, Antonio Carlos; Zoppi, Claudio Cesar; Carneiro, Everardo Magalhães

    2016-01-01

    Pancreatic beta cell (β) dysfunction is an outcome of malnutrition. We assessed the role of the amplifying pathway (AMP PATH) in β cells in malnourished obese mice. C57Bl-6 mice were fed a control (C) or a low-protein diet (R). The groups were then fed a high-fat diet (CH and RH). AMP PATH contribution to insulin secretion was assessed upon incubating islets with diazoxide and KCl. CH and RH displayed increased glucose intolerance, insulin resistance and glucose-stimulated insulin secretion. Only RH showed a higher contribution of the AMP PATH. The mitochondrial membrane potential of RH was decreased, and ATP flux was unaltered. In RH islets, glutamate dehydrogenase (GDH) protein content and activity increased, and the AMP PATH contribution was reestablished when GDH was blunted. Thus, protein malnutrition induces mitochondrial dysfunction in β cells, leading to an increased contribution of the AMP PATH to insulin secretion through the enhancement of GDH content and activity. PMID:27633083

  8. Obesity and cancer risk: the role of the insulin-IGF axis.

    PubMed

    Renehan, Andrew G; Frystyk, Jan; Flyvbjerg, Allan

    2006-10-01

    Accumulating epidemiological evidence shows that being either overweight or obese, in other words having excess body weight (EBW), is associated with an increased risk of several, common, adult cancers. The molecular mechanisms that underlie these associations are not understood fully, but insulin resistance is likely to be important. The insulin-cancer hypothesis postulates that chronic hyperinsulinemia is associated with decreased concentrations of insulin-like growth factor binding protein1 (IGFBP-1) and IGFBP-2, leading to increased availability of IGF-I and concomitant changes in the cellular environment that favor tumor formation. However, the situation is likely to be more complex because hyperinsulinemia is also associated with alterations in related molecular systems (e.g. sex steroids and adipocytokines). As the prevalence of EBW increases to epidemic proportions, untangling the links between EBW and the insulin-IGF axis and its wider molecular interactions will become increasingly important in the development of preventive strategies.

  9. Establishing abdominal height cut-offs and their association with conventional indices of obesity among Arab children and adolescents

    PubMed Central

    Al-Daghri, Nasser; Alokail, Majed; Al-Attas, Omar; Sabico, Shaun; Kumar, Sudhesh

    2010-01-01

    BACKGROUND AND OBJECTIVES: Obesity, particularly childhood obesity is common in the Middle East, but no studies have examined the relationship of sagittal abdominal diameter (SAD) or abdominal height to conventional markers of obesity in this region. This is the first study to document the association of SAD with measures of obesity among Arab children and adolescents. METHODS: Nine hundred sixty-four Saudi children aged 5-17 years (365 prepubertal, including 146 boys and 219 girls; 249 pubertal, including 125 boys and 124 girls; and 350 postpubertal, including 198 boys and 152 girls) were included in this cross-sectional study. RESULTS: SAD was significantly correlated with indices of obesity regardless of gender, but was strongest among pubertal boys. The cut-off values were as follows: for prepubertal children, 14 cm (equivalent to 50th percentile among girls and 60th percentile among boys); for pubertal children, 15 cm for girls (30th percentile) and 16 cm for boys (50th percentile), and for postpubertal, 21.5 cm for girls (70th percentile) and 22 cm for boys (80th percentile). CONCLUSION: SAD is a reliable indicator of visceral obesity among Arab children and adolescents in particular. Prospective studies should be done to determine whether such an association translates to a promising risk factor for hard endpoints such as diabetes mellitus and coronary heart disease. PMID:20427937

  10. Influence of reversible obesity on eating behavior, blood glucose, and insulin in the rat.

    PubMed

    Steffens, A B

    1975-06-01

    Excessive food intake, resulting in extreme obesity, was induced in rats by electrical stimulation (three 30-min sessions per day for 3 wk) of the lateral hypothalamus (LH). Outside the stimulation sessions no voluntary food intake occurred duringthese weeks. In the subsequent recovery period, accurate records of spontaneous feeding were made. Blood levels of glucose, insulin, and free fatty acids (FFA)were determined during the stimulation period as well as the recovery period. Duringfeeding elicited by electrical stimulation of the LH in the obese phase, there was alarge increase in the glucose level. The insulin level, very high in the intervals between the stimulation sessions, showed no change, a small decline, or a large decrease,respectively, during stimulation in the morning, the afternoon, or the night. If food was withheld during stimulation, there was a large increase in the glucose level and alarge decrease in the insulin level. The first spontaneous meal after the termination of stimulation was extremely postponed, viz, until the glucose and insulin levels returned to normal for the first time. The insulin response to the first spontaneous mealwas exaggerated. Although in the following period (about 10 days) a rapid decrease inbody weight occurred, food intake was only minimal. The insulin level was high and the glucose levelsubnormal during that period. The insulin and glucose levels were normal again only after recovery of normal body weight and food intake. It is tentatively concluded that the regulation of body energy stores (body weight) is achieved through the control of food intake by circulating insulin and glucose levels.

  11. Diet, insulin resistance, and obesity: zoning in on data for Atkins dieters living in South Beach.

    PubMed

    Lara-Castro, Cristina; Garvey, W Timothy

    2004-09-01

    Insulin resistance is a central pathogenic factor for the metabolic syndrome and is associated with both generalized obesity and the accumulation of fat in the omental and intramyocellular compartments. In the context of the current obesity epidemic, it is imperative to consider diets in terms of their ability to both promote weight loss and ameliorate insulin resistance. Weight loss under any dietary formulation depends on hypocaloric intake, and only moderate weight loss (5-10%) is sufficient to augment insulin sensitivity. However, increments in insulin sensitivity may be more directly related to loss of intramyocellular or omental fat rather than loss of total body weight per se. The widespread acceptance of popular low-carbohydrate high-fat diets (e.g. Atkins Diet, Zone Diet, South Beach diet) further underscores the need to evaluate dietary interventions regarding their safety and metabolic effects. These high-fat diets have been shown to be safe in the short term; however, their long-term safety has not been established. With respect to insulin sensitivity, diets enriched in saturated fats can induce insulin resistance, whereas fat substitution with monounsaturated fats can enhance insulin sensitivity. On the other hand, high-fiber, high-carbohydrate diets comprised of foods with low caloric density can similarly be used for effective weight reduction and to ameliorate insulin resistance. Although some data suggest that low-glycemic index diets are most advantageous in this regard, these effects may have more to do with increments in dietary fiber than differences in available carbohydrates. Popular low-carbohydrate, high-fat diets are being fervently embraced as an alternative to challenging modifications in lifestyle and intentional calorie reduction. Current data do not support such unbridled enthusiasm for these diets, particularly in relationship to high-fiber, high-carbohydrate diets emphasizing intake of fresh vegetables and fruits. Long-term studies

  12. Adipose Natural Killer Cells Regulate Adipose Tissue Macrophages to Promote Insulin Resistance in Obesity.

    PubMed

    Lee, Byung-Cheol; Kim, Myung-Sunny; Pae, Munkyong; Yamamoto, Yasuhiko; Eberlé, Delphine; Shimada, Takeshi; Kamei, Nozomu; Park, Hee-Sook; Sasorith, Souphatta; Woo, Ju Rang; You, Jia; Mosher, William; Brady, Hugh J M; Shoelson, Steven E; Lee, Jongsoon

    2016-04-12

    Obesity-induced inflammation mediated by immune cells in adipose tissue appears to participate in the pathogenesis of insulin resistance. We show that natural killer (NK) cells in adipose tissue play an important role. High-fat diet (HFD) increases NK cell numbers and the production of proinflammatory cytokines, notably TNFα, in epididymal, but not subcutaneous, fat depots. When NK cells were depleted either with neutralizing antibodies or genetic ablation in E4bp4(+/-) mice, obesity-induced insulin resistance improved in parallel with decreases in both adipose tissue macrophage (ATM) numbers, and ATM and adipose tissue inflammation. Conversely, expansion of NK cells following IL-15 administration or reconstitution of NK cells into E4bp4(-/-) mice increased both ATM numbers and adipose tissue inflammation and exacerbated HFD-induced insulin resistance. These results indicate that adipose NK cells control ATMs as an upstream regulator potentially by producing proinflammatory mediators, including TNFα, and thereby contribute to the development of obesity-induced insulin resistance.

  13. Alterations in skeletal muscle protein-tyrosine phosphatase activity and expression in insulin-resistant human obesity and diabetes.

    PubMed Central

    Ahmad, F; Azevedo, J L; Cortright, R; Dohm, G L; Goldstein, B J

    1997-01-01

    Obese human subjects have increased protein-tyrosine phosphatase (PTPase) activity in adipose tissue that can dephosphorylate and inactivate the insulin receptor kinase. To extend these findings to skeletal muscle, we measured PTPase activity in the skeletal muscle particulate fraction and cytosol from a series of lean controls, insulin-resistant obese (body mass index > 30) nondiabetic subjects, and obese individuals with non-insulin-dependent diabetes. PTPase activities in subcellular fractions from the nondiabetic obese subjects were increased to 140-170% of the level in lean controls (P < 0.05). In contrast, PTPase activity in both fractions from the obese subjects with non-insulin-dependent diabetes was significantly decreased to 39% of the level in controls (P < 0.05). By immunoblot analysis, leukocyte antigen related (LAR) and protein-tyrosine phosphatase 1B had the greatest increase (threefold) in the particulate fraction from obese, nondiabetic subjects, and immunodepletion of this fraction using an affinity-purified antibody directed at the cytoplasmic domain of leukocyte antigen related normalized the PTPase activity when compared to the activity from control subjects. These findings provide further support for negative regulation of insulin action by specific PTPases in the pathogenesis of insulin resistance in human obesity, while other regulatory mechanisms may be operative in the diabetic state. PMID:9218523

  14. 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.

  15. Circulating leptin and osteoprotegerin levels affect insulin resistance in healthy premenopausal obese women.

    PubMed

    Ugur-Altun, Betul; Altun, Armagan

    2007-11-01

    We investigated the relationship between circulating leptin and osteoprotegerin (OPG) levels and insulin resistance assessed by HOMA-IR in premenopausal obese and normal weight women. Thirty four obese women (age 31 +/- 8 years) (BMI 35 +/- 4 kg/m(2)) with 19 healthy controls (age 31 +/- 7 years) (BMI <25 kg/m(2)) (BMI 21 +/- 2 kg/m(2)) were included in the study. Women were healthy and had no osteoporosis. Circulating leptin levels were significantly higher in obese women (17.11 +/- 2.05 ng/mL vs. 8.38 +/- 4.71 ng/mL, p <0.0001) and decreased OPG levels were found (14.7 +/- 7.15 pg/mL vs. 19.17 +/- 6.37 pg/mL, p = 0.03). Leptin showed a positive correlation with BMI (r = 0.851, p <0.0001), waist-to-hip ratio (r = 0.692, p <0.0001), fasting insulin (r = 0.441, p <0.001), HOMA-IR (r = 0.412, p = 0.002), fibrinogen (r = 0.387, p = 0.004), uric acid (r = 0.293, p = 0.033), hematocrit (r = 0.394, p = 0.003), systolic (r = 0.504, p <0.0001), and diastolic blood pressure (r = 0.363, p = 0.008). OPG showed a negative correlation with insulin (r = -0.341, p = 0.013) and HOMA-IR (r = -0.324, p = 0.018). In obese women group, the regression equation of HOMA-IR was (HOMA-IR = [0.095 x leptin]-[0.051 x OPG] + 1.71). However, there was no relation between leptin and OPG levels. In conclusion, circulating leptin and OPG levels were related to insulin resistance in premenopausal obese women. However, leptin had no interference in OPG in premenopausal women. PMID:17923273

  16. Obesity does not aggravate osteoporosis or osteoblastic insulin resistance in orchiectomized rats.

    PubMed

    Potikanond, Saranyapin; Rattanachote, Pinyada; Pintana, Hiranya; Suntornsaratoon, Panan; Charoenphandhu, Narattaphol; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2016-02-01

    The present study aimed to test the hypothesis that testosterone deprivation impairs osteoblastic insulin signaling, decreases osteoblast survival, reduces bone density, and that obesity aggravates those deleterious effects in testosterone-deprived rats. Twenty four male Wistar rats underwent either a bilateral orchiectomy (O, n=12) or a sham operation (S, n=12). Then the rats in each group were further divided into two subgroups fed with either a normal diet (ND) or a high-fat diet (HF) for 12 weeks. At the end of the protocol, blood samples were collected to determine metabolic parameters and osteocalcin ratios. The tibiae were collected to determine bone mass using microcomputed tomography and for osteoblast isolation. The results showed that rats fed with HF (sham-operated HF-fed rats (HFS) and ORX HF-fed rats (HFO)) developed peripheral insulin resistance and had decreased trabecular bone density. In ND-fed rats, only the ORX ND-fed rats (NDO) group had decreased trabecular bone density. In addition, osteoblastic insulin resistance, as indicated by a decrease in tyrosine phosphorylation of the insulin receptor and Akt, were observed in all groups except the sham-operated ND-fed rats (NDS) rats. Those groups, again with the exception of the NDS rats, also had decreased osteoblastic survival. No differences in the levels of osteoblastic insulin resistance and osteoblastic survival were found among the NDO, HFS, and HFO groups. These findings suggest that either testosterone deprivation or obesity alone can impair osteoblastic insulin signaling and decrease osteoblastic survival leading to the development of osteoporosis. However, obesity does not aggravate those deleterious effects in the bone of testosterone-deprived rats. PMID:26675491

  17. The role of adipose cell size and adipose tissue insulin sensitivity in the carbohydrate intolerance of human obesity.

    PubMed

    Salans, L B; Knittle, J L; Hirsch, J

    1968-01-01

    Glucose metabolism and insulin sensitivity of isolated human adipose tissue was studied as a function of adipose cell size and number. Glucose metabolism by these tissues was closely related to the number of cells in the fragment, irrespective of cell size. Adipose cells of obese individuals metabolized glucose to carbon dioxide and triglyceride at rates similar to adipose cells of nonobese subjects. In contrast, insulin responsiveness of adipose tissue was dependent upon adipose cell size. The larger its adipose cells the less insulin sensitive was the tissue. Thus, adipose tissue of obese subjects, with enlarged cells, showed a diminished response to insulin. After weight loss and reduction in adipose cell size, insulin sensitivity of the adipose tissue of obese patients was restored to normal. When adipose tissue of obese individuals showed impaired responsiveness to insulin, their plasma insulin levels, after oral glucose, were elevated. Weight loss and reduction in adipose cell size restored plasma insulin concentration to normal, concomitant with the return of normal tissue insulin sensitivity.

  18. Insulin sensitivity decreases with obesity, and lean cats with low insulin sensitivity are at greatest risk of glucose intolerance with weight gain.

    PubMed

    Appleton, D J; Rand, J S; Sunvold, G D

    2001-12-01

    This study quantifies the effects of marked weight gain on glucose and insulin metabolism in 16 cats which increased their weight by an average of 44.2% over 10 months. Significantly, the development of feline obesity was accompanied by a 52% decrease in tissue sensitivity to insulin and diminished glucose effectiveness. In addition, glucose intolerance and abnormal insulin response occurred in some cats. An important finding was that normal weight cats with low insulin sensitivity and glucose effectiveness were at increased risk of developing impaired glucose tolerance with obesity. High basal insulin concentrations or low acute insulin response to glucose also independently increased the risk for developing impaired glucose tolerance. Male cats gained more weight relative to females and this, combined with their tendency to lower insulin sensitivity and higher insulin concentrations, may explain why male cats are at greater risk for diabetes. Results suggest an underlying predisposition for glucose intolerance in some cats, which is exacerbated by obesity. These cats may be more at risk of progressing to overt type 2 diabetes mellitus.

  19. 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

  20. Socio-Demographic and Dietary Factors Associated with Excess Body Weight and Abdominal Obesity among Resettled Bhutanese Refugee Women in Northeast Ohio, United States

    PubMed Central

    Bhatta, Madhav P.; Assad, Lori; Shakya, Sunita

    2014-01-01

    Studies of obesity and related health conditions among the Bhutanese, one of the largest refugee groups resettled in the United States in the past five years, are limited. This study examined the factors associated with excess body weight (body mass index ≥ 23 kg/m2) and abdominal obesity (waist circumference > 80 cm) in a community-based sample of 18–65 year old Bhutanese refugee women in Northeast Ohio. A Nepali-language questionnaire was used to measure socio-demographic and dietary factors. Height, weight, and waist circumference were measured to define excess body weight and abdominal obesity. The mean (±standard deviation) age of the 108 participants was 36.5 (±12.2) years and length of time in the U.S. was 19.4 (±11.9) months. Overall, 64.8% and 69.4% of the women had excess body weight and abdominal obesity, respectively. Age was significantly associated with both excess body weight (odds ratio: 1.10; 95% confidence interval: 1.05–1.16) and abdominal obesity (1.09; 1.04–1.14). Consuming meat (4.01; 1.14–14.60) was significantly associated with excess body weight but not abdominal obesity. These findings suggest the need for lifestyle and dietary change education programs among this new and vulnerable group to reduce the prevalence of excess body weight and abdominal obesity and their health consequences. PMID:24968209

  1. Joint association of nicotinic acetylcholine receptor variants with abdominal obesity in American Indians: the Strong Heart Family Study.

    PubMed

    Zhu, Yun; Yang, Jingyun; Yeh, Fawn; Cole, Shelley A; Haack, Karin; Lee, Elisa T; Howard, Barbara V; Zhao, Jinying

    2014-01-01

    Cigarette smoke is a strong risk factor for obesity and cardiovascular disease. The effect of genetic variants involved in nicotine metabolism on obesity or body composition has not been well studied. Though many genetic variants have previously been associated with adiposity or body fat distribution, a single variant usually confers a minimal individual risk. The goal of this study is to evaluate the joint association of multiple variants involved in cigarette smoke or nicotine dependence with obesity-related phenotypes in American Indians. To achieve this goal, we genotyped 61 tagSNPs in seven genes encoding nicotine acetylcholine receptors (nAChRs) in 3,665 American Indians participating in the Strong Heart Family Study. Single SNP association with obesity-related traits was tested using family-based association, adjusting for traditional risk factors including smoking. Joint association of all SNPs in the seven nAChRs genes were examined by gene-family analysis based on weighted truncated product method (TPM). Multiple testing was controlled by false discovery rate (FDR). Results demonstrate that multiple SNPs showed weak individual association with one or more measures of obesity, but none survived correction for multiple testing. However, gene-family analysis revealed significant associations with waist circumference (p = 0.0001) and waist-to-hip ratio (p = 0.0001), but not body mass index (p = 0.20) and percent body fat (p = 0.29), indicating that genetic variants are jointly associated with abdominal, but not general, obesity among American Indians. The observed combined genetic effect is independent of cigarette smoking per se. In conclusion, multiple variants in the nAChR gene family are jointly associated with abdominal obesity in American Indians, independent of general obesity and cigarette smoking per se.

  2. Skeletal muscle salt inducible kinase 1 promotes insulin resistance in obesity

    PubMed Central

    Nixon, Mark; Stewart-Fitzgibbon, Randi; Fu, Jingqi; Akhmedov, Dmitry; Rajendran, Kavitha; Mendoza-Rodriguez, Maria G.; Rivera-Molina, Yisel A.; Gibson, Micah; Berglund, Eric D.; Justice, Nicholas J.; Berdeaux, Rebecca

    2015-01-01

    Objective Insulin resistance causes type 2 diabetes mellitus and hyperglycemia due to excessive hepatic glucose production and inadequate peripheral glucose uptake. Our objectives were to test the hypothesis that the proposed CREB/CRTC2 inhibitor salt inducible kinase 1 (SIK1) contributes to whole body glucose homeostasis in vivo by regulating hepatic transcription of gluconeogenic genes and also to identify novel SIK1 actions on glucose metabolism. Methods We created conditional (floxed) SIK1-knockout mice and studied glucose metabolism in animals with global, liver, adipose or skeletal muscle Sik1 deletion. We examined cAMP-dependent regulation of SIK1 and the consequences of SIK1 depletion on primary mouse hepatocytes. We probed metabolic phenotypes in tissue-specific SIK1 knockout mice fed high fat diet through hyperinsulinemic-euglycemic clamps and biochemical analysis of insulin signaling. Results SIK1 knockout mice are viable and largely normoglycemic on chow diet. On high fat diet, global SIK1 knockout animals are strikingly protected from glucose intolerance, with both increased plasma insulin and enhanced peripheral insulin sensitivity. Surprisingly, liver SIK1 is not required for regulation of CRTC2 and gluconeogenesis, despite contributions of SIK1 to hepatocyte CRTC2 and gluconeogenesis regulation ex vivo. Sik1 mRNA accumulates in skeletal muscle of obese high fat diet-fed mice, and knockout of SIK1 in skeletal muscle, but not liver or adipose tissue, improves insulin sensitivity and muscle glucose uptake on high fat diet. Conclusions SIK1 is dispensable for glycemic control on chow diet. SIK1 promotes insulin resistance on high fat diet by a cell-autonomous mechanism in skeletal muscle. Our study establishes SIK1 as a promising therapeutic target to improve skeletal muscle insulin sensitivity in obese individuals without deleterious effects on hepatic glucose production. PMID:26844205

  3. 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

  4. Overweight and General and Abdominal Obesity in a Representative Sample of Spanish Adults: Findings from the ANIBES Study.

    PubMed

    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/m(2), WHtR < 0.5), whereas 50.1% had weight excess and high WHtR (BMI ≥ 25 kg/m(2), 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.

  5. Overweight and General and Abdominal Obesity in a Representative Sample of Spanish Adults: Findings from the ANIBES Study.

    PubMed

    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/m(2), WHtR < 0.5), whereas 50.1% had weight excess and high WHtR (BMI ≥ 25 kg/m(2), 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

  6. Body composition and -174G/C interleukin-6 promoter gene polymorphism: association with progression of insulin resistance in normal weight obese syndrome.

    PubMed

    Di Renzo, L; Bertoli, A; Bigioni, M; Del Gobbo, V; Premrov, M G; Calabrese, V; Di Daniele, N; De Lorenzo, A

    2008-01-01

    Insulin resistance and obesity are intimately related to a chronic low grade systemic inflammation. Interleukin-6 (IL-6) may influence the pathogenesis of obesity-related diseases. The aim of this study is to investigate the effect of body's fat mass on the relationships between -174G/C IL-6 promoter gene polymorphism, IL-6 circulating level and insulin resistance. A population of 150 Caucasian women was studied, subdivided according to their body composition in non-obese (NW), Normal Weight Obese (NWO) and preobese-obese (OB). The NWO subjects were found in an intermediate position between the NW and OB subjects in terms of body weight, fat mass percentage (FM%), abdominal FAT%, hs-CRP and plasma triglyceride level. Fasting plasma IL-6 concentration was positively correlated with the homeostasis model assessment for insulin resistance (HOMA-IR) in all subjects analyzed (P=0.0014). In NWO and OB women a significantly increased IL-6 mean value was observed compared with NW subjects. In G/G population, the IL-6 plasma level of NWO and OB was significantly higher with respect to NW. No significant differences of IL-6 concentrations were observed in the three groups carrying G/C genotype. NWO and OB women homozygous for the allele C have significantly lower value of IL-6 with respect to NW subjects. IL-6 concentration was positively correlated with FM% in G/G (R(2)=0.397, P<0.001) and was negatively correlated in C/C (R(2)=0.459, P=0.002). No significant correlation was observed in G/C genotype (R(2)=0.041, P=0.173). In conclusion our study confirms that, at least in Italian Caucasian females, the FM% is a major determinant of an increase in IL-6 production and insulin resistance. -174 G/C IL-6 promoter polymorphism represents a marker which could help to identify, time in advance, "vulnerable" individuals at risk of age and obesity related diseases.

  7. [EXPRESSION OF GENES, WHICH CONTROL GLUCOSE METABOLISM, IN BLOOD CELLS OF THE OBESE BOYS WITH INSULIN RESISTANCE].

    PubMed

    Tiazhka, O V; Minchenko, D O; Davydov, V V; Moliavko, O S; Budreiko, O A; Kulieshova, D K; Minchenko, O H

    2015-01-01

    We studied the expression of genes, which responsible for glucose metabolism, in the blood of obese boys with and without of insulin resistance as well as in normal (control) individuals. It was shown that the expression level of PFKFB3 gene is increased, PFKFB1 and INSIG2--is decreased, but HK2 gene--significantly does not change in the blood cells of obese boys with normal insulin sensitivity as compared to control group. Insulin resistance in obese boys leads to up-regulation of INSIG2 gene expression as well as to down-regulation of PFKFB1, PFKFB3, and HK2 genes in the blood.cells as compared to obese patients with normal insulin sensitivity. Results of this study provide evidence that obesity affects the expression of the subset of glucose metabolism-related genes in the blood cells and that insulin resistance in obesity is associated with changes in the expression level of PFKFB1, PFKFB3, HK2, and INSIG2 genes, which contribute to the development of insulin resistance as well as glucose intolerance. PMID:26827442

  8. Roles of obese-insulin resistance and anti-diabetic drugs on the heart with ischemia-reperfusion injury.

    PubMed

    Apaijai, Nattayaporn; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2014-12-01

    The incidence of obesity with insulin resistance is increasing worldwide. This condition is also known as a risk factor of coronary artery disease and associated with increased arrhythmias, impaired left ventricular function, and increased infarct size during cardiac ischemia-reperfusion (I/R) injury. The proposed mechanisms are due to impaired glucose utilization and pro-survival signaling molecules, and increased inflammatory cytokines, which have been demonstrated in the I/R hearts in various models of obese-insulin resistance. However, the cardiac effects of diets in the I/R heart are still unsettled since several studies reported that high-caloric diet consumption might protect the heart from I/R injury. Although several therapeutic strategies such as anti-diabetic drugs, natural compounds as well as treadmill exercise have been proposed to exert cardioprotection in the I/R heart in obese-insulin resistant animals, some interventions including ischemic post-conditioning failed to protect the heart from I/R injury. In this comprehensive review, reports from both genetic deletion and dietary-induced obese-insulin resistant animal models regarding the effects of obese-insulin resistance on metabolic parameters, cardiac function, infarct size, and molecular mechanisms under I/R injury are summarized. Moreover, the effects of anti-diabetic drugs and other pharmacological interventions on these parameters in an obese-insulin resistant model under I/R injury are also comprehensively summarized and discussed.

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

    PubMed Central

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

    2014-01-01

    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/m2), 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 R2 = 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. PMID:25056918

  10. SIRT3 Deficiency Induces Endothelial Insulin Resistance and Blunts Endothelial-Dependent Vasorelaxation in Mice and Human with Obesity

    PubMed Central

    Yang, Lu; Zhang, Julei; Xing, Wenjuan; Zhang, Xing; Xu, Jie; Zhang, Haifeng; Chen, Li; Ning, Xiaona; Ji, Gang; Li, Jia; Zhao, Qingchuan; Gao, Feng

    2016-01-01

    Recent evidence implicates the critical role of Sirtuin 3 (SIRT3) in the development of many metabolic diseases, but the contribution of SIRT3 to vascular homeostasis remains largely unknown. The aim of this study was to investigate the role of SIRT3 in endothelial insulin resistance and vascular dysfunction in obesity. We found an impaired insulin-induced mesenteric vasorelaxation and concomitant reduced vascular SIRT3 expression in morbid obese human subjects compared with the non-obese subjects. Downregulation of SIRT3 in cultured human endothelial cells increased mitochondrial reactive oxygen species (mtROS) and impaired insulin signaling as evidenced by decreased phosphorylation of Akt and endothelial nitric oxide synthase and subsequent reduced nitric oxide (NO) release. In addition, obese mice induced by 24-week high-fat diet (HFD) displayed an impaired endothelium-dependent vasorelaxation to both insulin and acetylcholine, which was further exacerbated by the gene deletion of Sirt3. Scavenging of mtROS not only restored insulin-stimulated NO production in SIRT3 knockdown cells, but also improved insulin-induced vasorelaxation in SIRT3 knockout mice fed with HFD. Taken together, our findings suggest that SIRT3 positively regulates endothelial insulin sensitivity and show that SIRT3 deficiency and resultant increased mtROS contribute to vascular dysfunction in obesity. PMID:27000941

  11. Association of Rotating Night Shift Work with BMI and Abdominal Obesity among Nurses and Midwives

    PubMed Central

    Peplonska, Beata; Bukowska, Agnieszka; Sobala, Wojciech

    2015-01-01

    Background Mounting epidemiological evidence suggests that night shift work may contribute to the etiology of increased body weight. The present study aimed to examine association between rotating night shift work and body mass index (BMI), and abdominal adiposity respectively among nurses and midwives. Methods A cross-sectional study was conducted among 724 female nurses and midwives, aged 40-60 years (354 rotating night shift and 370 daytime workers) in Łódź, Poland, between 2008 and 2011. Information about occupational history and potential confounders was collected during personal interviews. Anthropometric measurements of body weight, height, waist (WC) and hip (HC) circumference were made, and body mass index (BMI), waist to hip ratio (WHR) and waist to height ratio (WHtR) were calculated. GLM regression models and multinomial logit regression models were fitted to explore the association between night shift work and anthropometric parameters, with adjustment for age, body silhouette at age 20, current smoking status, packyears, marital status, and menopausal hormone therapy use. Results Cumulative night shift work showed significant associations with BMI, WC, HC and WHtR, with BMI increasing by 0.477 kg/m2 per 1000 night duties and by 0.432 kg/m2 per 10000 night shift hours, WC increasing respectively by 1.089 cm and 0.99 cm, and HC by 0.72 cm and WHtR by 0.007 cm for both metrics. Both current and cumulative night work was associated with obesity (BMI≥30kg/m2), with OR=3.9 (95%CI:1.5-9.9), in women reporting eight or more night shifts per month. Conclusion The results of the study support the previously reported relations between night shift work and development of obesity. PMID:26196859

  12. Effect of obesity and type 2 diabetes on protein anabolic response to insulin in elderly women.

    PubMed

    Murphy, Jessica; Chevalier, Stéphanie; Gougeon, Réjeanne; Goulet, Éric D B; Morais, José A

    2015-09-01

    Obesity and type 2 diabetes have been shown to alter the insulin sensitivity of glucose and protein metabolism in middle-aged women. We aimed to determine whether these findings translate to the elderly who are at increased risk of muscle loss. We assessed whole-body protein (1-(13)C-leucine) and glucose (3-(3)H-glucose) kinetics in 10 healthy (age: 71.6±1.8years; BMI: 23.2±0.8kg/m(2)), 8 obese (age: 72.9±1.3; BMI: 33.1±1.0) and 8 obese well-controlled type 2 diabetic (age: 69.8±1.6; BMI: 34.4±1.5) elderly women in the postabsorptive state and during a hyperinsulinemic, euglycemic, isoaminoacidemic clamp. All subjects followed an isoenergetic, protein-controlled diet for 6days preceding the clamp. The net protein anabolic response to hyperinsulinemia was similarly blunted in obese (0.08±0.06) and obese type 2 diabetic women (0.06±0.04) compared to healthy women (0.24±0.05μmol·kg fat free mass(-1)·min(-1); ANOVA p=0.018). In contrast, the insulin-mediated glucose disposal (healthy: 9.72±0.67) was decreased with obesity (6.96±0.86) and further with diabetes (5.23±0.27mg·kg fat free mass(-1)·min(-1); ANOVA p<0.001). Endogenous glucose production was not completely suppressed during the clamp only in diabetic women. Thus, the glucose infusion rate was the lowest in this group. Obese elderly women with and without type 2 diabetes have a similar degree of insulin resistance of protein anabolism, despite worse glucose metabolism in type 2 diabetes. Similar to previous findings in middle-aged women, obesity exerted a blunting effect on protein anabolism, which may contribute to the development of sarcopenic obesity. Our results suggest that the presence of type 2 diabetes at an advancing age does not further aggravate this effect. PMID:26068615

  13. Association Between Thyrotropin Levels and Insulin Sensitivity in Euthyroid Obese Adolescents

    PubMed Central

    Javed, Asma; Balagopal, P. Babu; Vella, Adrian; Fischer, Philip R.; Piccinini, Francesca; Dalla Man, Chiara; Cobelli, Claudio; Giesler, Paula D.; Laugen, Jeanette M.

    2015-01-01

    Background: Thyrotropin (TSH) levels display a positive association with body mass index (BMI), and the prevalence of isolated hyperthyrotropinemia is higher in obese adolescents compared to their normal weight controls. However, the metabolic significance of the higher TSH in obese adolescents is less clear. The objective of this study was to determine the relationship between TSH concentrations and insulin sensitivity, lipids, and adipokines in euthyroid, non-diabetic, obese adolescents. Methods: Thirty-six euthyroid, non-diabetic, obese adolescents between the ages of 12 and 18 years underwent a 75 g oral glucose tolerance test. Insulin sensitivity (Si) and pancreatic β-cell function as assessed by disposition index (DI) were measured using the oral glucose minimal model approach. Cholesterol (total, low-density lipoprotein [LDL-C], and high-density lipoprotein [HDL-C]), triglycerides (TG), interleukin-6 (IL-6), total and high molecular weight (HMW) adiponectin, and retinol binding protein-4 (RBP4) were also determined. Associations between measures of thyroid function and Si, DI, lipids, and adipokines were computed using Pearson's correlation coefficient and multiple regression analysis. Results: The mean age of the subjects was 14.3±1.88 years, and the mean BMI was 32.5±4.65 kg/m2; 97% were non-Hispanic white and 47% were male. The mean TSH was 2.7±1.2 mIU/L. Increasing serum TSH was correlated with decreasing Si (log Si) in the entire cohort (p=0.03), but this relationship persisted only in males (p=0.02). The correlation between TSH and Si in males remained significant after adjusting for BMI (p=0.02). There was no correlation between TSH and pancreatic β-cell function as assessed by DI (p=0.48). TSH correlated positively with LDL-C (p=0.04) and IL-6 (p=0.03), but these associations vanished or weakened after adjusting for BMI (LDL-C p-value=0.44; IL-6 p-value=0.07). Conclusions: This study suggests a sex-specific association between TSH and insulin

  14. 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

  15. 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

  16. Adipose tissue natriuretic peptide receptor expression is related to insulin sensitivity in obesity and diabetes

    PubMed Central

    Kovacova, Zuzana; Tharp, William G.; Liu, Dianxin; Wei, Wan; Xie, Hui

    2016-01-01

    Objective Cardiac natriuretic peptides (NPs) bind to two receptors (NPRA‐mediator of signaling; NPRC‐clearance receptor) whose ratio, NPRR (NPRA/NPRC), determines the NP bioactivity. This study investigated the relationship of NP receptor gene expression in adipose tissue and muscle with obesity and glucose intolerance. Prospectively, the study also assessed whether changes in NP receptor expression and thermogenic gene markers accompanied improvements of insulin sensitivity. Methods A cross‐sectional study of subjects with a wide range of BMI and glucose tolerance (n = 50) was conducted, as well as a randomized 12‐week trial of subjects with type 2 diabetes mellitus (T2DM) treated with pioglitazone (n = 9) or placebo (n = 10). Results NPRR mRNA was significantly lower in adipose tissue of subjects with obesity when compared with lean subjects (P ≤ 0.001). NPRR decreased with progression from normal glucose tolerance to T2DM (P < 0.01) independently of obesity. Treatment of subjects with T2DM with pioglitazone increased NPRR in adipose tissue (P ≤ 0.01) in conjunction with improvements in insulin sensitivity and increases of the thermogenic markers PPARγ coactivator‐1α and uncoupling protein 1 (P ≤ 0.01). Conclusions Decreased adipose tissue NPRR was associated with obesity, glucose intolerance, and insulin resistance. This relationship was not observed for skeletal muscle NPRR. Pharmacological improvement of insulin sensitivity in subjects with T2DM was tied to improvement in NPRR and increased expression of genes involved in thermogenic processes. PMID:26887289

  17. 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

  18. Added impact of obesity and insulin resistance in nocturnal blood pressure elevation in children and adolescents.

    PubMed

    Lurbe, Empar; Torro, Isabel; Aguilar, Francisco; Alvarez, Julio; Alcon, Jose; Pascual, Jose Maria; Redon, Josep

    2008-03-01

    The aim of the present study was to analyze the relationship between insulin resistance and the ambulatory blood pressure components in obese children and adolescents. Eighty-seven overweight and obese white children and adolescents of both sexes, of European origin from 6 to 18 years of age (mean age: 10.9+/-2.7 years), were selected. Obesity was defined on the basis of a threshold body mass index z score >2 (Cole's least mean square method) and overweight with a body mass index from the 85th to 97th percentile. A validated oscillometric method was used to measure ambulatory BP (Spacelabs 90207) during 24 hours. Fasting glucose and insulin were measured, and the homeostasis model assessment index was calculated. Subjects were grouped into tertiles of homeostasis model assessment index. No significant differences in terms of age, sex, and body mass index z score distribution were observed among groups. When adjusted by age, sex, and height, nocturnal systolic blood pressure and heart rate were significantly higher in subjects in the highest homeostasis model assessment index tertile (>4.7) as compared with those of the other groups, whereas no differences were observed for awake systolic blood pressure or heart rate. Whereas body mass index z score was more closely related with blood pressure and heart rate values, waist circumference was strongly related with insulin resistance. Moreover, both waist circumference and insulin resistance were mainly associated with higher nocturnal but not with awake blood pressure. The early increment of nocturnal blood pressure and heart rate associated with hyperinsulinemia may be a harbinger of hypertension-related insulin resistance and may contribute to heightened cardiovascular risk associated with this condition. PMID:18195166

  19. Association of insulin sensitivity and muscle strength in overweight and obese sedentary postmenopausal women.

    PubMed

    Karelis, Antony D; Tousignant, Benoit; Nantel, Julie; Proteau-Labelle, Majorique; Malita, Florin M; St-Pierre, David H; Brochu, Martin; Doucet, Eric; Rabasa-Lhoret, Rémi

    2007-04-01

    The objective of this study was to examine the relationship between insulin sensitivity and lower body muscle strength in overweight and obese sedentary postmenopausal women. The design of the study was cross-sectional. The study population consisted of 82 non-diabetic overweight and obese sedentary postmenopausal women (age: 58.2 +/- 5.1 y; body mass index (BMI): 32.4 +/- 4.6 kg.m-2). Subjects were classified by dividing the entire cohort into quartiles based on relative insulin sensitivity expressed per kilograms of lean body mass (LBM) (Q1, < 10.3, vs. Q2, 10.3-12.4, vs. Q3, 12.5-14.0, vs. Q4, >14.0 mg.min-1.kg LBM-1). We measured insulin sensitivity (using the hyperinsulinemic-euglycemic clamp technique), body composition (using dual-energy X-ray absorptiometry), visceral fat and muscle attenuation (using computed tomography), and a lower-body muscle strength index expressed as weight lifted in kilograms per kilogram of LBM (kg.kg LBM-1) (using weight-training equipment). A positive and significant relationship was observed between insulin sensitivity and the muscle strength index (r = 0.37; p < 0.001). Moreover, a moderate but significant correlation was observed between the muscle strength index and muscle attenuation (r = 0.22; p < 0.05). Finally, the muscle strength index was significantly higher in the Q4 group compared with the Q2 and Q1 groups, respectively (3.78 +/- 1.13 vs. 2.99 +/- 0.77 and 2.93 +/- 0.91 kg.kg LBM-1; p < 0.05). Insulin sensitivity is positively associated with lower-body muscle strength in overweight and obese sedentary postmenopausal women.

  20. 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.

  1. 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

  2. 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. PMID:27175804

  3. Chronic reduction of GIP secretion alleviates obesity and insulin resistance under high-fat diet conditions.

    PubMed

    Nasteska, Daniela; Harada, Norio; Suzuki, Kazuyo; Yamane, Shunsuke; Hamasaki, Akihiro; Joo, Erina; Iwasaki, Kanako; Shibue, Kimitaka; Harada, Takanari; Inagaki, Nobuya

    2014-07-01

    Gastric inhibitory polypeptide (GIP) exhibits potent insulinotropic effects on β-cells and anabolic effects on bone formation and fat accumulation. We explored the impact of reduced GIP levels in vivo on glucose homeostasis, bone formation, and fat accumulation in a novel GIP-GFP knock-in (KI) mouse. We generated GIP-GFP KI mice with a truncated prepro-GIP gene. The phenotype was assessed in heterozygous and homozygous states in mice on a control fat diet and a high-fat diet (HFD) in vivo and in vitro. Heterozygous GIP-GFP KI mice (GIP-reduced mice [GIP(gfp/+)]) exhibited reduced GIP secretion; in the homozygous state (GIP-lacking mice [GIP(gfp/gfp)]), GIP secretion was undetectable. When fed standard chow, GIP(gfp/+) and GIP(gfp/gfp) mice showed mild glucose intolerance with decreased insulin levels; bone volume was decreased in GIP(gfp/gfp) mice and preserved in GIP(gfp/+) mice. Under an HFD, glucose levels during an oral glucose tolerance test were similar in wild-type, GIP(gfp/+), and GIP(gfp/gfp) mice, while insulin secretion remained lower. GIP(gfp/+) and GIP(gfp/gfp) mice showed reduced obesity and reduced insulin resistance, accompanied by higher fat oxidation and energy expenditure. GIP-reduced mice demonstrate that partial reduction of GIP does not extensively alter glucose tolerance, but it alleviates obesity and lessens the degree of insulin resistance under HFD conditions, suggesting a potential therapeutic value.

  4. 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 ...

  5. 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.

  6. 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

  7. Obesity, insulin resistance, adipocytokines and breast cancer: New biomarkers and attractive therapeutic targets.

    PubMed

    Dalamaga, Maria

    2013-08-20

    Worldwide, breast cancer (BC) represents the most common type of non-skin human malignancy and the second leading cause of cancer-related deaths amid women in Western countries. Obesity and its metabolic complications have rapidly become major global health issues and are associated with increased risk for cancer, especially BC in postmenopausal women. Adipose tissue is considered as a genuine endocrine organ secreting a variety of bioactive adipokines, such as leptin, adiponectin, resistin and nicotinamide phosphoribosyl-transferase/visfatin. Recent evidence has indicated that the constellation of obesity, insulin resistance and adipokines is associated with the risk and prognosis of postmenopausal BC. Direct evidence is growing rapidly supporting the stimulating and/or inhibiting role of adipokines in the process of development and progression of BC. Adipokines could exert their effects on the normal and neoplastic mammary tissue by endocrine, paracrine and autocrine mechanisms. Recent studies support a role of adipokines as novel risk factors and potential diagnostic and prognostic biomarkers in BC. This editorial aims at providing important insights into the potential pathophysiological mechanisms linking adipokines to the etiopathogenesis of BC in the context of a dysfunctional adipose tissue and insulin resistance in obesity. A better understanding of these mechanisms may be important for the development of attractive preventive and therapeutic strategies against obesity-related breast malignancy. PMID:24520544

  8. Islet adaptation to obesity and insulin resistance in WNIN/GR-Ob rats

    PubMed Central

    Singh, Himadri; Ganneru, Sireesha; Malakapalli, Venkata; Chalasani, Maniprabha; Nappanveettil, Giridharan; Bhonde, Ramesh R; Venkatesan, Vijayalakshmi

    2014-01-01

    WNIN/GR-Ob mutant rat is a novel animal model to study metabolic syndrome (obesity, insulin resistance, hyperinsulinemia, impaired glucose tolerance and cardiovascular diseases). We have investigated the islet characteristics of obese mutants at different age groups (1, 6 and 12 months) to assess the islet changes in response to early and chronic metabolic stress. Our data demonstrates altered islet cell morphology and function (hypertrophy, fibrotic lesions, vacuolation, decreased stimulation index, increased TNFα, ROS and TBARS levels) in mutants as compared to controls. Furthermore, network analysis (gene-gene interaction) studied in pancreas demonstrated increased inflammation as a key factor underlying obesity/metabolic syndrome in mutants. These observations pave way to explore this model to understand islet adaptation in response to metabolic syndrome. PMID:25833252

  9. Evaluation of Nerve Conduction Studies in Obese Children With Insulin Resistance or Impaired Glucose Tolerance.

    PubMed

    Ince, Hülya; Taşdemir, Haydar Ali; Aydin, Murat; Ozyürek, Hamit; Tilki, Hacer Erdem

    2015-07-01

    The aim of the study was to investigate nerve conduction studies in terms of neuropathic characteristics in obese patients who were in prediabetes stage and also to determine the abnormal findings. The study included 69 obese adolescent patients between April 2009 and December 2010. All patients and control group underwent motor (median, ulnar, tibial, and peroneal) and sensory (median, ulnar, sural, and medial plantar) nerve conduction studies and sympathetic skin response test. Sensory response amplitude of the medial plantar nerve was significantly lower in the patients with impaired glucose tolerance and insulin resistance. To our knowledge, the present study is the first study demonstrating the development of sensory and autonomic neuropathy due to metabolic complications of obesity in adolescent children even in the period without development of diabetes mellitus. We recommend that routine electrophysiological examinations be performed, using medial plantar nerve conduction studies and sympathetic skin response test. PMID:25342307

  10. Evaluation of Nerve Conduction Studies in Obese Children With Insulin Resistance or Impaired Glucose Tolerance.

    PubMed

    Ince, Hülya; Taşdemir, Haydar Ali; Aydin, Murat; Ozyürek, Hamit; Tilki, Hacer Erdem

    2015-07-01

    The aim of the study was to investigate nerve conduction studies in terms of neuropathic characteristics in obese patients who were in prediabetes stage and also to determine the abnormal findings. The study included 69 obese adolescent patients between April 2009 and December 2010. All patients and control group underwent motor (median, ulnar, tibial, and peroneal) and sensory (median, ulnar, sural, and medial plantar) nerve conduction studies and sympathetic skin response test. Sensory response amplitude of the medial plantar nerve was significantly lower in the patients with impaired glucose tolerance and insulin resistance. To our knowledge, the present study is the first study demonstrating the development of sensory and autonomic neuropathy due to metabolic complications of obesity in adolescent children even in the period without development of diabetes mellitus. We recommend that routine electrophysiological examinations be performed, using medial plantar nerve conduction studies and sympathetic skin response test.

  11. Inflammatory mediators and insulin resistance in obesity: role of nuclear receptor signaling in macrophages.

    PubMed

    Fuentes, Lucía; Roszer, Tamás; Ricote, Mercedes

    2010-01-01

    Visceral obesity is coupled to a general low-grade chronic inflammatory state characterized by macrophage activation and inflammatory cytokine production, leading to insulin resistance (IR). The balance between proinflammatory M1 and antiinflammatory M2 macrophage phenotypes within visceral adipose tissue appears to be crucially involved in the development of obesity-associated IR and consequent metabolic abnormalities. The ligand-dependent transcription factors peroxisome proliferator activated receptors (PPARs) have recently been implicated in the determination of the M1/M2 phenotype. Liver X receptors (LXRs), which form another subgroup of the nuclear receptor superfamily, are also important regulators of proinflammatory cytokine production in macrophages. Disregulation of macrophage-mediated inflammation by PPARs and LXRs therefore underlies the development of IR. This review summarizes the role of PPAR and LXR signaling in macrophages and current knowledge about the impact of these actions in the manifestation of IR and obesity comorbidities such as liver steatosis and diabetic osteopenia.

  12. Islet adaptation to obesity and insulin resistance in WNIN/GR-Ob rats.

    PubMed

    Singh, Himadri; Ganneru, Sireesha; Malakapalli, Venkata; Chalasani, Maniprabha; Nappanveettil, Giridharan; Bhonde, Ramesh R; Venkatesan, Vijayalakshmi

    2014-01-01

    WNIN/GR-Ob mutant rat is a novel animal model to study metabolic syndrome (obesity, insulin resistance, hyperinsulinemia, impaired glucose tolerance and cardiovascular diseases). We have investigated the islet characteristics of obese mutants at different age groups (1, 6 and 12 months) to assess the islet changes in response to early and chronic metabolic stress. Our data demonstrates altered islet cell morphology and function (hypertrophy, fibrotic lesions, vacuolation, decreased stimulation index, increased TNFα, ROS and TBARS levels) in mutants as compared to controls. Furthermore, network analysis (gene-gene interaction) studied in pancreas demonstrated increased inflammation as a key factor underlying obesity/metabolic syndrome in mutants. These observations pave way to explore this model to understand islet adaptation in response to metabolic syndrome.

  13. Insulin resistance as a predictor of gains in body fat, weight, and abdominal fat in nondiabetic women: a prospective study.

    PubMed

    Tucker, Larry A; Tucker, Jared M

    2012-07-01

    The purpose was to determine the relationship between insulin resistance (IR) and risk of gaining body fat percentage (BF%), body weight, and abdominal fat over 18 months. A prospective cohort study was conducted using a sample of 226 women. IR was assessed using fasting blood insulin and glucose levels to calculate homeostatic model assessment (HOMA). Participants were divided into High (4th quartile) Moderate (2nd and 3rd quartiles), and Low (1st quartile) HOMA categories. BF% was estimated using plethysmography (Bod Pod), weight was measured in a standard swimsuit, and abdominal fat was indexed using the average of two circumferences taken at the umbilicus. Participants wore accelerometers and completed weighed food logs for 7 consecutive days to control for the effect of physical activity (PA) and energy intake, respectively. On average, women in the High HOMA group decreased in BF% (-0.48 ± 3.60), whereas those in the Moderate (0.40 ± 3.66) and Low HOMA (1.17 ± 3.15) groups gained BF% (F = 5.4, P = 0.0211). Changes in body weight showed a similar dose-response relationship (F = 4.7, P = 0.0317). However, baseline IR was not predictive of changes in abdominal fat (F = 0.8, P = 0.3635). Controlling for several covariates had little effect on gains in BF% and weight, but adjusting for initial BF% and/or initial weight nullified changes in BF% and weight across the IR groups. In conclusion, women with High HOMA tend to gain significantly less BF% and weight than women with low or moderate HOMA. The decreased risk appears unrelated to several covariates, except initial BF% and weight levels, which seem to play key roles in the relationships.

  14. 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

  15. Red Blood Cells from Individuals with Abdominal Obesity or Metabolic Abnormalities Exhibit Less Deformability upon Entering a Constriction

    PubMed Central

    Zeng, Nancy F.; Mancuso, Jordan E.; Zivkovic, Angela M.; Smilowitz, Jennifer T.; Ristenpart, William D.

    2016-01-01

    Abdominal obesity and metabolic syndrome (MS) are multifactorial conditions associated with increased risk of cardiovascular disease and type II diabetes mellitus. Previous work has demonstrated that the hemorheological profile is altered in patients with abdominal obesity and MS, as evidenced for example by increased whole blood viscosity. To date, however, no studies have examined red blood cell (RBC) deformability of blood from individuals with obesity or metabolic abnormalities under typical physiological flow conditions. In this study, we pumped RBCs through a constriction in a microfluidic device and used high speed video to visualize and track the mechanical behavior of ~8,000 RBCs obtained from either healthy individuals (n = 5) or obese participants with metabolic abnormalities (OMA) (n = 4). We demonstrate that the OMA+ cells stretched on average about 25% less than the healthy controls. Furthermore, we examined the effects of ingesting a high-fat meal on RBC mechanical dynamics, and found that the postprandial period has only a weak effect on the stretching dynamics exhibited by OMA+ cells. The results suggest that chronic rigidification of RBCs plays a key role in the increased blood pressure and increased whole blood viscosity observed in OMA individuals and was independent of an acute response triggered by consumption of a high-fat meal. Trial Registration ClinicalTrials.gov NCT01803633 PMID:27258098

  16. 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). PMID:23727643

  17. Insulin-regulated aminopeptidase in adipocyte is Cys-specific and affected by obesity.

    PubMed

    Alponti, Rafaela Fadoni; Viana, Luciana Godoy; Yamanouye, Norma; Silveira, Paulo Flavio

    2015-08-01

    Insulin-regulated aminopeptidase (IRAP, EC 3.4.11.3) in adipocytes is well known to traffic between high (HDM) and low (LDM) density microsomal fractions toward the plasma membrane (MF) under stimulation by insulin. However, its catalytic preference for aminoacyl substrates with N-terminal Leu or Cys is controversial. Furthermore, possible changes in its traffic under metabolic challenges are unknown. The present study investigated the catalytic activity attributable to EC 3.4.11.3 in HDM, LDM and MF from isolated adipocytes of healthy (C), food deprived (FD) and monosodium glutamate (MSG) obese rats on aminoacyl substrates with N-terminal Cys or Leu, in absence or presence of insulin. Efficacy and reproducibility of subcellular adipocyte fractionation procedure were demonstrated. Comparison among HDM vs LDM vs MF intragroup revealed that hydrolytic activity trafficking from LDM to MF under influence of insulin in C, MSG and FD is only on N-terminal Cys. In MSG the same pattern of anterograde traffic and aminoacyl preference occurred independently of insulin stimulation. The pathophysiological significance of IRAP in adipocytes seems to be linked to comprehensive energy metabolism related roles of endogenous substrates with N-terminal cysteine pair such as vasopressin and oxytocin.

  18. Obese gene expression: reduction by fasting and stimulation by insulin and glucose in lean mice, and persistent elevation in acquired (diet-induced) and genetic (yellow agouti) obesity.

    PubMed Central

    Mizuno, T M; Bergen, H; Funabashi, T; Kleopoulos, S P; Zhong, Y G; Bauman, W A; Mobbs, C V

    1996-01-01

    Mutations in the obese (ob) gene lead to obesity. This gene has been recently cloned, but the factors regulating its expression have not been elucidated. To address the regulation of the ob gene with regard to body weight and nutritional factors, Northern blot analysis was used to assess ob mRNA in adipose tissue from mice [lean, obese due to diet, or genetically (yellow agouti) obese] under different nutritional conditions. ob mRNA was elevated in both forms of obesity, compared to lean controls, correlated with elevations in plasma insulin and body weight, but not plasma glucose. In lean C57BL/6J mice, but not in mice with diet-induced obesity, ob mRNA decreased after a 48-hr fast. Similarly, in lean C57BL/6J controls, but not in obese yellow mice, i.p. glucose injection significantly increased ob mRNA. For up to 30 min after glucose injection, ob mRNA in lean mice significantly correlated with plasma glucose, but not with plasma insulin. In a separate study with only lean mice, ob mRNA was inhibited >90% by fasting, and elevated approximately 2-fold 30 min after i.p. injection of either glucose or insulin. These results suggest that in lean animals glucose and insulin enhance ob gene expression. In contrast to our results in lean mice, in obese animals ob mRNA is elevated and relatively insensitive to nutritional state, possibly due to chronic exposure to elevated plasma insulin and/or glucose. Images Fig. 1 Fig. 4 PMID:8622953

  19. Topiramate treatment improves hypothalamic insulin and leptin signaling and action and reduces obesity in mice.

    PubMed

    Caricilli, Andrea M; Penteado, Erica; de Abreu, Lélia L; Quaresma, Paula G F; Santos, Andressa C; Guadagnini, Dioze; Razolli, Daniella; Mittestainer, Francine C; Carvalheira, Jose B; Velloso, Licio A; Saad, Mario J A; Prada, Patricia O

    2012-09-01

    Topiramate (TPM) treatment has been shown to reduce adiposity in humans and rodents. The reduction in adiposity is related to decreased food intake and increased energy expenditure. However, the molecular mechanisms through which TPM induces weight loss are contradictory and remain to be clarified. Whether TPM treatment alters hypothalamic insulin, or leptin signaling and action, is not well established. Thus, we investigate herein whether short-term TPM treatment alters energy balance by affecting insulin and leptin signaling, action, or neuropeptide expression in the hypothalamus of mice fed with a high-fat diet. As expected, short-term treatment with TPM diminished adiposity in obese mice mainly due to reduced food intake. TPM increased anorexigenic signaling by enhancing the leptin-induced leptin receptor/Janus kinase 2/signal transducer and activator of transcription 3 pathway and the insulin-induced insulin receptor substrate/Akt/forkhead box O1 pathway in parallel to reduced phosphatase protein expression in the hypothalamus of obese mice. These effects were independent of body weight. TPM also raised anorexigenic neuropeptides such as POMC, TRH, and CRH mRNA levels in obese mice. In addition, TPM increased the activation of the hypothalamic MAPK/ERK pathway induced by leptin, accompanied by an increase in peroxisome proliferator-activated receptor-coactivator α and uncoupling protein 1 protein levels in brown adipose tissue. Furthermore, TPM increased AMP-activated protein kinase and acetyl-coenzyme A carboxylase phosphorylation in peripheral tissues, which may help improve energy metabolism in these tissues. Together, these results provide novel insights into the molecular mechanisms through which TPM treatment reduces adiposity.

  20. 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

  1. Morin attenuates hepatic insulin resistance in high-fat-diet-induced obese mice.

    PubMed

    Naowaboot, Jarinyaporn; Wannasiri, Supaporn; Pannangpetch, Patchareewan

    2016-06-01

    Morin is a natural bioflavonoid that exhibits antioxidant and anti-inflammatory properties. The present study was designed to evaluate the effect of morin on insulin resistance, oxidative stress, and inflammation in a high-fat-diet (HFD)-induced obese mice. Obesity was induced in ICR mice by feeding a HFD (60 % kcal from fat) for 12 weeks. After the first 6 weeks, obese mice were treated with morin (50 or 100 mg/kg/day) once daily for further 6 weeks. Blood glucose, lipid profile, insulin, leptin, adiponectin, and markers of oxidative stress and inflammation were then measured. Liver was excised, subjected to histopathology, glycogen determination, and gene and protein expression analysis. Morin administration reduced blood glucose, serum insulin, leptin, malondialdehyde, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) levels and increased serum adiponectin levels. Moreover, there was a reduction in serum lipid and liver triglyceride levels. Liver histology indicated that morin limited accumulation of lipid droplets. Interestingly, morin reduced expression of hepatic sterol regulatory element binding protein 1c (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) and up-regulated hepatic carnitine palmitoyltransferase 1a (CPT1a) expression. Morin also stimulated glycogen storage and suppressed phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) protein expression. Furthermore, hepatic superoxide dismutase (SOD) and catalase (CAT) expression were increased after morin treatment. These findings indicate that morin has a positive effect in the HFD-induced obesity condition by suppressing lipogenesis, gluconeogenesis, inflammation, and oxidative stress activities.

  2. The relation of leptin and insulin with obesity-related cardiovascular risk factors in US adults.

    PubMed

    Reis, Jared P; Macera, Caroline A; Wingard, Deborah L; Araneta, Maria Rosario G; Lindsay, Suzanne P; Marshall, Simon J

    2008-09-01

    Previous studies of leptin with cardiovascular disease (CVD) risk factors have been limited by clinical samples or lack of representation of the general population. This cross-sectional study, designed to examine whether leptin or insulin may mediate the endogenous relation of obesity with metabolic, inflammatory, and thrombogenic cardiovascular risk factors, included 522 men and 514 women aged >or=40 years who completed a physical examination during the third National Health and Nutrition Examination Survey. Participants were free of existing CVD, cancer (except non-melanoma skin cancer), diabetes, or respiratory disease. In multivariable analyses adjusted for race/ethnicity and lifestyle factors, waist circumference (WC) was positively associated with blood pressure, triglyceride, LDL cholesterol, total cholesterol:HDL ratio, apolipoprotein B, C-reactive protein (CRP), and fibrinogen concentrations, and negatively associated with HDL cholesterol and apolipoprotein A1 levels. The associations of WC with the metabolic CVD risk factors were largely attenuated after adjustment for insulin levels, while the associations of WC with the inflammatory and thrombogenic factors (CRP and fibrinogen, respectively) were largely explained by adjustment for leptin concentrations. However, leptin levels were not independently associated with CRP and fibrinogen in men and CRP in women when adjusted for WC. Positive associations of leptin and insulin with fibrinogen in women, independent of WC, were noted. These results suggest that insulin may be an important mediator of the association of obesity with metabolic but not inflammatory or thrombogenic CVD risk factors, while leptin does not appear to influence cardiovascular risk through a shared association with these risk factors. However, we cannot rule out the possibility that leptin and insulin influence cardiovascular risk in women through independent effects on fibrinogen concentrations. PMID:18160070

  3. Nonerythropoietic Erythropoietin-Derived Peptide Suppresses Adipogenesis, Inflammation, Obesity and Insulin Resistance.

    PubMed

    Liu, Yuqi; Luo, Bangwei; Shi, Rongchen; Wang, Jinsong; Liu, Zongwei; Liu, Wei; Wang, Shufeng; Zhang, Zhiren

    2015-10-13

    Erythropoietin (EPO) has been identified as being crucial for obesity modulation; however, its erythropoietic activity may limit its clinical application. EPO-derived Helix B-surface peptide (pHBSP) is nonerythrogenic but has been reported to retain other functions of EPO. The current study aimed to evaluate the effects and potential mechanisms of pHBSP in obesity modulation. We found that pHBSP suppressed adipogenesis, adipokine expression and peroxisome proliferator-activated receptor γ (PPARγ) levels during 3T3-L1 preadipocyte maturation through the EPO receptor (EPOR). In addition, also through EPOR, pHBSP attenuated macrophage inflammatory activation and promoted PPARγ expression. Furthermore, PPARγ deficiency partly ablated the anti-inflammatory activity of pHBSP in macrophages. Correspondingly, pHBSP administration to high-fat diet (HFD)-fed mice significantly improved obesity, insulin resistance (IR) and adipose tissue inflammation without stimulating hematopoiesis. Therefore, pHBSP can significantly protect against obesity and IR partly by inhibiting adipogenesis and inflammation. These findings have therapeutic implications for metabolic disorders, such as obesity and diabetes.

  4. Obesity-induced DNA hypermethylation of the adiponectin gene mediates insulin resistance

    PubMed Central

    Kim, A. Young; Park, Yoon Jeong; Pan, Xuebo; Shin, Kyung Cheul; Kwak, Soo-Heon; Bassas, Abdulelah F.; Sallam, Reem M.; Park, Kyong Soo; Alfadda, Assim A.; Xu, Aimin; Kim, Jae Bum

    2015-01-01

    Adiponectin plays a key role in the regulation of the whole-body energy homeostasis by modulating glucose and lipid metabolism. Although obesity-induced reduction of adiponectin expression is primarily ascribed to a transcriptional regulation failure, the underlying mechanisms are largely undefined. Here we show that DNA hypermethylation of a particular region of the adiponectin promoter suppresses adiponectin expression through epigenetic control and, in turn, exacerbates metabolic diseases in obesity. Obesity-induced, pro-inflammatory cytokines promote DNMT1 expression and its enzymatic activity. Activated DNMT1 selectively methylates and stimulates compact chromatin structure in the adiponectin promoter, impeding adiponectin expression. Suppressing DNMT1 activity with a DNMT inhibitor resulted in the amelioration of obesity-induced glucose intolerance and insulin resistance in an adiponectin-dependent manner. These findings suggest a critical role of adiponectin gene epigenetic control by DNMT1 in governing energy homeostasis, implying that modulating DNMT1 activity represents a new strategy for the treatment of obesity-related diseases. PMID:26139044

  5. [Educational inequality in the occurrence of abdominal obesity according to gender and color/race: the Pro-Health Study, 1999-2001 and 2011-2012].

    PubMed

    Alves, Ronaldo Fernandes Santos; Faerstein, Eduardo

    2016-02-01

    Cross-sectional data from the Pro-Health Study in 1999-2001 and 2011-2012 revealed important gender and color/race differences in the size and variation across time in educational inequalities related to abdominal obesity. Probability of obesity increased steadily in women (independently of color/race) and men (brown/black) with less schooling. These gradients were quantified according to the relative index of inequality (RII). Over the course of the decade, there was a reduction in inequality in brown/black women (ΔRII: 0.5; 95%CI: 0.2-1.1), underlying a relatively higher increase in the prevalence of abdominal obesity in women with more schooling. RII was stable in white women and brown/black men, indicating a similar increase in the prevalence of abdominal obesity in educational subgroups. The association between schooling and abdominal obesity was affected by the multiple interaction of socio-demographic factors. Our results recommend joint stratification by gender and color/race in the study of socioeconomic inequalities related to abdominal obesity.

  6. [Educational inequality in the occurrence of abdominal obesity according to gender and color/race: the Pro-Health Study, 1999-2001 and 2011-2012].

    PubMed

    Alves, Ronaldo Fernandes Santos; Faerstein, Eduardo

    2016-02-01

    Cross-sectional data from the Pro-Health Study in 1999-2001 and 2011-2012 revealed important gender and color/race differences in the size and variation across time in educational inequalities related to abdominal obesity. Probability of obesity increased steadily in women (independently of color/race) and men (brown/black) with less schooling. These gradients were quantified according to the relative index of inequality (RII). Over the course of the decade, there was a reduction in inequality in brown/black women (ΔRII: 0.5; 95%CI: 0.2-1.1), underlying a relatively higher increase in the prevalence of abdominal obesity in women with more schooling. RII was stable in white women and brown/black men, indicating a similar increase in the prevalence of abdominal obesity in educational subgroups. The association between schooling and abdominal obesity was affected by the multiple interaction of socio-demographic factors. Our results recommend joint stratification by gender and color/race in the study of socioeconomic inequalities related to abdominal obesity. PMID:26981869

  7. 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

  8. Obesity, albuminuria and hypertension among Hong Kong Chinese with non-insulin-dependent diabetes mellitus (NIDDM).

    PubMed Central

    Chan, J. C.; Cheung, C. K.; Swaminathan, R.; Nicholls, M. G.; Cockram, C. S.

    1993-01-01

    A total of 412 Hong Kong Chinese diabetic patients were studied on at least two occasions 8-16 weeks apart. Although 28% were insulin-treated, only 3.6% had insulin-dependent diabetes (IDDM). In the remaining 397 patients with non-insulin-dependent diabetes (NIDDM), the mean (s.d.) body mass index (BMI) was 24.4 +/- 3.2 kg/m2 in females and 24.2 +/- 3.2 kg/m2 in males. Obesity was present in 17% of males (BMI > 27 kg/m2) and 40% of females (BMI > 25 kg/m2). Established hypertension was present in 49%. Abnormal albuminuria, defined as a mean urinary albumin/creatinine (UA/Cr) ratio greater than 5.4 mg/mmol based on two random spot urine samples, was present in 47%. On stepwise multiple regression analysis, UA/Cr ratio (R2 = 0.34, F = 65.4, P < 0.001) showed significant associations with systolic blood pressure (standardized regression coefficient beta = 0.40, P < 0.001), plasma creatinine concentration (beta = 0.27, P < 0.001) and glycosylated haemoglobin (beta = 0.20, P < 0.001). While the prevalence of hypertension increased with increasing severity of proteinuria, 40% of normoalbuminuric patients had hypertension. Among patients diagnosed before the age of 35 (n = 67), 52% were insulin-treated although only 10% were insulin-dependent. Among these NIDDM patients of young onset (n = 59), obesity was present in 25% of males and 56% of females. Overall, 18% of these patients had a blood pressure greater than 140/90 mmHg and 27% had abnormal albuminuria. In Hong Kong Chinese, diabetes mellitus is predominantly non-insulin-dependent even in the young. Obesity is more prevalent among females. Abnormal albuminuria is relatively common and is closely associated with hypertension and glycaemic control. In the light of increasing prevalence of diabetes among overseas Chinese, our findings may have important implications in the management of Chinese diabetic patients. PMID:8497435

  9. 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.

  10. 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

  11. RGC32 deficiency protects against high-fat diet-induced obesity and insulin resistance in mice.

    PubMed

    Cui, Xiao-Bing; Luan, Jun-Na; Ye, Jianping; Chen, Shi-You

    2015-02-01

    Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases and many other chronic diseases. Adipose tissue inflammation is a critical link between obesity and insulin resistance and type 2 diabetes and a contributor to disease susceptibility and progression. The objective of this study was to determine the role of response gene to complement 32 (RGC32) in the development of obesity and insulin resistance. WT and RGC32 knockout (Rgc32(-/-) (Rgcc)) mice were fed normal chow or high-fat diet (HFD) for 12 weeks. Metabolic, biochemical, and histologic analyses were performed. 3T3-L1 preadipocytes were used to study the role of RGC32 in adipocytes in vitro. Rgc32(-/-) mice fed with HFD exhibited a lean phenotype with reduced epididymal fat weight compared with WT controls. Blood biochemical analysis and insulin tolerance test showed that RGC32 deficiency improved HFD-induced dyslipidemia and insulin resistance. Although it had no effect on adipocyte differentiation, RGC32 deficiency ameliorated adipose tissue and systemic inflammation. Moreover, Rgc32(-/-) induced browning of adipose tissues and increased energy expenditure. Our data indicated that RGC32 plays an important role in diet-induced obesity and insulin resistance, and thus it may serve as a potential novel drug target for developing therapeutics to treat obesity and metabolic disorders.

  12. Role of Muscle c-Jun NH2-Terminal Kinase 1 in Obesity-Induced Insulin Resistance▿

    PubMed Central

    Sabio, Guadalupe; Kennedy, Norman J.; Cavanagh-Kyros, Julie; Jung, Dae Young; Ko, Hwi Jin; Ong, Helena; Barrett, Tamera; Kim, Jason K.; Davis, Roger J.

    2010-01-01

    Obesity caused by feeding of a high-fat diet (HFD) is associated with an increased activation of c-Jun NH2-terminal kinase 1 (JNK1). Activated JNK1 is implicated in the mechanism of obesity-induced insulin resistance and the development of metabolic syndrome and type 2 diabetes. Significantly, Jnk1−/− mice are protected against HFD-induced obesity and insulin resistance. Here we show that an ablation of the Jnk1 gene in skeletal muscle does not influence HFD-induced obesity. However, muscle-specific JNK1-deficient (MKO) mice exhibit improved insulin sensitivity compared with control wild-type (MWT) mice. Thus, insulin-stimulated AKT activation is suppressed in muscle, liver, and adipose tissue of HFD-fed MWT mice but is suppressed only in the liver and adipose tissue of MKO mice. These data demonstrate that JNK1 in muscle contributes to peripheral insulin resistance in response to diet-induced obesity. PMID:19841069

  13. Role of muscle c-Jun NH2-terminal kinase 1 in obesity-induced insulin resistance.

    PubMed

    Sabio, Guadalupe; Kennedy, Norman J; Cavanagh-Kyros, Julie; Jung, Dae Young; Ko, Hwi Jin; Ong, Helena; Barrett, Tamera; Kim, Jason K; Davis, Roger J

    2010-01-01

    Obesity caused by feeding of a high-fat diet (HFD) is associated with an increased activation of c-Jun NH(2)-terminal kinase 1 (JNK1). Activated JNK1 is implicated in the mechanism of obesity-induced insulin resistance and the development of metabolic syndrome and type 2 diabetes. Significantly, Jnk1(-)(/)(-) mice are protected against HFD-induced obesity and insulin resistance. Here we show that an ablation of the Jnk1 gene in skeletal muscle does not influence HFD-induced obesity. However, muscle-specific JNK1-deficient (M(KO)) mice exhibit improved insulin sensitivity compared with control wild-type (M(WT)) mice. Thus, insulin-stimulated AKT activation is suppressed in muscle, liver, and adipose tissue of HFD-fed M(WT) mice but is suppressed only in the liver and adipose tissue of M(KO) mice. These data demonstrate that JNK1 in muscle contributes to peripheral insulin resistance in response to diet-induced obesity.

  14. 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

  15. Hepatocyte DACH1 is Increased in Obesity Via Nuclear Exclusion of HDAC4 and Promotes Hepatic Insulin Resistance

    PubMed Central

    Ozcan, Lale; Ghorpade, Devram S.; Zheng, Ze; de Souza, Jane Cristina; Chen, Ke; Bessler, Marc; Bagloo, Melissa; Schrope, Beth; Pestell, Richard; Tabas, Ira

    2016-01-01

    SUMMARY Defective insulin signaling in hepatocytes is a key factor in type 2 diabetes. In obesity, activation of calcium/calmodulin-dependent protein kinase II (CaMKII) in hepatocytes suppresses ATF6, which triggers a PERK-ATF4-TRB3 pathway that disrupts insulin signaling. Elucidating how CaMKII suppresses ATF6 is therefore essential to understanding this insulin resistance pathway. We show that CaMKII phosphorylates and blocks nuclear translocation of histone deacetylase 4 (HDAC4). As a result, HDAC4-mediated SUMOylation of the corepressor DACH1 is decreased, which protects DACH1 from proteasomal degradation. DACH1, together with NCOR, represses Atf6 transcription, leading to activation of the PERK-TRB3 pathway and defective insulin signaling. DACH1 is increased in the livers of obese mice and humans, and treatment of obese mice with liver-targeted constitutively-nuclear HDAC4 or DACH1 shRNA increases ATF6, improves hepatocyte insulin signaling, and protects against hyperglycemia and hyperinsulinemia. Thus, DACH1-mediated corepression in hepatocytes emerges as an important link between obesity and insulin resistance. PMID:27239042

  16. 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

  17. 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 ...

  18. Long-term interdisciplinary therapy reduces endotoxin level and insulin resistance in obese adolescents

    PubMed Central

    2012-01-01

    Aim The purpose of the present study was to assess the dietary fat intake, glucose, insulin, Homeostasis model assessment for insulin resistance HOMA-IR, and endotoxin levels and correlate them with adipokine serum concentrations in obese adolescents who had been admitted to long-term interdisciplinary weight-loss therapy. Design The present study was a longitudinal clinical intervention of interdisciplinary therapy. Adolescents (n = 18, aged 15–19 y) with a body mass index > 95th percentile were admitted and evaluated at baseline and again after 1 year of interdisciplinary therapy. We collected blood samples, and IL-6, adiponectin, and endotoxin concentrations were measured by ELISA. Food intake was measured using 3-day diet records. In addition, we assessed glucose and insulin levels as well as the homeostasis model assessment for insulin resistance (HOMA-IR). Results The most important finding from the present investigation was that the long-term interdisciplinary lifestyle therapy decreased dietary fat intake and endotoxin levels and improved HOMA-IR. We observed positive correlations between dietary fat intake and endotoxin levels, insulin levels, and the HOMA-IR. In addition, endotoxin levels showed positive correlations with IL-6 levels, insulin levels and the HOMA-IR. Interestingly, we observed a negative correlation between serum adiponectin and both dietary fat intake and endotoxin levels. Conclusions The present results indicate an association between dietary fat intake and endotoxin level, which was highly correlated with a decreased pro-inflammatory state and an improvement in HOMA-IR. In addition, this benefits effect may be associated with an increased adiponectin level, which suggests that the interdisciplinary therapy was effective in improving inflammatory pathways. PMID:22989045

  19. 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. PMID:27496224

  20. Comparison of robot-assisted total laparoscopic hysterectomy and total abdominal hysterectomy for treatment of endometrial cancer in obese and morbidly obese patients.

    PubMed

    Nevadunsky, N; Clark, R; Ghosh, S; Muto, M; Berkowitz, R; Vitonis, A; Feltmate, C

    2010-12-01

    The objective of our study was to compare clinical and pathologic outcomes of robot-assisted and open abdominal techniques for treatment of uterine cancer in obese patients. Institutional review board approval was obtained. Patient demographic data, pathological data, and surgical data were collected by retrospective chart review. Data were analyzed using SAS statistical software. One-hundred and eighty-nine consecutive cases of suspected uterine cancer were identified from October 2003 until January 2009. Of these, 116 patients (61%) had a body mass index (BMI) over 30. There were 66 completed robot-assisted hysterectomies (RAHs), 43 total abdominal hysterectomies (TAHs), and seven patients that were converted from RAH to open abdominal hysterectomy. There were no significant differences in preoperative patient demographics, including body mass index (BMI), medical co-morbidities, or preoperative cytology, except for parity. There were no differences in postoperative grade, stage, lymph vascular space invasion, positive pelvic washings, mean number of pelvic lymph nodes, or proportion of patients undergoing pelvic lymphadenectomy. Length of stay and estimated blood loss were lower for the robotic technique; RAHs had a significantly longer operative time, however. Postoperative blood transfusions and wound infections were more frequent in the TAH group. Of the RAH group there were seven conversions to TAH (10%). Differences in surgical times with and without lymphadenectomy were least in patients in the largest BMI category of >50. Length of time required for RAH was significantly longer then TAH in obese and morbidly obese patients, however benefits to patients of a minimally invasive approach included reduced incidence of wound infections, reduced transfusion rates, reduced blood loss, and shortened length of stay. These data also suggest the greatest advantage of robotic technology over laparotomy in patients with BMI over 50. PMID:27627953

  1. Transient increase in obese gene expression after food intake or insulin administration.

    PubMed

    Saladin, R; De Vos, P; Guerre-Millo, M; Leturque, A; Girard, J; Staels, B; Auwerx, J

    1995-10-12

    Obesity is a disorder of energy balance, indicating a chronic disequilibrium between energy intake and expenditure. Recently, the mouse ob gene, and subsequently its human and rat homologues, have been cloned. The ob gene product, leptin, is expressed exclusively in adipose tissue, and appears to be a signalling factor regulating body-weight homeostasis and energy balance. Because the level of ob gene expression might indicate the size of the adipose depot, we suggest that it is regulated by factors modulating adipose tissue size. Here we show that ob gene exhibits diurnal variation, increasing during the night, after rats start eating. This variation was linked to changes in food intake, as fasting prevented the cyclic variation and decreased ob messenger RNA. Furthermore, refeeding fasted rats restored ob mRNA within 4 hours to levels of fed animals. A single insulin injection in fasted animals increased ob mRNA to levels of fed controls. Experiments to control glucose and insulin independently in animals, and studies in primary adipocytes, showed that insulin regulates ob gene expression directly in rats, regardless of its glucose-lowering effects. Whereas the ob gene product, leptin, has been shown to reduce food intake and increase energy expenditure, our data demonstrate that ob gene expression is increased after food ingestion in rats, perhaps through a direct action of insulin on the adipocyte.

  2. The Obesity-Linked Gene Nudt3 Drosophila Homolog Aps Is Associated With Insulin Signaling.

    PubMed

    Williams, Michael J; Eriksson, Anders; Shaik, Muksheed; Voisin, Sarah; Yamskova, Olga; Paulsson, Johan; Thombare, Ketan; Fredriksson, Robert; Schiöth, Helgi B

    2015-09-01

    Several genome-wide association studies have linked the Nudix hydrolase family member nucleoside diphosphate-linked moiety X motif 3 (NUDT3) to obesity. However, the manner of NUDT3 involvement in obesity is unknown, and NUDT3 expression, regulation, and signaling in the central nervous system has not been studied. We performed an extensive expression analysis in mice, as well as knocked down the Drosophila NUDT3 homolog Aps in the nervous system, to determine its effect on metabolism. Detailed in situ hybridization studies in the mouse brain revealed abundant Nudt3 mRNA and protein expression throughout the brain, including reward- and feeding-related regions of the hypothalamus and amygdala, whereas Nudt3 mRNA expression was significantly up-regulated in the hypothalamus and brainstem of food-deprived mice. Knocking down Aps in the Drosophila central nervous system, or a subset of median neurosecretory cells, known as the insulin-producing cells (IPCs), induces hyperinsulinemia-like phenotypes, including a decrease in circulating trehalose levels as well as significantly decreasing all carbohydrate levels under starvation conditions. Moreover, lowering Aps IPC expression leads to a decreased ability to recruit these lipids during starvation. Also, loss of neuronal Aps expression caused a starvation susceptibility phenotype while inducing hyperphagia. Finally, the loss of IPC Aps lowered the expression of Akh, Ilp6, and Ilp3, genes known to be inhibited by insulin signaling. These results point toward a role for this gene in the regulation of insulin signaling, which could explain the robust association with obesity in humans.

  3. Vitamin D status and insulin resistance among young obese Saudi females

    PubMed Central

    Abdelkarem, Hala M.; El-Sherif, Mervat A.; Gomaa, Sahar B.

    2016-01-01

    Objectives: To evaluate the association of vitamin D level with insulin resistance, among healthy student’s obese women, and to identify factors that may elucidate this association. Methods: One hundred and forty-seven female students between the age group of 18 and 25 years were included in this cross-sectional study, and the related socio-demographic and anthropometric data were obtained. They were selected randomly from Aljouf University, Sakaka, Saudi Arabia between November 2013 and June 2014. Serum 25-hydroxy vitamin D (25[OH]D), glucose, insulin was measured and insulin resistance was calculated using the insulin resistance index (HOMA-IR). Results: The results showed the percentage of 25[OH]D concentration in female students was 21.3% sufficient, 59.6% mild deficiency, and 19.3% moderate deficiency. The percentage of waist circumferences (WC) were 41.3% (>88 cm) and 58.7% (<88 cm), body mass index (BMI) was 13.6% (obese) and 31.8% (over weight), blood pressure (BP) was 65.7% (<130/85 mm Hg), and 33.2% (>130/85 mm Hg). Based on the cut-off point of 25[OH]D, 17.4% of females had 25[OH]D deficiency, 27.3% insufficient, and 55.3% sufficient. When the females were classified according to the BMI category, the serum 25[OH]D concentrations for obese was the lowest value (54.6%) when compared with the overweight (31.8%) and normal weight (0.9%). 25[OH]D was inversely associated with BMI, fat%, and HOMA-IR. Conclusion: Our results suggest that vitamin D deficiency is prevalent in women of Saudi who are university students especially in those who are obese. Preventive interventions in order to reduce the tendency of deficiency among college students should focus on the awareness of the essentiality of vitamin D promotion of direct exposure to sunlight (vitamin D3) and consumption of vitamin D fortified food as a part of Saudi diets. PMID:27146620

  4. 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

  5. Association of Smoking in Adolescence With Abdominal Obesity in Adulthood: A Follow-Up Study of 5 Birth Cohorts of Finnish Twins

    PubMed Central

    Pietiläinen, Kirsi; Kantonen, Suvi; Rissanen, Aila; Kaprio, Jaakko

    2009-01-01

    Objectives. We studied the association of adolescent smoking with overweight and abdominal obesity in adulthood. Methods. We used the FinnTwin16, a prospective, population-based questionnaire study of 5 consecutive and complete birth cohorts of Finnish twins born between 1975 and 1979 (N = 4296) and studied at four points between the ages of 16 and 27 years to analyze the effect of adolescent smoking on abdominal obesity and overweight in early adulthood. Results. Smoking at least 10 cigarettes daily when aged 16 to 18 years increased the risk of adult abdominal obesity (odds ratio [OR]=1.77; 95% confidence interval [CI] = 1.39, 2.26). After we adjusted for confounders, the OR was 1.44 (95% CI = 1.11, 1.88), and after further adjustment for current body mass index (BMI), the OR was 1.34 (95% CI = 0.95, 1.88). Adolescent smoking significantly increased the risk of becoming overweight among women even after adjustment for possible confounders, including baseline BMI (OR = 1.74; 95% CI = 1.06, 2.88). Conclusions. Smoking is a risk factor for abdominal obesity among both genders and for overweight in women. The prevention of smoking during adolescence may play an important role in promoting healthy weight and in decreasing the morbidity related to abdominal obesity. PMID:19059868

  6. 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. PMID:27525284

  7. 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.

  8. 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

  9. Using Metabolomic Profiles as Biomarkers for Insulin Resistance in Childhood Obesity: A Systematic Review.

    PubMed

    Zhao, Xue; Gang, Xiaokun; Liu, Yujia; Sun, Chenglin; Han, Qing; Wang, Guixia

    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

  10. 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

  11. 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

  12. Accumulation of triglyceride-rich lipoprotein in subjects with abdominal obesity: the biguanides and the prevention of the risk of obesity (BIGPRO) 1 study.

    PubMed

    Bard, J M; Charles, M A; Juhan-Vague, I; Vague, P; André, P; Safar, M; Fruchart, J C; Eschwege, E

    2001-03-01

    The present study represents a new insight into the Biguanides and the Prevention of the Risk of Obesity (BIGPRO) 1 study population at inclusion. This population, selected basically on the basis of a high waist-to-hip ratio (>/=0.95 for men and >/=0.80 for women), is supposed to represent a group of patients with insulin resistance. The present study was undergone to establish whether apolipoprotein C-III (apoC-III) and apolipoprotein E (apoE) associated with apo B (apoC-III LpB and apoE LpB, respectively), considered to be markers of remnant accumulation, play a role in the hypertriglyceridemia associated with insulin resistance and whether they are related to other biological abnormalities frequently observed in this syndrome. In this population, the concentration of the markers of remnant accumulation increases with triglyceride levels. Therefore, correlation studies were realized to assess the relative effect of insulin and the markers of remnant accumulation on triglyceride plasma level. As a first attempt, a simple correlation analysis revealed that insulin is positively related to the markers of remnant accumulation only in hypertriglyceridemic patients (triglycerides >/=1.7 mmol/L). To assess the independent contribution of these markers, insulin, and other parameters related to the plasma triglyceride concentration, a stepwise multiple regression analysis was run. Results revealed that insulin and the markers of remnant accumulation (specifically, apoE LpB) are independent contributors to the plasma triglyceride concentration. Markers of the endothelial damage, plasminogen activator inhibitor-1, tissue plasminogen activator, and von Willebrand factor, which are often increased in the case of insulin resistance, were tested for their correlation with the markers of remnant accumulation. Plasminogen activator inhibitor-1 is positively correlated with these markers only in hypertriglyceridemic male subjects. It is concluded that increased insulin levels

  13. The interaction between the interleukin 6 receptor gene genotype and dietary energy intake on abdominal obesity in Japanese men.

    PubMed

    Song, Yixuan; Miyaki, Koichi; Araki, Jungo; Zhang, Ling; Omae, Kazuyuki; Muramatsu, Masaaki

    2007-07-01

    Previous reports have shown that the Asp358Ala (T/G) polymorphism of the interleukin 6 receptor (IL6R) gene is associated with obesity and type 2 diabetes mellitus, but few studies have examined this association in the Japanese population. We performed the current study to investigate the relationship between the IL6R Asp358Ala (T/G) polymorphism and obesity in healthy Japanese men. Two hundred eighty-five healthy Japanese men (age, 46.1 +/- 11.5 years [mean +/- SD]; waist circumference [WC], 83.9 +/- 9.3 cm; body mass index, 23.3 +/- 3.3 kg/m(2)) employed by a Japanese company were enrolled in this study. Height, weight, and WC were measured, and daily energy intake levels were assessed by self-reported questionnaires. Genotyping of polymorphisms was performed by using melting curve analysis; no association was found between IL6R genotype and WC or body mass index. However, when the subjects were stratified by IL6R genotype, an association between WC and dietary energy intake level was found in the TT + GT-type subjects (P for linear regression = .048), but not in GG subjects (P for linear regression = .555). In addition, logistic regression analysis revealed that the interaction of IL6R (GG vs TT + GT) genotypes and dietary energy intake levels affected risk for abdominal obesity (P for interaction = .030). We concluded that the IL6R Asp358Ala (T/G) polymorphism appears to interact with energy intake and affect abdominal obesity in Japanese men. The interaction of this genotype and energy intake warrants further study.

  14. 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.

  15. The Combined Effects of Obesity, Abdominal Obesity and Major Depression/Anxiety on Health-Related Quality of Life: the LifeLines Cohort Study

    PubMed Central

    Nigatu, Yeshambel T.; Reijneveld, Sijmen A.; de Jonge, Peter; van Rossum, Elisabeth; Bültmann, Ute

    2016-01-01

    Background Obesity and major depressive disorder (MDD)/anxiety disorders often co-occur and aggravate each other resulting in adverse health-related outcomes. As little is known about the potential effects of interaction between obesity and MDD and/or anxiety disorders on health-related quality of life (HR-QoL), this study was aimed at examining these combined effects. Methods We collected data among N = 89,332 participants from the LifeLines cohort study. We categorized body weight using body mass index (kg/m2) as normal weight (18.5–24.99), overweight (25–29.9), mild obesity (30–34.9) and moderate/severe obesity (≥ 35); we measured abdominal obesity using a waist circumference of ≥102 and ≥ 88 cm for males and females, respectively. MDD and anxiety disorders were diagnosed with the Mini-International Neuropsychiatric Interview. HR-QoL was assessed using the RAND-36 questionnaire to compute physical and mental quality of life scores. We used binary logistic and linear regression analyses. Results The combined effect of obesity and MDD and/or anxiety disorders on physical QoL was larger than the sum of their separate effects; regression coefficients, B (95%-confidence interval, 95%-CI) were: - 1.32 (-1.75; -0.90). However, the combined effect of obesity and major depression alone on mental QoL was less than the additive effect. With increasing body weight participants report poorer physical QoL; when they also have MDD and/or anxiety disorders participants report even poorer physical QoL. In persons without MDD and/or anxiety disorders, obesity was associated with a better mental QoL. Conclusions Obesity and MDD and/or anxiety disorders act synergistically on physical and mental QoL. The management of MDD and/or anxiety disorders and weight loss may be important routes to improve HR-QoL. PMID:26866920

  16. [The interconnections of molecular mechanisms of hormone actions and their role in pathogenesis of obesity, insulin resistance, and diabetes mellitus].

    PubMed

    Pankov, Iu A; Chekhranova, M K; Karpova, S K

    2008-01-01

    The various hormones, proteins and other compounds related to developing obesity, insulin resistance and type 2 diabetes are analyzed in the paper. 1) Leptin, ciliary neurutrophic factor, adiponectin, glucagon-like peptide 1, peptide YY, neuromedin S, as well as the protein receptors of these hormones decrease the food consumption, increase the energy turnover, and prevent obesity, insulin resistance, and type 2 diabetes development. The mediators of these hormone and receptor actions are melanocyte stimulating hormone (MSH), corticotropin-releasing hormone (CRH), and the others. 2) Ghrelin, endogenose cannabinoides, galanin-like peptide and the mediators of their actions: neuropeptide Y (NPY) and Agouti gene related protein (AGRP) increase the appetite and food consumption. Peroxisome proliferation-activated receptor (PPAR) performs the similar action on food intake. The activation of the first group compound functioning decreases the obesity, increases the energy turnover, facilitates the insulin action and prevents the insulin resistance and type 2 diabetes. Increasing the activities of the second group, as well as, decreasing the actions of the first one of substances induce the opposite effects and facilitate obesity, insulin resistance, and type 2 diabetes developments. The interconnections of the molecular mechanisms of so many hormone actions make the very complicated tusk to study the various endocrine disorders including diabetes mellitus as well.

  17. High Physiological Omega-3 Fatty Acid Supplementation Affects Muscle Fatty Acid Composition and Glucose and Insulin Homeostasis in Obese Adolescents

    PubMed Central

    Dangardt, Frida; Chen, Yun; Gronowitz, Eva; Dahlgren, Jovanna; Friberg, Peter; Strandvik, Birgitta

    2012-01-01

    Obese adolescents have high concentrations of saturated fatty acids and low omega-3 long-chain polyunsaturated fatty acids (LCUFAs) in plasma phospholipids. We aimed to investigate effects of omega-3 LCPUFA supplementation to obese adolescents on skeletal muscle lipids and glucose and insulin homeostasis. Twenty-five obese adolescents (14–17 years old, 14 females) completed a randomized double-blind crossover study supplying capsules containing either 1.2 g omega-3 LCPUFAs or placebo, for 3 months each with a six-week washout period. Fasting blood glucose, insulin, leptin, adiponectin, and lipids were measured. Intravenous glucose tolerance test (IVGTT) and euglycemic-hyperinsulinemic clamp were performed, and skeletal muscle biopsies were obtained at the end of each period. The concentrations of EPA, DHA, and total omega-3 PUFA in muscle phospholipids increased in both sexes. In the females, omega-3 LCPUFA supplementation improved glucose tolerance by 39% (P = 0.04) and restored insulin concentration by 34% (P = 0.02) during IVGTT. Insulin sensitivity improved 17% (P = 0.07). In males, none of these parameters was influenced by omega-3 supplementation. Thus, three months of supplementation of omega-3 LCPUFA improved glucose and insulin homeostasis in obese girls without influencing body weight. PMID:22523671

  18. Genetic ablation of lymphocytes and cytokine signaling in nonobese diabetic mice prevents diet-induced obesity and insulin resistance.

    PubMed

    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

    2016-03-01

    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.

  19. Relation between Delayed Superfluous Insulin Secretion during An Oral Glucose Tolerance Test and Metabolic Disorders in Obese Japanese Children.

    PubMed

    Sato, Hidetoshi; Kikuchi, Toru; Harada, Waka; Yoshida, Hiroshi; Ito, Sueshi; Uchiyama, Makoto

    2011-04-01

    The aim of this study was to clarify the relation between postprandial hyperinsulinemia and metabolic disorders in obese children. Twenty-eight obese Japanese children (8.8-16.2 yr) were divided into four groups: without impaired liver function and dyslipidemia (Group A), with impaired liver function (Group B), with dyslipidemia (Group C), and with impaired liver function and dyslipidemia (Group D). The levels of PG, serum immunoreactive insulin (IRI) and serum C-peptide (CPR) were measured during an oral glucose tolerance test (OGTT). The subjects had delayed superfluous insulin and CPR secretion during the OGTT compared with healthy references. In regard to the insulin secretion pattern, Group A's response peaked at 60 min and then decreased gradually until 120 min, Group B's response peaked at 60 min, remained at the peak until 120 min and then decreased gradually until 180 min, Group C's response peaked at 120 min and then decreased gradually until 180 min, and Group D's response peaked at 120 min and remained at the peak until 180 min. These results suggest that delayed superfluous insulin secretion during an OGTT is related to metabolic disorders in obese Japanese children and that these patients will experience a vicious cycle of postprandial hyperinsulinemia and metabolic disorders. It is important to prevent healthy children from becoming obese and to improve management of childhood obesity.

  20. Does Insulin Explain the Relation between Maternal Obesity and Poor Lactation Outcomes? An Overview of the Literature.

    PubMed

    Nommsen-Rivers, Laurie A

    2016-03-01

    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

  1. Resistance training improves indices of muscle insulin sensitivity and β-cell function in overweight/obese, sedentary young men

    PubMed Central

    Croymans, Daniel M.; Paparisto, Ergit; Lee, Mary M.; Brandt, Nina; Le, Brian K.; Lohan, Derek; Lee, Cathy C.

    2013-01-01

    We examined the effects of RT on oral glucose tolerance test (OGTT)-derived indices of muscle insulin sensitivity, hepatic insulin resistance, β-cell function, and skeletal muscle proteins related to glucose transport in overweight/obese, sedentary young men. Twenty-eight participants [median body mass index (BMI) 30.9 kg/m2; age 22 yr] completed 12 wk of RT (3 sessions/wk) and were assessed for changes in OGTT-derived indices, resting metabolic rate, body composition, serum adipokines, and skeletal muscle protein content [hexokinase 2 (HK2), glucose transporter type 4 (GLUT4), RAC-β serine/threonine-protein kinase (AKT2), glycogen synthase kinase 3β, and insulin receptor substrate 1]. Individualized responses to RT were also evaluated. RT significantly improved insulin and glucose area under the curve (both P < 0.03). With the use of OGTT indices of insulin action, we noted improved muscle insulin sensitivity index (mISI; P = 0.03) and oral disposition index (P = 0.03). BMI, lean body mass (LBM), and relative strength also increased (all P < 0.03), as did skeletal muscle protein content of HK2, GLUT4, and AKT2 (26–33%; all P < 0.02). Hepatic insulin resistance index, adiponectin, leptin, and total amylin did not change. Further analysis demonstrated the presence of highly individualized responsiveness to RT for glucose tolerance and other outcomes. RT improved oral indices of muscle insulin sensitivity and β-cell function but not hepatic insulin resistance in overweight/obese young men. In addition to the increase in LBM, the improvements in insulin action may be due, in part, to increases in key insulin signaling proteins. PMID:23970530

  2. Nobiletin improves hyperglycemia and insulin resistance in obese diabetic ob/ob mice.

    PubMed

    Lee, Young-Sil; Cha, Byung-Yoon; Saito, Kiyoto; Yamakawa, Hiroshi; Choi, Sun-Sil; Yamaguchi, Kohji; Yonezawa, Takayuki; Teruya, Toshiaki; Nagai, Kazuo; Woo, Je-Tae

    2010-06-01

    Nobiletin is a polymethoxylated flavone found in certain citrus fruits that exhibits various pharmacological effects including anti-inflammatory, antitumor and neuroprotective properties. The present study investigated the effects of nobiletin on insulin sensitivity in obese diabetic ob/ob mice, and the possible mechanisms involved. The ob/ob mice were treated with nobiletin (200mg/kg) for 5 weeks. Nobiletin significantly improved the plasma glucose levels, homeostasis model assessment index, glucose tolerance in an oral glucose tolerance test and plasma adiponectin levels. In white adipose tissue (WAT), nobiletin significantly decreased the mRNA expression levels of inflammatory adipokines such as interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 and increased the mRNA expression levels of adiponectin, peroxisome proliferator-activated receptor (PPAR)-gamma and its target genes. At the same time, nobiletin increased the glucose transporter (Glut) 4 expression levels in the whole plasma membrane, and Glut1 and phospho-Akt expression in the whole cell lysates in WAT and muscle. Nobiletin also increased Glut4 protein expression level in the whole cell lysates of the muscle. Taken together, the present results suggest that nobiletin improved the hyperglycemia and insulin resistance in obese diabetic ob/ob mice by regulating expression of Glut1 and Glut4 in WAT and muscle, and expression of adipokines in WAT.

  3. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines.

    PubMed

    Makki, Kassem; Froguel, Philippe; Wolowczuk, Isabelle

    2013-12-22

    Adipose tissue is a complex organ that comprises a wide range of cell types with diverse energy storage, metabolic regulation, and neuroendocrine and immune functions. Because it contains various immune cells, either adaptive (B and T lymphocytes; such as regulatory T cells) or innate (mostly macrophages and, more recently identified, myeloid-derived suppressor cells), the adipose tissue is now considered as a bona fide immune organ, at the cross-road between metabolism and immunity. Adipose tissue disorders, such as those encountered in obesity and lipodystrophy, cause alterations to adipose tissue distribution and function with broad effects on cytokine, chemokine, and hormone expression, on lipid storage, and on the composition of adipose-resident immune cell populations. The resulting changes appear to induce profound consequences for basal systemic inflammation and insulin sensitivity. The purpose of this review is to synthesize the current literature on adipose cell composition remodeling in obesity, which shows how adipose-resident immune cells regulate inflammation and insulin resistance-notably through cytokine and chemokine secretion-and highlights major research questions in the field.

  4. 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. PMID:26512025

  5. 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

  6. Physical activity-induced improvements in markers of insulin resistance in overweight and obese children and adolescents.

    PubMed

    Tompkins, Connie L; Moran, Kelsey; Preedom, Stephanie; Brock, David W

    2011-05-01

    Childhood obesity is a significant, worldwide, public health problem. Coinciding with the increasing prevalence of obesity in youth, Type 2 diabetes has emerged as a critical health condition in this population. In the U.S. alone, approximately 215,000 U.S. youth under the age of 20 were diagnosed with diabetes, with the majority of 10-19 years old diagnosed with Type 2 diabetes. Additionally, the exact number of youth that may have Type 2 diabetes yet remain undiagnosed is unknown. Increasing physical activity to encourage weight loss among youth may reduce the incidence of Type 2 diabetes in youth; however, several recent studies reported positive associations between physical activity and components of Type 2 diabetes without weight loss in youth. These findings support previous studies in adults which observed physical activity-induced improvements in insulin dynamics without changes in body fat. The purpose of this review was to identify studies which examined the effect of physical activity without dietary intervention on markers of insulin resistance in overweight and obese youth. These studies provide strong evidence that physical activity alone, without dietary intervention, can have a positive, significant impact on insulin resistance risk and potentially prevent the development of type 2 diabetes in overweight and obese youth. The studies reviewed provide support for future interventions to shift the focus from reducing obesity to increasing physical activity for the prevention of type 2 diabetes in obese youth.

  7. 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

  8. Negative association between trunk fat, insulin resistance and skeleton in obese women

    PubMed Central

    Greco, Emanuela A; Francomano, Davide; Fornari, Rachele; Marocco, Chiara; Lubrano, Carla; Papa, Vincenza; Wannenes, Francesca; Di Luigi, Luigi; Donini, Lorenzo M; Lenzi, Andrea; Aversa, Antonio; Migliaccio, Silvia

    2013-01-01

    AIM: To evaluate the potential interference of trunk fat (TF) mass on metabolic and skeletal metabolism. METHODS: In this cross-sectional study, 340 obese women (mean age: 44.8 ± 14 years; body mass index: 36.0 ± 5.9 kg/m2) were included. Patients were evaluated for serum vitamin D, osteocalcin (OSCA), inflammatory markers, lipids, glucose and insulin (homeostasis model assessment of insulin resistance, HOMA-IR) levels, and hormones profile. Moreover, all patients underwent measurements of bone mineral density (BMD; at lumbar and hip site) and body composition (lean mass, total and trunk fat mass) by dual-energy X-ray absorptiometry. RESULTS: Data showed that: (1) high TF mass was inversely correlated with low BMD both at lumbar (P < 0.001) and hip (P < 0.01) sites and with serum vitamin D (P < 0.0005), OSCA (P < 0.0001) and insulin-like growth factor-1 (IGF-1; P < 0.0001) levels; (2) a positive correlation was found between TF and HOMA-IR (P < 0.01), fibrinogen (P < 0.0001) and erythrocyte sedimentation rate (P < 0.0001); (3) vitamin D levels were directly correlated with IGF-1 (P < 0.0005), lumbar (P < 0.006) and hip (P < 0.01) BMD; and (4) inversely with HOMA-IR (P < 0.001) and fibrinogen (P < 0.0005).Multivariate analysis demonstrated that only vitamin D was independent of TF variable. CONCLUSION: In obese women, TF negatively correlates with BMD independently from vitamin D levels. Reduced IGF-1 and increased inflammatory markers might be some important determinants that account for this relationship. PMID:23593534

  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. PMID:24272914

  10. High fat diet induces central obesity, insulin resistance and microvascular dysfunction in hamsters.

    PubMed

    Costa, Rute R S; Villela, Nivaldo Ribeiro; Souza, Maria das Graças C; Boa, Beatriz C S; Cyrino, Fátima Z G A; Silva, Simone V; Lisboa, Patricia C; Moura, Egberto G; Barja-Fidalgo, Thereza Christina; Bouskela, Eliete

    2011-11-01

    Microvascular dysfunction is an early finding in obesity possibly related to co-morbidities like diabetes and hypertension. Therefore we have investigated changes on microvascular function, body composition, glucose and insulin tolerance tests (GTT and ITT) on male hamsters fed either with high fat (HFD, n=20) or standard (Control, n=21) diet during 16 weeks. Total body fat and protein content were determined by carcass analysis, aorta eNOS and iNOS expression by immunoblotting assay and mean blood pressure (MAP) and heart rate (HR) by an arterial catheter. Microvascular reactivity in response to acetylcholine and sodium nitroprusside, functional capillary density (FCD), capillary recruitment induced by a hyperinsulinemic status and macromolecular permeability after 30 min ischemia was assessed on either cheek pouch or cremaster muscle preparations. Compared to Control, HFD animals have shown increased visceral fat (6.0 ± 0.8 vs. 13.8 ± 0.6g/100g BW), impaired endothelial dependent vasodilatation, decreased FCD (11.3 ± 1.3 vs. 6.8 ± 1.2/field) and capillary recruitment during hyperinsulinemia and increased macromolecular permeability after ischemia/reperfusion (86.4 ± 5.2 vs.105.2 ± 5.1 leaks/cm(2)), iNOS expression and insulin resistance. MAP, HR, endothelial independent vasodilatation and eNOS expression were not different between groups. Our results have shown that HFD elicits an increase on visceral fat deposition, microvascular dysfunction and insulin resistance in hamsters.

  11. 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

  12. Decaffeinated Green Coffee Bean Extract Attenuates Diet-Induced Obesity and Insulin Resistance in Mice

    PubMed Central

    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. PMID:24817902

  13. 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

  14. 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. PMID:24817902

  15. 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.

  16. 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.

  17. Relationships among obesity, inflammation, and insulin resistance in African Americans and West Africans.

    PubMed

    Doumatey, Ayo P; Lashley, Kerrie S; Huang, Hanxia; Zhou, Jie; Chen, Guanjie; Amoah, Albert; Agyenim-Boateng, Kofi; Oli, Johnnie; Fasanmade, Olufemi; Adebamowo, Clement A; Adeyemo, Adebowale A; Rotimi, Charles N

    2010-03-01

    Several research studies in different populations indicate that inflammation may be the link between obesity and insulin resistance (IR). However, this relationship has not been adequately explored among African Americans, an ethnic group with disproportionately high rates of obesity and IR. In this study, we conducted a comparative study of the relationship among adiposity, inflammation, and IR in African Americans and West Africans, the ancestral source population for African Americans. The associations between obesity markers (BMI and waist-to-hip ratio (WHR)), inflammatory markers (high-sensitivity C-reactive protein (hsCRP), haptoglobin, interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha), and IR (homeostasis model assessment of insulin resistance (HOMA(IR))) were evaluated in 247 West Africans and 315 African Americans. In average, African Americans were heavier than the West Africans (by an average of 1.6 BMI units for women and 3 BMI units for men). Plasma hsCRP, haptoglobin, and IL-6 (but not TNF-alpha level) were higher in African Americans than in West Africans. In both populations, BMI was associated with markers of inflammation and with HOMA(IR), and these associations remained significant after adjusting for sex and age. However, the pattern of associations between measured inflammatory markers and IR was different between the two groups. In West Africans, hsCRP was the only inflammatory marker associated with IR. In contrast, hsCRP, haptoglobin, and IL-6 were all associated with IR in African Americans. Interestingly, none of the associations between markers of inflammation and IR remained significant after adjusting for BMI. This finding suggests that in African Americans, the relationship between inflammatory markers and IR is mediated by adiposity.

  18. 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.

  19. Loss of intestinal GATA4 prevents diet-induced obesity and promotes insulin sensitivity in mice

    PubMed Central

    Patankar, Jay V.; Chandak, Prakash G.; Obrowsky, Sascha; Pfeifer, Thomas; Diwoky, Clemens; Uellen, Andreas; Sattler, Wolfgang; Stollberger, Rudolf; Hoefler, Gerald; Heinemann, Akos; Battle, Michele; Duncan, Stephen; Kratky, Dagmar

    2011-01-01

    Transcriptional regulation of small intestinal gene expression controls plasma total cholesterol (TC) and triglyceride (TG) levels, which are major determinants of metabolic diseases. GATA4, a zinc finger domain transcription factor, is critical for jejunal identity, and intestinal GATA4 deficiency leads to a jejunoileal transition. Although intestinal GATA4 ablation is known to misregulate jejunal gene expression, its pathophysiological impact on various components of metabolic syndrome remains unknown. Here, we used intestine-specific GATA4 knockout (GATA4iKO) mice to dissect the contribution of GATA4 on obesity development. We challenged adult GATA4iKO mice and control littermates with a Western-type diet (WTD) for 20 wk. Our findings show that WTD-fed GATA4iKO mice are resistant to diet-induced obesity. Accordingly, plasma TG and TC levels are markedly decreased. Intestinal lipid absorption in GATA4iKO mice was strongly reduced, whereas luminal lipolysis was unaffected. GATA4iKO mice displayed a greater glucagon-like peptide-1 (GLP-1) release on normal chow and even after long-term challenge with WTD remained glucose sensitive. In summary, our findings show that the absence of intestinal GATA4 has a beneficial effect on decreasing intestinal lipid absorption causing resistance to hyperlipidemia and obesity. In addition, we show that increased GLP-1 release in GATA4iKO mice decreases the risk for development of insulin resistance. PMID:21177287

  20. Bif-1 deficiency impairs lipid homeostasis and causes obesity accompanied by insulin resistance

    PubMed Central

    Liu, Ying; Takahashi, Yoshinori; Desai, Neelam; Zhang, Jun; Serfass, Jacob M.; Shi, Yu-Guang; Lynch, Christopher J.; Wang, Hong-Gang

    2016-01-01

    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. PMID:26857140

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

    PubMed

    Picklo, Matthew J; Thyfault, John P

    2015-04-01

    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.

  2. 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

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

    PubMed

    Picklo, Matthew J; Thyfault, John P

    2015-04-01

    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

  4. 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.

  5. Obesity independently predicts responders to biphasic insulin 50/50 (Humalog Mix50 and Insuman Comb 50) following conversion from other insulin regimens: a retrospective cohort study

    PubMed Central

    Mamza, J; Mehta, R; Idris, I

    2014-01-01

    Aims This study aims to examine the metabolic effects of intensification or initiation of insulin treatment with biphasic insulin 50/50, and determine the predictors of responders or non-responders to biphasic insulin 50/50. Methods A cohort of 2183 patients ≥18 years with diabetes, newly treated with biphasic insulin 50/50 between January 2000 and May 2012, were sourced from UK General Practices via The Health Improvement Network (THIN) database. Baseline clinical parameters of 1267 patients with suboptimal glycated hemoglobin (HbA1c) >7.5% (>58 mmol/mol) who had received background insulin regimens for at least 6 months preceding biphasic insulin 50/50 were compared against 12-month outcome data. Responders were defined as those with HbA1c <7.5% (58 mmol/mol) and/or HbA1c reduction of ≥1% (10.9 mmol/mol) at 12 months. Comparative analyses were carried out on subgroups of 237 patients initiating insulin therapy with biphasic insulin 50/50, and between users of the Humalog Mix50 (HM50) versus Insuman Comb 50 (IC50). Associations were examined using t tests and multivariate logistic regression techniques. Results The overall mean HbA1c reduction at 12 months as a result of intensification and initiation with biphasic insulin 50/50 was 0.5% (5.5 mmol/mol) and 1.6% (17.5 mmol/mol), respectively. Adjusted ORs show obesity (body mass index >30 kg/m2), treatment duration for ≥9 months, and baseline HbA1c are independent determinants of responders. In addition, stratified for baseline HbA1c levels, HM50 was associated with better HbA1c outcome compared with IC50. Conclusions biphasic insulin 50/50 is effective for achieving glycemic control in suboptimal HbA1c levels, especially among obese patients with insulin-treated diabetes. Stratified for baseline HbA1c, HM50 was associated with improved HbA1c outcome compared with IC50. PMID:25452865

  6. 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

  7. Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats.

    PubMed

    Banin, R M; Hirata, B K S; Andrade, I S; Zemdegs, J C S; Clemente, A P G; Dornellas, A P S; Boldarine, V T; Estadella, D; Albuquerque, K T; Oyama, L M; Ribeiro, E B; Telles, M M

    2014-09-01

    Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment.

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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

  13. 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...

  14. Prevalence of generalized & abdominal obesity in urban & rural India- the ICMR - INDIAB Study (Phase-I) [ICMR - INDIAB-3

    PubMed Central

    Pradeepa, Rajendra; Anjana, Ranjit Mohan; Joshi, Shashank R.; Bhansali, Anil; Deepa, Mohan; Joshi, Prashant P.; Dhandania, Vinay K.; Madhu, Sri Venkata; Rao, Paturi Vishnupriya; Geetha, Loganathan; Subashini, Radhakrishnan; Unnikrishnan, Ranjit; Shukla, Deepak Kumar; Kaur, Tanvir; Mohan, Viswanathan; Das, Ashok Kumar

    2015-01-01

    Background & objectives: Overweight and obesity are rapidly increasing in countries like India. This study was aimed at determining the prevalence of generalized, abdominal and combined obesity in urban and rural India. Methods: Phase I of the ICMR-INDIAB study was conducted in a representative population of three States [Tamil Nadu (TN), Maharashtra (MH) and Jharkhand (JH)] and one Union Territory (UT)[Chandigarh (CH)] of India. A stratified multi-stage sampling design was adopted and individuals ≥20 yr of age were included. WHO Asia Pacific guidelines were used to define overweight [body mass index (BMI) ≥23 kg/m2 but <25 kg/m2), generalized obesity (GO, BMI≥25kg/m2), abdominal obesity (AO, waist circumference ≥90 cm for men and ≥80cm for women) and combined obesity (CO, GO plus AO). Of the 14,277 participants, 13,800 subjects (response rate, 96.7%) were included for the analysis (urban: n=4,063; rural: n=9737). Results: The prevalence of GO was 24.6, 16.6, 11.8 and 31.3 per cent among residents of TN, MH, JH and CH, while the prevalence of AO was 26.6, 18.7, 16.9 and 36.1 per cent, respectively. CO was present in 19.3, 13.0, 9.8 and 26.6 per cent of the TN, MH, JH and CH population. The prevalence of GO, AO and CO were significantly higher among urban residents compared to rural residents in all the four regions studied. The prevalence of overweight was 15.2, 11.3, 7.8 and 15.9 per cent among residents of TN, MH, JH and CH, respectively. Multiple logistic regression analysis showed that female gender, hypertension, diabetes, higher socio-economic status, physical inactivity and urban residence were significantly associated with GO, AO and CO in all the four regions studied. Age was significantly associated with AO and CO, but not with GO. Interpretation & conclusions: Prevalence of AO as well as of GO were high in India. Extrapolated to the whole country, 135, 153 and 107 million individuals will have GO, AO and CO, respectively. However, these figures

  15. 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 ...

  16. 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

  17. 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

  18. 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

  19. Relationships of serum soluble E-selectin concentration with insulin sensitivity and metabolic flexibility in lean and obese women.

    PubMed

    Adamska, Agnieszka; Karczewska-Kupczewska, Monika; Nikołajuk, Agnieszka; Otziomek, Elżbieta; Górska, Maria; Kowalska, Irina; Strączkowski, Marek

    2014-04-01

    The markers of endothelial dysfunction, including soluble E-selectin (sE-selectin), are related to insulin resistance, which is associated with metabolic inflexibility, i.e., impaired stimulation of carbohydrate oxidation and impaired inhibition of lipid oxidation by insulin. Endothelial dysfunction may also be important in the metabolic syndrome. The aim of our study was to analyze the association of sE-selectin with insulin sensitivity and metabolic flexibility in lean and obese women. We examined 22 lean women (BMI < 25 kg m(-2)) and 26 overweight or obese women (BMI > 25 kg m(-2)) with normal glucose tolerance. A hyperinsulinemic euglycemic clamp and indirect calorimetry were performed. An increase in the respiratory exchange ratio in response to insulin was used as a measure of metabolic flexibility. Obese women had lower insulin sensitivity (P < 0.01), higher plasma sE-selectin (P = 0.007), and higher the metabolic syndrome total Z-score (MS Z-score) (P < 0.0001). Insulin sensitivity was negatively correlated with sE-selectin level (r = -0.24, P = 0.04). sE-selectin was associated with the rate of carbohydrate oxidation at the baseline state (r = 0.31, P = 0.007) and was negatively correlated with metabolic flexibility (r = -0.34, P = 0.003). MS Z-score correlated positively with sE-selectin level and negatively with metabolic flexibility and insulin sensitivity (r = 0.49, P < 0.0001, r = -0.29, P = 0.04, r = -0.51, P < 0.0001, respectively). In multiple regression analysis we observed that the relationship between metabolic flexibility and sE-selectin (β = -0.36; P = 0.004) was independent of the other evaluated factors. Our data suggest that endothelial dysfunction as assessed by plasma sE-selectin is associated with metabolic flexibility, inversely and independently of the other estimated factors. PMID:23934358

  20. Relationships of serum soluble E-selectin concentration with insulin sensitivity and metabolic flexibility in lean and obese women.

    PubMed

    Adamska, Agnieszka; Karczewska-Kupczewska, Monika; Nikołajuk, Agnieszka; Otziomek, Elżbieta; Górska, Maria; Kowalska, Irina; Strączkowski, Marek

    2014-04-01

    The markers of endothelial dysfunction, including soluble E-selectin (sE-selectin), are related to insulin resistance, which is associated with metabolic inflexibility, i.e., impaired stimulation of carbohydrate oxidation and impaired inhibition of lipid oxidation by insulin. Endothelial dysfunction may also be important in the metabolic syndrome. The aim of our study was to analyze the association of sE-selectin with insulin sensitivity and metabolic flexibility in lean and obese women. We examined 22 lean women (BMI < 25 kg m(-2)) and 26 overweight or obese women (BMI > 25 kg m(-2)) with normal glucose tolerance. A hyperinsulinemic euglycemic clamp and indirect calorimetry were performed. An increase in the respiratory exchange ratio in response to insulin was used as a measure of metabolic flexibility. Obese women had lower insulin sensitivity (P < 0.01), higher plasma sE-selectin (P = 0.007), and higher the metabolic syndrome total Z-score (MS Z-score) (P < 0.0001). Insulin sensitivity was negatively correlated with sE-selectin level (r = -0.24, P = 0.04). sE-selectin was associated with the rate of carbohydrate oxidation at the baseline state (r = 0.31, P = 0.007) and was negatively correlated with metabolic flexibility (r = -0.34, P = 0.003). MS Z-score correlated positively with sE-selectin level and negatively with metabolic flexibility and insulin sensitivity (r = 0.49, P < 0.0001, r = -0.29, P = 0.04, r = -0.51, P < 0.0001, respectively). In multiple regression analysis we observed that the relationship between metabolic flexibility and sE-selectin (β = -0.36; P = 0.004) was independent of the other evaluated factors. Our data suggest that endothelial dysfunction as assessed by plasma sE-selectin is associated with metabolic flexibility, inversely and independently of the other estimated factors.

  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

    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. 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

  5. Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance.

    PubMed

    Lee, Byung-Cheol; Lee, Jongsoon

    2014-03-01

    There is increasing evidence showing that inflammation is an important pathogenic mediator of the development of obesity-induced insulin resistance. It is now generally accepted that tissue-resident immune cells play a major role in the regulation of this obesity-induced inflammation. The roles that adipose tissue (AT)-resident immune cells play have been particularly extensively studied. AT contains most types of immune cells and obesity increases their numbers and activation levels, particularly in AT macrophages (ATMs). Other pro-inflammatory cells found in AT include neutrophils, Th1 CD4 T cells, CD8 T cells, B cells, DCs, and mast cells. However, AT also contains anti-inflammatory cells that counter the pro-inflammatory immune cells that are responsible for the obesity-induced inflammation in this tissue. These anti-inflammatory cells include regulatory CD4 T cells (Tregs), Th2 CD4 T cells, and eosinophils. Hence, AT inflammation is shaped by the regulation of pro- and anti-inflammatory immune cell homeostasis, and obesity skews this balance towards a more pro-inflammatory status. Recent genetic studies revealed several molecules that participate in the development of obesity-induced inflammation and insulin resistance. In this review, the cellular and molecular players that participate in the regulation of obesity-induced inflammation and insulin resistance are discussed, with particular attention being placed on the roles of the cellular players in these pathogeneses. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

  6. MsrA Overexpression Targeted to the Mitochondria, but Not Cytosol, Preserves Insulin Sensitivity in Diet-Induced Obese Mice.

    PubMed

    Hunnicut, JennaLynn; Liu, Yuhong; Richardson, Arlan; Salmon, Adam B

    2015-01-01

    There is growing evidence that oxidative stress plays an integral role in the processes by which obesity causes type 2 diabetes. We previously identified that mice lacking the protein oxidation repair enzyme methionine sulfoxide reductase A (MsrA) are particularly prone to obesity-induced insulin resistance suggesting an unrecognized role for this protein in metabolic regulation. The goals of this study were to test whether increasing the expression of MsrA in mice can protect against obesity-induced metabolic dysfunction and to elucidate the potential underlying mechanisms. Mice with increased levels of MsrA in the mitochondria (TgMito MsrA) or in the cytosol (TgCyto MsrA) were fed a high fat/high sugar diet and parameters of glucose homeostasis were monitored. Mitochondrial content, markers of mitochondrial proteostasis and mitochondrial energy utilization were assessed. TgMito MsrA, but not TgCyto MsrA, mice remain insulin sensitive after high fat feeding, though these mice are not protected from obesity. This metabolically healthy obese phenotype of TgMito MsrA mice is not associated with changes in mitochondrial number or biogenesis or with a reduction of proteostatic stress in the mitochondria. However, our data suggest that increased mitochondrial MsrA can alter metabolic homeostasis under diet-induced obesity by activating AMPK signaling, thereby defining a potential mechanism by which this genetic alteration can prevent insulin resistance without affecting obesity. Our data suggest that identification of targets that maintain and regulate the integrity of the mitochondrial proteome, particular against oxidative damage, may play essential roles in the protection against metabolic disease.

  7. MsrA Overexpression Targeted to the Mitochondria, but Not Cytosol, Preserves Insulin Sensitivity in Diet-Induced Obese Mice

    PubMed Central

    Hunnicut, JennaLynn; Liu, Yuhong; Richardson, Arlan; Salmon, Adam B.

    2015-01-01

    There is growing evidence that oxidative stress plays an integral role in the processes by which obesity causes type 2 diabetes. We previously identified that mice lacking the protein oxidation repair enzyme methionine sulfoxide reductase A (MsrA) are particularly prone to obesity-induced insulin resistance suggesting an unrecognized role for this protein in metabolic regulation. The goals of this study were to test whether increasing the expression of MsrA in mice can protect against obesity-induced metabolic dysfunction and to elucidate the potential underlying mechanisms. Mice with increased levels of MsrA in the mitochondria (TgMito MsrA) or in the cytosol (TgCyto MsrA) were fed a high fat/high sugar diet and parameters of glucose homeostasis were monitored. Mitochondrial content, markers of mitochondrial proteostasis and mitochondrial energy utilization were assessed. TgMito MsrA, but not TgCyto MsrA, mice remain insulin sensitive after high fat feeding, though these mice are not protected from obesity. This metabolically healthy obese phenotype of TgMito MsrA mice is not associated with changes in mitochondrial number or biogenesis or with a reduction of proteostatic stress in the mitochondria. However, our data suggest that increased mitochondrial MsrA can alter metabolic homeostasis under diet-induced obesity by activating AMPK signaling, thereby defining a potential mechanism by which this genetic alteration can prevent insulin resistance without affecting obesity. Our data suggest that identification of targets that maintain and regulate the integrity of the mitochondrial proteome, particular against oxidative damage, may play essential roles in the protection against metabolic disease. PMID:26448611

  8. 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.

  9. Insulin

    MedlinePlus

    ... pump is connected to your body by a flexible tube that has a tip that sticks under your skin. A cartridge of insulin is put in the pump. The insulin flows through the tube into your body. The pump controls how much insulin goes into your body. The ...

  10. 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

  11. 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

  12. Insulin Resistance and Obesity Affect Lipid Profile in the Salivary Glands.

    PubMed

    Matczuk, Jan; Zalewska, Anna; Łukaszuk, Bartłomiej; Knaś, Małgorzata; Maciejczyk, Mateusz; Garbowska, Marta; Ziembicka, Dominika M; Waszkiel, Danuta; Chabowski, Adrian; Żendzian-Piotrowska, Małgorzata; Kurek, Krzysztof

    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

  13. Abdominal obesity is strongly associated with Cardiovascular Disease and its Risk Factors in Elderly and very Elderly Community-dwelling Chinese

    PubMed Central

    Fan, Huimin; Li, Xiaolin; Zheng, Liang; Chen, Xiaoli; lan, Qin; Wu, Hong; Ding, Xugang; Qian, Dingguang; Shen, Yixin; Yu, Zuoren; Fan, Lieying; Chen, Ming; Tomlinson, Brian; Chan, Paul; Zhang, Yuzhen; Liu, Zhongmin

    2016-01-01

    Obesity is usually considered to predispose to atherosclerotic cardiovascular disease (ASCVD) but milder degrees of obesity or overweight may be protective in some elderly populations. We examined the relationships between general and abdominal obesity indices with ASCVD and its risk factors in elderly (aged ≥65 years) Shanghai community residents Among the 3950 participants, 21.5% had ASCVD, 56.2% had body mass index (BMI) ≥24 kg/m2, 50.1% had high waist circumference (WC) and 77.1% had waist-to-height ratio (WHtR) ≥0.50. WHtR increased with age in both men and women whereas WC increased with age only in women and BMI decreased with age only in men. The optimal WHtR cut-off value to predict the risk of ASCVD determined by receiver operating characteristic analysis was WHtR ≥0.53 with a prevalence of 55.8%. Having abdominal obesity was significantly associated with prevalent ASCVD with WHtR ≥0.53 having a higher value for the odds ratio than high WC, whereas high BMI was not associated. All three indices predicted high glucose, triglycerides and hsCRP levels but only the WHtR ≥0.53 showed a significant association with physical activity. Abdominal obesity indices, but not BMI, predicted prevalent ASCVD and its risk factors in this elderly Chinese population. PMID:26882876

  14. Effects of concurrent training on oxidative stress and insulin resistance in obese individuals.

    PubMed

    Medeiros, Niara da Silva; de Abreu, Fabiana Guichard; Colato, Alana Schraiber; de Lemos, Leandro Silva; Ramis, Thiago Rozales; Dorneles, Gilson Pires; Funchal, Cláudia; Dani, Caroline

    2015-01-01

    Obesity is associated with insulin resistance (IR) and increased oxidative stress. Thus, the present study aimed to evaluate anthropometric parameters, IR, and oxidative stress in obese individuals subjected to two types of concurrent training at the same intensity but differing in frequency. Accordingly, 25 individuals were divided into two groups: concurrent training 1 (CT1) (5 d/wk) and concurrent training 2 (CT2) (3 d/wk), both with moderate intensity. Anthropometric parameters, IR, and oxidative stress were analyzed before and after 26 sessions of training. Both groups had reduced body weight and body mass index (P < 0.05), but only CT1 showed lower body fat percentage and increased basal metabolic rate (P < 0.05). Moreover, CT1 had increased HOMA-IR and decreased protein damage (carbonyl level), and CT2 had decreased HOMA-IR and increased lipid peroxidation (TBARS level) (P < 0.05). On the other hand, both training protocols reduced the GPx activity. It can be concluded that both types of concurrent training could be an alternative for lowering body weight and BMI. Also, it was observed that concurrent training, depending on the frequency, can contribute to reducing body fat, oxidative damage (protein oxidation), and IR but can induce oxidative damage to lipids. More studies are needed to elucidate the mechanisms involved. PMID:25722796

  15. 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

  16. 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. PMID:26280128

  17. Small Molecule Kaempferol Promotes Insulin Sensitivity and Preserved Pancreatic β-Cell Mass in Middle-Aged Obese Diabetic Mice

    PubMed Central

    Alkhalidy, Hana; Moore, William; Zhang, Yanling; Wang, Aihua; Ali, Mostafa; Suh, Kyung-Shin; Zhen, Wei; Cheng, Zhiyong; Jia, Zhenquan; Hulver, Matthew

    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. PMID:26064984

  18. 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

  19. Curcumin rescues high fat diet-induced obesity and insulin sensitivity in mice through regulating SREBP pathway.

    PubMed

    Ding, Lili; Li, Jinmei; Song, Baoliang; Xiao, Xu; Zhang, Binfeng; Qi, Meng; Huang, Wendong; Yang, Li; Wang, Zhengtao

    2016-08-01

    Obesity and its major co-morbidity, type 2 diabetes, have reached an alarming epidemic prevalence without an effective treatment available. It has been demonstrated that inhibition of SREBP pathway may be a useful strategy to treat obesity with type 2 diabetes. Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. In current study, we identified a small molecule, curcumin, inhibited the SREBP expression in vitro. The inhibition of SREBP by curcumin decreased the biosynthesis of cholesterol and fatty acid. In vivo, curcumin ameliorated HFD-induced body weight gain and fat accumulation in liver or adipose tissues, and improved serum lipid levels and insulin sensitivity in HFD-induced obese mice. Consistently, curcumin regulates SREBPs target genes and metabolism associated genes in liver or adipose tissues, which may directly contribute to the lower lipid level and improvement of insulin resistance. Take together, curcumin, a major active component of Curcuma longa could be a potential leading compound for development of drugs for the prevention of obesity and insulin resistance. PMID:27208389

  20. Coffee intake mitigated inflammation and obesity-induced insulin resistance in skeletal muscle of high-fat diet-induced obese mice.

    PubMed

    Jia, Huijuan; Aw, Wanping; Egashira, Kenji; Takahashi, Shoko; Aoyama, Shinya; Saito, Kenji; Kishimoto, Yoshimi; Kato, Hisanori

    2014-05-01

    Epidemiologic findings offer the promise that coffee or its many constituents may be useful as a dietary intervention in type 2 diabetes (T2D) prevention. We aimed to elucidate the molecular mechanisms involved in the ameliorative effects of caffeinated coffee (CC), decaffeinated coffee (DC) and unroasted caffeinated green coffee (GC) on skeletal muscle gene expression profiles and their relationships in an obesity animal model. Eight-week-old male C57BL6 mice were raised for 9 weeks ad libitum on a normal diet, a high-fat diet, or high-fat diet containing 2 % freeze-dried CC, or DC, or GC. Total RNA and protein were extracted from skeletal muscle and subjected to microarray (Mouse Genome 430 2.0, Affymetrix) and western blotting analyses, respectively. Coffee intake mitigated the insulin resistance by decreasing plasma glucose levels during an insulin tolerance test and by increasing tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), p85/IRS-1 complex and pAkt/PKB (protein kinase B). In addition, coffee intake down-regulated the anti-inflammatory genes activating transcription factor 3, FBJ osteosarcoma oncogene, heat shock protein 1A, heat shock protein 1B and synuclein, gamma and the inflammation-associated insulin signaling genes stearoyl-coenzyme A desaturase 1 and secreted phosphoprotein 1. These results provide scientific insight on the probable positive effects of coffee intake on impaired insulin signaling, inflammation and obesity, thereby providing a new perspective on the prevention of obesity and T2D.

  1. Coffee intake mitigated inflammation and obesity-induced insulin resistance in skeletal muscle of high-fat diet-induced obese mice.

    PubMed

    Jia, Huijuan; Aw, Wanping; Egashira, Kenji; Takahashi, Shoko; Aoyama, Shinya; Saito, Kenji; Kishimoto, Yoshimi; Kato, Hisanori

    2014-05-01

    Epidemiologic findings offer the promise that coffee or its many constituents may be useful as a dietary intervention in type 2 diabetes (T2D) prevention. We aimed to elucidate the molecular mechanisms involved in the ameliorative effects of caffeinated coffee (CC), decaffeinated coffee (DC) and unroasted caffeinated green coffee (GC) on skeletal muscle gene expression profiles and their relationships in an obesity animal model. Eight-week-old male C57BL6 mice were raised for 9 weeks ad libitum on a normal diet, a high-fat diet, or high-fat diet containing 2 % freeze-dried CC, or DC, or GC. Total RNA and protein were extracted from skeletal muscle and subjected to microarray (Mouse Genome 430 2.0, Affymetrix) and western blotting analyses, respectively. Coffee intake mitigated the insulin resistance by decreasing plasma glucose levels during an insulin tolerance test and by increasing tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), p85/IRS-1 complex and pAkt/PKB (protein kinase B). In addition, coffee intake down-regulated the anti-inflammatory genes activating transcription factor 3, FBJ osteosarcoma oncogene, heat shock protein 1A, heat shock protein 1B and synuclein, gamma and the inflammation-associated insulin signaling genes stearoyl-coenzyme A desaturase 1 and secreted phosphoprotein 1. These results provide scientific insight on the probable positive effects of coffee intake on impaired insulin signaling, inflammation and obesity, thereby providing a new perspective on the prevention of obesity and T2D. PMID:24599575

  2. Importance of Lean Muscle Maintenance to Improve Insulin Resistance by Body Weight Reduction in Female Patients with Obesity

    PubMed Central

    Kurose, Satoshi; Shinno, Hiromi; Cao Thu, Ha; Takao, Nana; Tsutsumi, Hiromi; Kimura, Yutaka

    2016-01-01

    Background It has recently been suggested that skeletal muscle has an important role in insulin resistance in obesity, in addition to exercise tolerance and the fat index. The aim of this study was to identify body composition factors that contribute to improvement of insulin resistance in female patients with obesity who reduce body weight. Methods We studied 92 female obese patients (age 40.9±10.4 years, body mass index 33.2±4.6 kg/m2) who reduced body weight by ≥5% after an intervention program including diet, exercise therapy, and cognitive behavioral therapy. Before and after the intervention, body composition was evaluated by dual-energy X-ray absorptiometry to examine changes in skeletal muscle mass. Homeostasis model assessment of insulin resistance (HOMA-IR) was measured as an index of insulin resistance. Cardiopulmonary exercise was also performed by all patients. Results There were significant improvements in body weight (–10.3%±4.5%), exercise tolerance (anaerobic threshold oxygen uptake 9.1%±18.4%, peak oxygen uptake 11.0%±14.2%), and HOMA-IR (–20.2%±38.3%). Regarding body composition, there were significant decreases in total body fat (–19.3%±9.6%), total fat-free mass (–2.7%±4.3%), and % body fat (–10.1%±7.5%), whereas % skeletal muscle significantly increased (8.9%±7.2%). In stepwise multiple linear regression analysis with change in HOMA-IR as the dependent variable, the change in % skeletal muscle was identified as an independent predictor (β=–0.280, R2=0.068, P<0.01). Conclusion Improvement of insulin resistance in female obese patients requires maintenance of skeletal muscle mass. PMID:27126885

  3. 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.

  4. CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of macrophage polarization in adipose tissues.

    PubMed

    Fujii, Masakazu; Inoguchi, Toyoshi; Batchuluun, Battsetseg; Sugiyama, Naonobu; Kobayashi, Kunihisa; Sonoda, Noriyuki; Takayanagi, Ryoichi

    2013-08-16

    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.

  5. Adult-Onset Obesity Reveals Prenatal Programming of Glucose-Insulin Sensitivity in Male Sheep Nutrient Restricted during Late Gestation

    PubMed Central

    Rhodes, Philip; Craigon, Jim; Gray, Clint; Rhind, Stuart M.; Loughna, Paul T.; Gardner, David S.

    2009-01-01

    Background Obesity invokes a range of metabolic disturbances, but the transition from a poor to excessive nutritional environment may exacerbate adult metabolic dysfunction. The current study investigated global maternal nutrient restriction during early or late gestation on glucose tolerance and insulin sensitivity in the adult offspring when lean and obese. Methods/Principal Findings Pregnant sheep received adequate (1.0M; CE, n = 6) or energy restricted (0.7M) diet during early (1–65 days; LEE, n = 6) or late (65–128 days; LEL, n = 7) gestation (term ∼147 days). Subsequent offspring remained on pasture until 1.5 years when all received glucose and insulin tolerance tests (GTT & ITT) and body composition determination by dual energy x-ray absorptiometry (DXA). All animals were then exposed to an obesogenic environment for 6–7 months and all protocols repeated. Prenatal dietary treatment had no effect on birth weight or on metabolic endpoints when animals were ‘lean’ (1.5 years). Obesity revealed generalised metabolic ‘inflexibility’ and insulin resistance; characterised by blunted excursions of plasma NEFA and increased insulinAUC (from 133 to 341 [s.e.d. 26] ng.ml−1.120 mins) during a GTT, respectively. For LEL vs. CE, the peak in plasma insulin when obese was greater (7.8 vs. 4.7 [s.e.d. 1.1] ng.ml−1) and was exacerbated by offspring sex (i.e. 9.8 vs. 4.4 [s.e.d. 1.16] ng.ml−1; LEL male vs. CE male, respectively). Acquisition of obesity also significantly influenced the plasma lipid and protein profile to suggest, overall, greater net lipogenesis and reduced protein metabolism. Conclusions This study indicates generalised metabolic dysfunction with adult-onset obesity which also exacerbates and ‘reveals’ programming of glucose-insulin sensitivity in male offspring prenatally exposed to maternal undernutrition during late gestation. Taken together, the data suggest that metabolic function appears little compromised in young

  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. 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

  8. HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats.

    PubMed

    Miranda, Rosiane A; Torrezan, Rosana; de Oliveira, Júlio C; Barella, Luiz F; da Silva Franco, Claudinéia C; Lisboa, Patrícia C; Moura, Egberto G; Mathias, Paulo C F

    2016-07-01

    Neuroendocrine dysfunctions such as the hyperactivity of the vagus nerve and hypothalamus-pituitary-adrenal (HPA) axis greatly contribute to obesity and hyperinsulinemia; however, little is known about these dysfunctions in the pancreatic β-cells of obese individuals. We used a hypothalamic-obesity model obtained by neonatal treatment with monosodium l-glutamate (MSG) to induce obesity. To assess the role of the HPA axis and vagal tonus in the genesis of hypercorticosteronemia and hyperinsulinemia in an adult MSG-obese rat model, bilateral adrenalectomy (ADX) and subdiaphragmatic vagotomy (VAG) alone or combined surgeries (ADX-VAG) were performed. To study glucose-induced insulin secretion (GIIS) and the cholinergic insulinotropic process, pancreatic islets were incubated with different glucose concentrations with or without oxotremorine-M, a selective agonist of the M3 muscarinic acetylcholine receptor (M3AChR) subtype. Protein expression of M3AChR in pancreatic islets, corticosteronemia, and vagus nerve activity was also evaluated. Surgeries reduced 80% of the body weight gain. Fasting glucose and insulin were reduced both by ADX and ADX-VAG, whereas VAG was only associated with hyperglycemia. The serum insulin post-glucose stimulation was lower in all animals that underwent an operation. Vagal activity was decreased by 50% in ADX rats. In the highest glucose concentration, both surgeries reduced GIIS by 50%, whereas ADX-VAG decreased by 70%. Additionally, M3AChR activity was recovered by the individual surgeries. M3AChR protein expression was reduced by ADX. Both the adrenal gland and vagus nerve contribute to the hyperinsulinemia in the MSG model, although adrenal is more crucial as it appears to modulate parasympathetic activity and M3AChR expression in obesity.

  9. Plasminogen activator inhibitor-1 deficiency ameliorates insulin resistance and hyperlipidemia but not bone loss in obese female mice.

    PubMed

    Tamura, Yukinori; Kawao, Naoyuki; Yano, Masato; Okada, Kiyotaka; Matsuo, Osamu; Kaji, Hiroshi

    2014-05-01

    We previously demonstrated that plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis, is involved in type 1 diabetic bone loss in female mice. PAI-1 is well known as an adipogenic factor induced by obesity. We therefore examined the effects of PAI-1 deficiency on bone and glucose and lipid metabolism in high-fat and high-sucrose diet (HF/HSD)-induced obese female mice. Female wild-type (WT) and PAI-1-deficient mice were fed with HF/HSD or normal diet for 20 weeks from 10 weeks of age. HF/HSD increased the levels of plasma PAI-1 in WT mice. PAI-1 deficiency suppressed the levels of blood glucose, plasma insulin, and total cholesterol elevated by obesity. Moreover, PAI-1 deficiency improved glucose intolerance and insulin resistance induced by obesity. Bone mineral density (BMD) at trabecular bone as well as the levels of osterix, alkaline phosphatase, and receptor activator of nuclear factor κB ligand mRNA in tibia were decreased by HF/HSD in WT mice, and those changes by HF/HSD were not affected by PAI-1 deficiency. HF/HSD increased the levels of plasma TNF-α in both WT and PAI-1-deficient mice, and the levels of plasma TNF-α were negatively correlated with trabecular BMD in tibia of female mice. In conclusion, we revealed that PAI-1 deficiency does not affect the trabecular bone loss induced by obesity despite the amelioration of insulin resistance and hyperlipidemia in female mice. Our data suggest that the changes of BMD and bone metabolism by obesity might be independent of PAI-1 as well as glucose and lipid metabolism.

  10. Obesity and Its Metabolic Complications: The Role of Adipokines and the Relationship between Obesity, Inflammation, Insulin Resistance, Dyslipidemia and Nonalcoholic Fatty Liver Disease

    PubMed Central

    Jung, Un Ju; Choi, Myung-Sook

    2014-01-01

    Accumulating evidence indicates that obesity is closely associated with an increased risk of metabolic diseases such as insulin resistance, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease. Obesity results from an imbalance between food intake and energy expenditure, which leads to an excessive accumulation of adipose tissue. Adipose tissue is now recognized not only as a main site of storage of excess energy derived from food intake but also as an endocrine organ. The expansion of adipose tissue produces a number of bioactive substances, known as adipocytokines or adipokines, which trigger chronic low-grade inflammation and interact with a range of processes in many different organs. Although the precise mechanisms are still unclear, dysregulated production or secretion of these adipokines caused by excess adipose tissue and adipose tissue dysfunction can contribute to the development of obesity-related metabolic diseases. In this review, we focus on the role of several adipokines associated with obesity and the potential impact on obesity-related metabolic diseases. Multiple lines evidence provides valuable insights into the roles of adipokines in the development of obesity and its metabolic complications. Further research is still required to fully understand the mechanisms underlying the metabolic actions of a few newly identified adipokines. PMID:24733068

  11. 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. PMID:23520556

  12. 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

  13. The Roles of Adipokines, Proinflammatory Cytokines, and Adipose Tissue Macrophages in Obesity-Associated Insulin Resistance in Modest Obesity and Early Metabolic Dysfunction.

    PubMed

    Kang, Yea Eun; 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

  14. 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

  15. 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.

  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. 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

  18. Evaluation of Usefulness of Serum Insulin as Sensitive Predictor of Cardiovascular Dysfunction in Obese Individuals with Normal Lipid Profile

    PubMed Central

    Bavikar, Jayashree S.; Asegaonkar, Shilpa B.; Bardapurkar, Jayashree S.; Domple, Vijay; Rai, Pooja SK; Pawar, Smita

    2014-01-01

    Background: Prevalence of obesity and its subsequent cardiometabolic complications is on exponential rise. Hyperinsulinemia develops in obese individuals long before other metabolic derangements of obesity take place and may be a common pathophysiological factor tying together various components of cardiometabolic dysfunction. Aim: Present study was aimed at evaluating the role of insulin as a sensitive and independent cardiovascular risk marker in apparently healthy overweight and obese individuals with normal lipid profile. Settings and design: This was an opd based case Control study including 100 overweight and obese individuals with normal lipid profile & 100 age and sex matched normal weight healthy controls. Materials and Methods: Participants were evaluated based on detailed history, clinical examination and laboratory investigations. Blood samples were collected after overnight fast. Serum insulin was estimated by chemiluminescence method, glucose and lipid profile (CHOLESTEROL, HDL, TG, LDL) by chemical assays on a fully automated analyser system. Statistical analysis: Results were analyzed by unpaired t-test, p-value was determined & Correlation coefficient was calculated amongst various parameters. Results: Significant difference was noted in mean values of BMI (29.69±1.28 VS 23.47±1.09), waist / hip ratio (0.91±0.07 VS 0.79±0.05) and serum insulin (10.54±2.5 VS 5.94±1.53) (p<0.01) in cases as compared to controls respectively. Glucose levels were high in cases (89.58±8.0 mg/dl) as compared to controls (88.8±7.56 mg/dl) but the difference was statistically insignificant (p=0.11). Hyperinsulinemia was observed in 41 cases & 4 controls. Serum insulin highly correlated with Waist/ hip ratio (R=0.53) than BMI (R=0.26). Conclusion: Study suggests Insulin; a simple, sensitive & independent cardiovascular risk predictor in obesity even with normal lipid profile with a potential to reveal hidden burden of metabolic dysfunction and offers a hope that

  19. Longitudinal Study of Depressive Symptoms and Progression of Insulin Resistance in Youth at Risk for Adult Obesity

    PubMed Central

    Shomaker, Lauren B.; Tanofsky-Kraff, Marian; Stern, Elizabeth A.; Miller, Rachel; Zocca, Jaclyn M.; Field, Sara E.; Yanovski, Susan Z.; Hubbard, Van S.; Yanovski, Jack A.

    2011-01-01

    OBJECTIVE The purpose of this study was to determine whether having childhood depressive symptoms is a risk factor that prospectively predicts impairment in glucose homeostasis. RESEARCH DESIGN AND METHODS A non–treatment-seeking sample of 115 children (aged 5–13 years), oversampled for being at risk for adult obesity, was assessed at baseline and again ~6 years later. Children self-reported depressive symptoms using the Children’s Depression Inventory at baseline. Insulin resistance was assessed at baseline and follow-up with the homeostasis model assessment of insulin resistance index (HOMA-IR). RESULTS Children’s depressive symptoms were a significant predictor of follow-up HOMA-IR, fasting insulin, and fasting glucose in models accounting for baseline HOMA-IR, insulin, or glucose values; sex; race; baseline age; baseline BMI; change in BMI at follow-up; family history of type 2 diabetes; and time in the study (P < 0.01). CONCLUSIONS In this study, depressive symptomatology at baseline predicted the progression of insulin resistance during child and adolescent development independent of changes in BMI. Research is needed to determine whether early intervention to decrease elevated depressive symptoms in youth ameliorates later development of insulin resistance and lessens the risk of type 2 diabetes. PMID:21911779

  20. Longitudinal study of depressive symptoms and progression of insulin resistance in youth at risk for adult obesity.

    PubMed

    Shomaker, Lauren B; Tanofsky-Kraff, Marian; Stern, Elizabeth A; Miller, Rachel; Zocca, Jaclyn M; Field, Sara E; Yanovski, Susan Z; Hubbard, Van S; Yanovski, Jack A

    2011-11-01

    OBJECTIVE The purpose of this study was to determine whether having childhood depressive symptoms is a risk factor that prospectively predicts impairment in glucose homeostasis. RESEARCH DESIGN AND METHODS A non-treatment-seeking sample of 115 children (aged 5-13 years), oversampled for being at risk for adult obesity, was assessed at baseline and again ~6 years later. Children self-reported depressive symptoms using the Children's Depression Inventory at baseline. Insulin resistance was assessed at baseline and follow-up with the homeostasis model assessment of insulin resistance index (HOMA-IR). RESULTS Children's depressive symptoms were a significant predictor of follow-up HOMA-IR, fasting insulin, and fasting glucose in models accounting for baseline HOMA-IR, insulin, or glucose values; sex; race; baseline age; baseline BMI; change in BMI at follow-up; family history of type 2 diabetes; and time in the study (P < 0.01). CONCLUSIONS In this study, depressive symptomatology at baseline predicted the progression of insulin resistance during child and adolescent development independent of changes in BMI. Research is needed to determine whether early intervention to decrease elevated depressive symptoms in youth ameliorates later development of insulin resistance and lessens the risk of type 2 diabetes. PMID:21911779

  1. Association of gene polymorphism of the fat-mass and obesity-associated gene with insulin resistance in Japanese.

    PubMed

    Shimaoka, Izumi; Kamide, Kei; Ohishi, Mitsuru; Katsuya, Tomohiro; Akasaka, Hiroshi; Saitoh, Shigeyuki; Sugimoto, Ken; Oguro, Ryousuke; Congrains, Ada; Fujisawa, Tomomi; Shimamoto, Kazuaki; Ogihara, Toshio; Rakugi, Hiromi

    2010-03-01

    It was reported that gene polymorphisms in the fat-mass and obesity-associated gene (FTO) were associated with obesity and diabetes in several genome-wide association studies. A recent report indicated that FTO-knockout mice exhibited phenotypes of skinny body shape and normal metabolic profiles. Thus, FTO could be important in metabolic disorders. The aim of this study was to clarify the role of single nucleotide polymorphisms (SNPs) in FTO in metabolic disorders such as hypertension, obesity, diabetes, dyslipidemia, insulin resistance and metabolic syndrome in the Japanese general population using data from a cohort study in Hokkaido, namely the Tanno-Sobetsu study. Written informed consent for the genetic analysis was obtained from each subject participating in the study. A total of 1514 subjects were genotyped by TaqMan PCR methods for three SNPs, rs9939609, rs1121980 and rs1558902, in FTO. Association analyses between the SNPs and metabolic parameters were performed. Although two SNPs, rs9939609 and rs1558902, were not significantly associated with hypertension, obesity, metabolic syndrome or any metabolic parameters, additive and recessive models of rs1121980 were strongly associated with plasma immunoreactive insulin (IRI) level and homeostasis model assessment insulin resistance (HOMA-IR), even after adjusting for confounding factors such as age, gender and body mass index. A haplotype of three SNPs was also significantly associated with IRI and HOMA-IR. One SNP, rs1121980, and a haplotype of three SNPs in FTO that contains this SNP, might be important in the progression of insulin resistance in Japanese subjects.

  2. Hepatic adenylate cyclase 3 is upregulated by Liraglutide and subsequently plays a protective role in insulin resistance and obesity

    PubMed Central

    Liang, Y; Li, Z; Liang, S; Li, Y; Yang, L; Lu, M; Gu, H F; Xia, N

    2016-01-01

    Objective: Recent studies have demonstrated that adenylate cyclase 3 (AC3) has a protective role in obesity. This gene resides at the pathway with glucagon-like peptide (GLP)-1. Liraglutide is a GLP-1 analog and has independent glucose and body weight (BW)-reducing effects. In the present study, we aimed to examine whether hepatic AC3 activity was regulated by Liraglutide and to further understand the effect of AC3 in reduction of BW and insulin resistance. Subjects: The diabesity and obese mice were induced from db/db and C57BL/6 J mice, respectively, by high-fat diet. Liraglutide (0.1 mg kg−1 per 12 h) was given to the mice twice daily for 12 weeks. C57BL/6 J mice fed with chow diet and obese or diabesity mice treated with saline were used as the controls. Hepatic AC3 gene expression at mRNA and protein levels was analyzed with real-time reverse transcription-PCR and western blot. Fasting blood glucose and serum insulin levels were measured and followed insulin resistance index (HOMA-IR) was evaluated according to the homeostasis model assessment. Results: After administration of Liraglutide, BW and HOMA-IR in obese and diabesity mice were decreased, whereas hepatic AC3 mRNA and protein expression levels were upregulated. The AC3 gene expression was negatively correlated with BW, HOMA-IR and the area ratio of hepatic fat deposition in the liver. Conclusions: The present study thus provides the evidence that hepatic AC3 gene expression is upregulated by Liraglutide. The reduction of BW and improvement of insulin resistance with Liraglutide may be partially explained by AC3 activation. PMID:26807509

  3. CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages

    PubMed Central

    Zheng, Chunxing; Yang, Qian; Xu, Chunliang; Cao, Jianchang; Jiang, Menghui; Chen, Qing; Cao, Gang; Han, Yanyan; Li, Fengying; Cao, Wei; Zhang, Liying; Zhang, Li; Shi, Yufang; Wang, Ying

    2015-01-01

    Obesity-associated inflammation is accompanied by the accumulation of adipose tissue macrophages (ATMs), which is believed to predispose obese individuals to insulin resistance. CD11b (integrin αM) is highly expressed on monocytes and macrophages and is critical for their migration and function. We found here that high-fat diet–induced insulin resistance was significantly reduced in CD11b-deficient mice. Interestingly, the recruitment of monocytes to adipose tissue is impaired when CD11b is deficient, although the cellularity of ATMs in CD11b-deficient mice is higher than that in wild-type mice. We further found that the increase in ATMs is caused mainly by their vigorous proliferation in the absence of CD11b. Moreover, the proliferation and alternative activation of ATMs are regulated by the IL-4/STAT6 axis, which is inhibited by CD11b through the activity of phosphatase SHP-1. Thus, CD11b plays a critical role in obesity-induced insulin resistance by limiting the proliferation and alternative activation of ATMs. PMID:26669445

  4. Imbalance between Neutrophil Elastase and its Inhibitor α1-Antitrypsin in Obesity Alters Insulin Sensitivity, Inflammation, and Energy Expenditure

    PubMed Central

    Mansuy-Aubert, Virginie; Zhou, Qiong L.; Xie, Xiangyang; Gong, Zhenwei; Huang, Jun-Yuan; Khan, Abdul R.; Aubert, Gregory; Candelaria, Karla; Thomas, Shantele; Shin, Dong-Ju; Booth, Sarah; Baig, Shahid M.; Bilal, Ahmed; Hwang, Daehee; Zhang, Hui; Lovell-Badge, Robin; Smith, Steven R.; Awan, Fazli R.; Jiang, Zhen Y.

    2013-01-01

    SUMMARY The molecular mechanisms involved in the development of obesity and related complications remain unclear. Here, we report that obese mice and human subjects have increased activity of neutrophil elastase (NE) and decreased serum levels of the NE inhibitor, α1-antitrypsin (A1AT, SerpinA1). NE null (Ela2−/−) mice and A1AT transgenic mice were resistant to high-fat diet (HFD)-induced bodyweight gain, insulin resistance, inflammation and fatty liver. NE inhibitor GW311616A reversed insulin resistance and bodyweight gain in HFD-fed mice. Compared with wild-type mice, Ela2−/− mice augmented circulating high molecular weight (HMW) adiponectin levels, phosphorylation of AMP-activated protein kinase (AMPK) and fatty acid oxidation (FAO) in the liver and brown adipose tissue (BAT), and uncoupling protein (UCP1) levels in the BAT. These data suggest that the A1AT-NE system regulates AMPK signaling, FAO and energy expenditure. The imbalance between A1AT and NE contributes to the development of obesity and related inflammation, insulin resistance and liver steatosis. PMID:23562077

  5. White Pitaya (Hylocereus undatus) Juice Attenuates Insulin Resistance and Hepatic Steatosis in Diet-Induced Obese Mice

    PubMed Central

    Song, Haizhao; Zheng, Zihuan; Wu, Jianan; Lai, Jia; Chu, Qiang; Zheng, Xiaodong

    2016-01-01

    Insulin resistance and hepatic steatosis are the most common complications of obesity. Pitaya is an important source of phytochemicals such as polyphenols, flavonoid and vitamin C which are related to its antioxidant activity. The present study was conducted to evaluate the influence of white pitaya juice (WPJ) on obesity-related metabolic disorders (e.g. insulin resistance and hepatic steatosis) in high-fat diet-fed mice. Forty-eight male C57BL/6J mice were assigned into four groups and fed low-fat diet with free access to water or WPJ, or fed high-fat diet with free access to water or WPJ for 14 weeks. Our results showed that administration of WPJ improved high-fat diet-induced insulin resistance, hepatic steatosis and adipose hypertrophy, but it exerted no influence on body weight gain in mice. Hepatic gene expression analysis indicated that WPJ supplement not only changed the expression profile of genes involved in lipid and cholesterol metabolism (Srebp1, HMGCoR, Cpt1b, HL, Insig1 and Insig2) but also significantly increased the expression levels of FGF21-related genes (Klb, FGFR2, Egr1 and cFos). In conclusion, WPJ protected from diet-induced hepatic steatosis and insulin resistance, which was associated with the improved FGF21 resistance and lipid metabolism. PMID:26914024

  6. White Pitaya (Hylocereus undatus) Juice Attenuates Insulin Resistance and Hepatic Steatosis in Diet-Induced Obese Mice.

    PubMed

    Song, Haizhao; Zheng, Zihuan; Wu, Jianan; Lai, Jia; Chu, Qiang; Zheng, Xiaodong

    2016-01-01

    Insulin resistance and hepatic steatosis are the most common complications of obesity. Pitaya is an important source of phytochemicals such as polyphenols, flavonoid and vitamin C which are related to its antioxidant activity. The present study was conducted to evaluate the influence of white pitaya juice (WPJ) on obesity-related metabolic disorders (e.g. insulin resistance and hepatic steatosis) in high-fat diet-fed mice. Forty-eight male C57BL/6J mice were assigned into four groups and fed low-fat diet with free access to water or WPJ, or fed high-fat diet with free access to water or WPJ for 14 weeks. Our results showed that administration of WPJ improved high-fat diet-induced insulin resistance, hepatic steatosis and adipose hypertrophy, but it exerted no influence on body weight gain in mice. Hepatic gene expression analysis indicated that WPJ supplement not only changed the expression profile of genes involved in lipid and cholesterol metabolism (Srebp1, HMGCoR, Cpt1b, HL, Insig1 and Insig2) but also significantly increased the expression levels of FGF21-related genes (Klb, FGFR2, Egr1 and cFos). In conclusion, WPJ protected from diet-induced hepatic steatosis and insulin resistance, which was associated with the improved FGF21 resistance and lipid metabolism. PMID:26914024

  7. White Pitaya (Hylocereus undatus) Juice Attenuates Insulin Resistance and Hepatic Steatosis in Diet-Induced Obese Mice.

    PubMed

    Song, Haizhao; Zheng, Zihuan; Wu, Jianan; Lai, Jia; Chu, Qiang; Zheng, Xiaodong

    2016-01-01

    Insulin resistance and hepatic steatosis are the most common complications of obesity. Pitaya is an important source of phytochemicals such as polyphenols, flavonoid and vitamin C which are related to its antioxidant activity. The present study was conducted to evaluate the influence of white pitaya juice (WPJ) on obesity-related metabolic disorders (e.g. insulin resistance and hepatic steatosis) in high-fat diet-fed mice. Forty-eight male C57BL/6J mice were assigned into four groups and fed low-fat diet with free access to water or WPJ, or fed high-fat diet with free access to water or WPJ for 14 weeks. Our results showed that administration of WPJ improved high-fat diet-induced insulin resistance, hepatic steatosis and adipose hypertrophy, but it exerted no influence on body weight gain in mice. Hepatic gene expression analysis indicated that WPJ supplement not only changed the expression profile of genes involved in lipid and cholesterol metabolism (Srebp1, HMGCoR, Cpt1b, HL, Insig1 and Insig2) but also significantly increased the expression levels of FGF21-related genes (Klb, FGFR2, Egr1 and cFos). In conclusion, WPJ protected from diet-induced hepatic steatosis and insulin resistance, which was associated with the improved FGF21 resistance and lipid metabolism.

  8. Chronic Reduction of Plasma Free Fatty Acid Improves Mitochondrial Function and Whole-Body Insulin Sensitivity in Obese and Type 2 Diabetic Individuals

    PubMed Central

    Daniele, Giuseppe; Eldor, Roy; Merovci, Aurora; Clarke, Geoffrey D.; Xiong, Juan; Tripathy, Devjit; Taranova, Anna; Abdul-Ghani, Muhammad

    2014-01-01

    Insulin resistance and dysregulation of free fatty acid (FFA) metabolism are core defects in type 2 diabetic (T2DM) and obese normal glucose tolerant (NGT) individuals. Impaired muscle mitochondrial function (reduced ATP synthesis) also has been described in insulin-resistant T2DM and obese subjects. We examined whether reduction in plasma FFA concentration with acipimox improved ATP synthesis rate and altered reactive oxygen species (ROS) production. Eleven NGT obese and 11 T2DM subjects received 1) OGTT, 2) euglycemic insulin clamp with muscle biopsy, and 3) 1H-magnetic resonance spectroscopy of tibialis anterior muscle before and after acipimox (250 mg every 6 h for 12 days). ATP synthesis rate and ROS generation were measured in mitochondria isolated from muscle tissue ex vivo with chemoluminescence and fluorescence techniques, respectively. Acipimox 1) markedly reduced the fasting plasma FFA concentration and enhanced suppression of plasma FFA during oral glucose tolerance tests and insulin clamp in obese NGT and T2DM subjects and 2) enhanced insulin-mediated muscle glucose disposal and suppression of hepatic glucose production. The improvement in insulin sensitivity was closely correlated with the decrease in plasma FFA in obese NGT (r = 0.81) and T2DM (r = 0.76) subjects (both P < 0.001). Mitochondrial ATP synthesis rate increased by >50% in both obese NGT and T2DM subjects and was strongly correlated with the decrease in plasma FFA and increase in insulin-mediated glucose disposal (both r > 0.70, P < 0.001). Production of ROS did not change after acipimox. Reduction in plasma FFA in obese NGT and T2DM individuals improves mitochondrial ATP synthesis rate, indicating that the mitochondrial defect in insulin-resistant individuals is, at least in part, reversible. PMID:24353180

  9. Serum 25-Hydroxyvitamin D Concentration Is Independently Inversely Associated with Insulin Resistance in the Healthy, Non-Obese Korean Population

    PubMed Central

    Ock, So Young; Ha, Kyoung Hwa; Kim, Bu Kyung; Kim, Hyeon Chang; Shim, Jee-Seon; Lee, Myung Ha; Yoon, Young Me

    2016-01-01

    Background We evaluated the associations between 25-hydroxyvitamin D (25(OH)D) concentrations in serum and insulin resistance in the healthy Korean population. Methods We conducted this cross-sectional analysis in 1,807 healthy Korean people (628 men and 1,179 women) aged 30 to 64 years in the Cardiovascular and Metabolic Disease Etiologic Research Center study. All participants were assessed for 25(OH)D, fasting glucose, and insulin levels, and completed a health examination and lifestyle questionnaire according to standard procedures. Insulin resistance was defined as the homeostasis model assessment insulin resistance higher than the 75 percentile. Results Compared to those in the highest tertile (≥14.3 ng/mL), the odds ratio (OR) for insulin resistance was 1.37 (95% confidence interval [CI], 1.01 to 1.86) for the 1st tertile (<9.7 ng/mL) and 1.19 (95% CI, 0.08 to 1.62) for the 2nd tertile (9.7 to 14.3 ng/mL) after adjusting for age, gender, waist circumference, alcohol consumption, smoking status, physical exercise, season, and cohort. After stratification of the subjects by adiposity, these associations remained only in non-obese subjects (lowest tertile vs. highest tertile, multivariable OR, 1.64; 95% CI, 1.05 to 2.56). Conclusion Serum 25(OH)D has an independent inverse association with insulin resistance in the healthy, non-obese Korean population, even among people with vitamin D insufficiency. PMID:27535642

  10. Prohibitin-induced, obesity-associated insulin resistance and accompanying low-grade inflammation causes NASH and HCC

    PubMed Central

    Ande, Sudharsana R.; Nguyen, K. Hoa; Grégoire Nyomba, B. L.; Mishra, Suresh

    2016-01-01

    Obesity increases the risk for nonalcoholic steatohepatitis (NASH) and hepatocarcinogenesis. However, the underlying mechanisms involved in the disease process remain unclear. Recently, we have developed a transgenic obese mouse model (Mito-Ob) by prohibitin mediated mitochondrial remodeling in adipocytes. The Mito-Ob mice develop obesity in a sex-neutral manner, but obesity-associated adipose inflammation and metabolic dysregulation in a male sex-specific manner. Here we report that with aging, the male Mito-Ob mice spontaneously develop obesity-linked NASH and hepatocellular carcinoma (HCC). In contrast, the female Mito-Ob mice maintained normal glucose and insulin levels and did not develop NASH and HCC. The anti-inflammatory peptide ghrelin was significantly upregulated in the female mice and down regulated in the male mice compared with respective control mice. In addition, a reduction in the markers of mitochondrial content and function was found in the liver of male Mito-Ob mice with NASH/HCC development. We found that ERK1/2 signaling was significantly upregulated whereas STAT3 signaling was significantly down regulated in the tumors from Mito-Ob mice. These data provide a proof-of-concept that the metabolic and inflammatory status of the adipose tissue and their interplay at the systemic and hepatic level play a central role in the pathogenesis of obesity-linked NASH and HCC. PMID:27005704

  11. Metformin Improves Insulin Signaling in Obese Rats via Reduced IKKbeta Action in a Fiber-Type Specific Manner.

    PubMed

    Bikman, Benjamin T; Zheng, Donghai; Kane, Daniel A; Anderson, Ethan J; Woodlief, Tracey L; Price, Jesse W; Dohm, G Lynis; Neufer, P Darrell; Cortright, Ronald N

    2010-01-01

    Metformin is a widely used insulin-sensitizing drug, though its mechanisms are not fully understood. Metformin has been shown to activate AMPK in skeletal muscle; however, its effects on the inhibitor of kappaB kinasebeta (IKKbeta) in this same tissue are unknown. The aim of this study was to (1) determine the ability of metformin to attenuate IKKbeta action, (2) determine whether changes in AMPK activity are associated with changes in IKKbeta action in skeletal muscle, and (3) examine whether changes in AMPK and IKKbeta function are consistent with improved insulin signaling. Lean and obese male Zuckers received either vehicle or metformin by oral gavage daily for four weeks (four groups of eight). Proteins were measured in white gastrocnemius (WG), red gastrocnemius (RG), and soleus. AMPK phosphorylation increased (P < .05) in WG in both lean (57%) and obese (106%), and this was supported by an increase in phospho-ACC in WG. Further, metformin increased IkappaBalpha levels in both WG (150%) and RG (67%) of obese rats, indicative of reduced IKKbeta activity (P < .05), and was associated with reduced IRS1-pSer(307) (30%) in the WG of obese rats (P < .02). From these data we conclude that metformin treatment appears to exert an inhibitory influence on skeletal muscle IKKbeta activity, as evidenced by elevated IkappaBalpha levels and reduced IRS1-Ser(307) phosphorylation in a fiber-type specific manner. PMID:20798864

  12. Interrelationships between changes in anthropometric variables and computed tomography indices of abdominal fat distribution in response to a 1-year physical activity-healthy eating lifestyle modification program in abdominally obese men.

    PubMed

    Villeneuve, Nicole; Pelletier-Beaumont, Emilie; Nazare, Julie-Anne; Lemieux, Isabelle; Alméras, Natalie; Bergeron, Jean; Tremblay, Angelo; Poirier, Paul; Després, Jean-Pierre

    2014-04-01

    The objectives were to (i) measure the effects of a 1-year lifestyle modification program on body fat distribution/anthropometric variables; (ii) determine the interrelationships between changes in all these variables; and (iii) investigate whether there is a selective reduction in deep (DSAT) vs. superficial subcutaneous adipose tissue (SSAT) at the abdominal level following a 1-year lifestyle modification program. Anthropometric variables, body composition and abdominal and midthigh fat distribution were assessed at baseline and after 1 year in 109 sedentary, dyslipidemic and abdominally obese men. Reductions in anthropometric variables, skinfold thicknesses (except the trunk/extremity ratio) and fat mass as well as an increase in fat-free mass were observed after 1 year (p < 0.0001). Decreases in abdominal adipose tissue volumes were also noted (-23%, -26%, -18%, -19%, -17%, p < 0.0001 for total adipose tissue, visceral adipose tissue, subcutaneous adipose tissue, DSAT and SSAT, respectively). Adipose tissue areas at midthigh also decreased (-18%, -18%, -17%, p < 0.0001 for total, deep, and subcutaneous adipose tissue, respectively). A reduction (-9%, p < 0.0001) in low-attenuation muscle area and an increase (+1%, p < 0.05) in normal-attenuation muscle area were also observed. There was a positive relationship between changes in visceral adipose tissue and changes in DSAT (r = 0.65, p < 0.0001) or SSAT (r = 0.63, p < 0.0001). Although absolute changes in DSAT were greater than changes in SSAT, relative changes in both depots were similar, independent of changes in visceral adipose tissue. The 1-year lifestyle modification program therefore improved the body fat distribution pattern and midthigh muscle quality in abdominally obese men.

  13. Sex Differences in Biomarkers Associated With Insulin Resistance in Obese Adolescents: Metabolomic Profiling and Principal Components Analysis

    PubMed Central

    Newbern, Dorothee; Balikcioglu, Metin; Bain, James; Muehlbauer, Michael; Stevens, Robert; Ilkayeva, Olga; Dolinsky, Diana; Armstrong, Sarah; Irizarry, Krystal; Freemark, Michael

    2014-01-01

    Objective: Obesity and insulin resistance (IR) predispose to type 2 diabetes mellitus. Yet only half of obese adolescents have IR and far fewer progress to type 2 diabetes mellitus. We hypothesized that amino acid and fatty acid metabolites may serve as biomarkers or determinants of IR in obese teens. Research Design and Methods: Fasting blood samples were analyzed by tandem mass spectrometry in 82 obese adolescents. A principal components analysis and multiple linear regression models were used to correlate metabolic components with surrogate measures of IR: homeostasis model assessment index of insulin resistance (HOMA-IR), adiponectin, and triglyceride (TG) to high-density lipoprotein (HDL) ratio. Results: Branched-chain amino acid (BCAA) levels and products of BCAA catabolism were higher (P < .01) in males than females with comparable body mass index (BMI) z-score. In multivariate analyses, HOMA-IR in males correlated positively with BMI z-score and a metabolic signature containing BCAA, uric acid, and long-chain acylcarnitines and negatively with byproducts of complete fatty acid oxidation (R2 = 0.659, P < .0001). In contrast, only BMI z-score correlated with HOMA-IR in females. Adiponectin correlated inversely with BCAA and uric acid (R2 = 0.268, P = .0212) in males but not females. TG to HDL ratio correlated with BMI z-score and the BCAA signature in females but not males. Conclusions: BCAA levels and byproducts of BCAA catabolism are higher in obese teenage boys than girls of comparable BMI z-score. A metabolic signature comprising BCAA and uric acid correlates positively with HOMA-IR in males and TG to HDL ratio in females and inversely with adiponectin in males but not females. Likewise, byproducts of fatty acid oxidation associate inversely with HOMA-IR in males but not females. Our findings underscore the roles of sex differences in metabolic function and outcomes in pediatric obesity. PMID:25202817

  14. Unhealthy Phenotype as Indicated by Salivary Biomarkers: Glucose, Insulin, VEGF-A, and IL-12p70 in Obese Kuwaiti Adolescents

    PubMed Central

    Hartman, Mor-Li; Goodson, J. Max; Shi, Ping; Vargas, Jorel; Yaskell, Tina; Stephens, Danielle; Cugini, Maryann; Hasturk, Hatice; Barake, Roula; Alsmadi, Osama; Al-Mutawa, Sabiha; Ariga, Jitendra; Soparkar, Pramod; Behbehani, Jawad; Behbehani, Kazem; Welty, Francine

    2016-01-01

    Objective. Here, we investigated the relationships between obesity and the salivary concentrations of insulin, glucose, and 20 metabolic biomarkers in Kuwaiti adolescents. Previously, we have shown that certain salivary metabolic markers can act as surrogates for blood concentrations. Methods. Salivary samples of whole saliva were collected from 8,317 adolescents. Salivary glucose concentration was measured by a high-sensitivity glucose oxidase method implemented on a robotic chemical analyzer. The concentration of salivary insulin and 20 other metabolic biomarkers was assayed in 744 randomly selected saliva samples by multiplexed bead-based immunoassay. Results. Obesity was seen in 26.5% of the adolescents. Salivary insulin predicting hyperinsulinemia occurred in 4.3% of normal-weight adolescents, 8.3% of overweight adolescents, and 25.7% of obese adolescents (p < 0.0001). Salivary glucose predicting hyperglycemia was found in only 3% of obese children and was not predictive (p = 0.89). Elevated salivary glucose and insulin occurring together was associated with elevated vascular endothelial growth factor and reduced salivary interleukin-12. Conclusion. Considering the surrogate nature of salivary insulin and glucose, this study suggests that elevated insulin may be a dominant sign of metabolic disease in adolescent populations. It also appears that a proangiogenic environment may accompany elevated glucose in obese adolescents. PMID:27069678

  15. Abdominal Obesity and Association With Atherosclerosis Risk Factors: The Uberlândia Heart Study.

    PubMed

    Roever, Leonardo S; Resende, Elmiro S; Diniz, Angélica L D; Penha-Silva, Nilson; Veloso, Fernando C; Casella-Filho, Antonio; Dourado, Paulo M M; Chagas, Antonio C P

    2016-03-01

    Ectopic visceral fat (VF) and subcutaneous fat (SCF) are associated with cardiovascular risk factors. Gender differences in the correlations of cardiovascular disease risk factors and ectopic fat in the Brazilian population still lacking. Cross-sectional study with 101 volunteers (50.49% men; mean age 56.5 ± 18, range 19-74 years) drawn from the Uberlândia Heart Study underwent ultrasonography assessment of abdominal visceral adipose tissue with convex transducer of 3.5 MHz of frequency. The thickness of VF was ultrasonographically measured by the distance between the inner face of the abdominal muscle and the posterior face of abdominal aorta, 1 cm above the umbilicus. The SCF thickness was measured with a 7.5 MHz linear transducer transversely positioned 1 cm above the umbilical scar. The exams were always performed by the same examiner. Ectopic fat volumes were examined in relation to waist circumference, blood pressure, and metabolic risk factors. The VF was significantly associated with the levels of triglycerides (P < 0.01, r = 0.10), HDL cholesterol (P < 0.005, r = 0.15), total cholesterol (P < 0.01, r = 0.10), waist circumference (P < 0.0001, r = 0.43), systolic blood pressure (P < 0.001, r = 0.41), and diastolic blood pressure (P < 0.001, r = 0.32) in women, and with the levels of triglycerides (P < 0.002, r = 0,14), HDL cholesterol (P < 0.032, r = 0.07), glucose (P < 0.001, r = 0.15), alanine aminotransferase (ALT) (P < 0.008, r = 0.12), gamma-GT (P < 0.001, r = 0.30), waist circumference (P < 0.001, r = 0.52), systolic blood pressure (P < 0.001, r = 0.32), and diastolic blood pressure (P < 0.001, r = 0.26) in men. SCF was significantly associated with the levels of triglycerides (P < 0.01, r = 0.34), LDL cholesterol (P < 0.001, r = 0.36), total cholesterol (P < 0.05, r = 0.36), waist circumference (P

  16. The glucose-dependent insulinotropic polypeptide and glucose-stimulated insulin response to exercise training and diet in obesity.

    PubMed

    Kelly, Karen R; Brooks, Latina M; Solomon, Thomas P J; Kashyap, Sangeeta R; O'Leary, Valerie B; Kirwan, John P

    2009-06-01

    Aging and obesity are characterized by decreased beta-cell sensitivity and defects in the potentiation of nutrient-stimulated insulin secretion by GIP. Exercise and diet are known to improve glucose metabolism and the pancreatic insulin response to glucose, and this effect may be mediated through the incretin effect of GIP. The purpose of this study was to assess the effects of a 12-wk exercise training intervention (5 days/wk, 60 min/day, 75% Vo(2 max)) combined with a eucaloric (EX, n = 10) or hypocaloric (EX-HYPO, pre: 1,945 +/- 190, post: 1,269 +/- 70, kcal/day; n = 9) diet on the GIP response to glucose in older (66.8 +/- 1.5 yr), obese (34.4 +/- 1.7 kg/m(2)) adults with impaired glucose tolerance. In addition to GIP, plasma PYY(3-36), insulin, and glucose responses were measured during a 3-h, 75-g oral glucose tolerance test. Both interventions led to a significant improvement in Vo(2 max) (P < 0.05). Weight loss (kg) was significant in both groups but was greater after EX-HYPO (-8.3 +/- 1.1 vs. -2.8 +/- 0.5, P = 0.002). The glucose-stimulated insulin response was reduced after EX-HYPO (P = 0.02), as was the glucose-stimulated GIP response (P < 0.05). Furthermore, after the intervention, changes in insulin (DeltaI(0-30)/DeltaG(0-30)) and GIP (Delta(0-30)) secretion were correlated (r = 0.69, P = 0.05). The PYY(3-36) (Delta(0-30)) response to glucose was increased after both interventions (P < 0.05). We conclude that 1) a combination of caloric restriction and exercise reduces the GIP response to ingested glucose, 2) GIP may mediate the attenuated glucose-stimulated insulin response after exercise/diet interventions, and 3) the increased PYY(3-36) response represents an improved capacity to regulate satiety and potentially body weight in older, obese, insulin-resistant adults.

  17. γδ T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice.

    PubMed

    Mehta, Pooja; Nuotio-Antar, Alli Martina; Smith, C Wayne

    2015-01-01

    γδ T cells are resident in AT and increase during diet-induced obesity. Their possible contribution to the inflammatory response that accompanies diet-induced obesity was investigated in mice after a 5 to 10 week milk HFD. The HFD resulted in significant increases in CD44(hi), CD62L(lo), and TNF-α(+) γδ T cells in eAT of WT mice. Mice deficient in all γδ T cells (TCRδ(-/-)) or only Vγ4 and Vγ6 subsets (Vγ4/6(-/-)) were compared with WT mice with regard to proinflammatory cytokine production and macrophage accumulation in eAT. Obesity among these mouse strains did not differ, but obese TCRδ(-/-) and Vγ4/6(-/-) mice had significantly reduced eAT expression of F4/80, a macrophage marker, and inflammatory mediators CCL2 and IL-6 compared with WT mice. Obese TCRδ(-/-) mice had significantly reduced CD11c(+) and TNF-α(+) macrophage accumulation in eAT after 5 and 10 weeks on the HFD, and obese Vγ4/6(-/-) mice had significantly increased CD206(+) macrophages in eAT after 5 weeks on the diet and significantly reduced macrophages after 10 weeks. Obese TCRδ(-/-) mice had significant reductions in systemic insulin resistance and inflammation in liver and skeletal muscle after longer-term HFD feeding (10 and 24 weeks). In vitro studies revealed that isolated γδ T cells directly stimulated RAW264.7 macrophage TNF-α expression but did not stimulate inflammatory mediator expression in 3T3-L1 adipocytes. These findings are consistent with a role for γδ T cells in the proinflammatory response that accompanies diet-induced obesity.

  18. A novel ALMS1 splice mutation in a non-obese juvenile-onset insulin-dependent syndromic diabetic patient.

    PubMed

    Sanyoura, May; Woudstra, Cédric; Halaby, George; Baz, Patrick; Senée, Valérie; Guillausseau, Pierre-Jean; Zalloua, Pierre; Julier, Cécile

    2014-01-01

    Insulin-dependent juvenile-onset diabetes may occur in the context of rare syndromic presentations suggesting monogenic inheritance rather than common multifactorial autoimmune type 1 diabetes. Here, we report the case of a Lebanese patient diagnosed with juvenile-onset insulin-dependent diabetes presenting ketoacidosis, early-onset retinopathy with optic atrophy, hearing loss, diabetes insipidus, epilepsy, and normal weight and stature, who later developed insulin resistance. Despite similarities with Wolfram syndrome, we excluded the WFS1 gene as responsible for this disease. Using combined linkage and candidate gene study, we selected ALMS1, responsible for Alström syndrome, as a candidate gene. We identified a novel splice mutation in intron 18 located 3 bp before the intron-exon junction (IVS18-3T>G), resulting in exon 19 skipping and consequent frameshift generating a truncated protein (V3958fs3964X). The clinical presentation of the patient significantly differed from typical Alström syndrome by the absence of truncal obesity and short stature, and by the presence of ketoacidotic insulin-dependent diabetes, optic atrophy and diabetes insipidus. Our observation broadens the clinical spectrum of Alström syndrome and suggests that ALMS1 mutations may be considered in patients who initially present with an acute onset of insulin-dependent diabetes.

  19. High serum selenium levels are associated with increased risk for diabetes mellitus independent of central obesity and insulin resistance

    PubMed Central

    Lu, Chia-Wen; Chang, Hao-Hsiang; Yang, Kuen-Cheh; Kuo, Chia-Sheng; Lee, Long-Teng; Huang, Kuo-Chin

    2016-01-01

    Objective Selenium is an essential micronutrient for human health. Although many observational and interventional studies have examined the associations between selenium and diabetes mellitus, the findings were inconclusive. This study aimed to investigate the relationship between serum selenium levels and prevalence of diabetes, and correlated the relationship to insulin resistance and central obesity. Research design and methods This was a hospital-based case–control study of 847 adults aged more than 40 years (diabetes: non-diabetes =1:2) in Northern Taiwan. Serum selenium was measured by an inductively coupled plasma-mass spectrometer. The association between serum selenium and diabetes was examined using multivariate logistic regression analyses. Results After adjusting for age, gender, current smoking, current drinking, and physical activity, the ORs (95% CI, p value) of having diabetes in the second (Q2), third (Q3), and fourth (Q4) selenium quartile groups were 1.24 (95% CI 0.78 to 1.98, p>0.05), 1.90 (95% CI 1.22 to 2.97, p<0.05), and 5.11 (95% CI 3.27 to 8.00, p<0.001), respectively, compared with the first (Q1) quartile group. Further adjustments for waist circumference and homeostatic model assessment-insulin resistance (HOMA-IR) largely removed the association of serum selenium levels with diabetes but not in the highest quartile (compared with Q1, Q3: 1.57, 95% CI 0.91 to 2.70, Q4: 3.79, 95% CI 2.17 to 6.32). Conclusions We found that serum selenium levels were positively associated with prevalence of diabetes. This is the first human study to link insulin resistance and central obesity to the association between selenium and diabetes. Furthermore, the association between selenium and diabetes was independent of insulin resistance and central obesity at high serum selenium levels. The mechanism behind warrants further confirmation. PMID:27547419

  20. Exercise and dietary change ameliorate high fat diet induced obesity and insulin resistance via mTOR signaling pathway

    PubMed Central

    Bae, Ju Yong; Shin, Ki Ok; Woo, Jinhee; Woo, Sang Heon; Jang, Ki Soeng; Lee, Yul Hyo; Kang, Sunghwun

    2016-01-01

    [Purpose] The purpose of this study was to investigate the effect of exercise and dietary change on obesity and insulin resistance and mTOR signaling protein levels in skeletal muscles of obese rats. [Methods] Sixty male Sprague-Dawley rats were divided into CO (Normal diet) and HF (High Fat diet) groups in order to induce obesity for 15 weeks. The rats were then subdivided into CO, COT (CO + Training), HF, HFT (HF + Training), HFND (Dietary change), and HFNDT (HFND + Training) groups (10 rats / group). The training groups underwent moderate-intensity treadmill exercise for 8 weeks, after which soleus muscles were excised and analyzed. Data was statistically analyzed by independent t-test and One-way ANOVA tests with a 0.05 significance level. [Results] Fasting blood glucose, plasma insulin, and HOMA-IR in the HF group were significantly higher, as compared with other groups (p <.05). Protein levels of insulin receptor subunit-1 (IRS-1), IRS-2, and p-Akt were significantly higher in the HFT, HFND, and HFNDT groups, as compared with HF group. In addition, the protein levels of the mammalian target of rapamycin complex 1 (mTORC1) and ribosomal S6 protein kinase 1 were significantly decreased by exercise and dietary change (p <.05). However, mTORC2 and phosphoinositide 3-kinase were significantly increased (p <.05). [Conclusion] In summary, despite the negative impact of continuous high fat intake, regular exercise and dietary change showed a positive effect on insulin resistance and mTOR signaling protein levels. PMID:27508151

  1. Inverse Relationship between the Inflammatory Marker Pentraxin-3, Fat Body Mass, and Abdominal Obesity in End-Stage Renal Disease

    PubMed Central

    Miyamoto, Tetsu; Rashid Qureshi, Abdul; Heimbürger, Olof; Bárány, Peter; Carrero, Karin; Sjöberg, Bodil; Lindholm, Bengt; Stenvinkel, Peter

    2011-01-01

    Summary Background and objectives Pentraxin-3 (PTX3) belongs to the same pentraxin superfamily of acute-phase reactants as C-reactive protein (CRP). Abdominal fat accumulation in ESRD is considered a chronic inflammatory state, but the relationship of PTX3 to this phenomenon is unknown. This study assesses plausible associations between PTX3 and surrogates of fat mass deposits in dialysis patients. Design, setting, participants, & measurements Circulating levels of PTX3, CRP, and IL-6 were cross-sectionally analyzed in relation to anthropometric and nutritional surrogate markers of fat tissue in two cohorts comprising 156 prevalent hemodialysis (HD) and 216 incident dialysis patients. Results In both cohorts, PTX3 was negatively associated with body mass index (BMI) and fat body mass index (FBMI) derived from anthropometrics and leptin, whereas there was a positive association with adiponectin. In prevalent HD patients, those with larger waist circumference (above gender-specific median values) had lower PTX3, higher CRP, and higher IL-6 levels. This was also true in multivariate analyses. In both cohorts, multivariate regression analyses showed that PTX3 was negatively and CRP (or IL-6) was positively associated with FBMI. Conclusions Although CRP and IL-6 were directly associated with body fat, PTX3 levels showed negative correlations with surrogates of adipose tissue in two independent cohorts of ESRD patients. Understanding the underlying reasons behind these opposite associations may have clinical relevance given the survival advantage described for obese patients on dialysis. PMID:22157708

  2. FGF21 improves cognition by restored synaptic plasticity, dendritic spine density, brain mitochondrial function and cell apoptosis in obese-insulin resistant male rats.

    PubMed

    Sa-Nguanmoo, Piangkwan; Tanajak, Pongpan; Kerdphoo, Sasiwan; Satjaritanun, Pattarapong; Wang, Xiaojie; Liang, Guang; Li, Xiaokun; Jiang, Chao; Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2016-09-01

    Fibroblast growth factor 21 (FGF21) is an endocrine hormone which exerts beneficial effects on metabolic regulation in obese and diabetic models. However, the effect of FGF21 on cognition in obese-insulin resistant rats has not been investigated. We hypothesized that FGF21 prevented cognitive decline in obese-insulin resistant rats by improving hippocampal synaptic plasticity, dendritic spine density, brain mitochondrial function and brain FGF21 signaling as well as decreasing brain cell apoptosis. Eighteen male Wistar rats were divided into two groups, and received either a normal diet (ND) (n=6) or a high fat diet (HFD) (n=12) for 12weeks. At week 13, the HFD-fed rats were subdivided into two subgroups (n=6/subgroup) to receive either vehicle or recombinant human FGF21 (0.1mg/kg/day) for four weeks. ND-fed rats were given vehicle for four weeks. At the end of the treatment, cognitive function, metabolic parameters, pro-inflammatory markers, brain mitochondrial function, cell apoptosis, hippocampal synaptic plasticity, dendritic spine density and brain FGF21 signaling were determined. The results showed that vehicle-treated HFD-fed rats developed obese-insulin resistance and cognitive decline with impaired hippocampal synaptic plasticity, decreased dendritic spine density, brain mitochondrial dysfunction and increased brain cell apoptosis. Impaired brain FGF 21 signaling was found in these obese-insulin resistant rats. FGF21-treated obese-insulin resistant rats had improved peripheral insulin sensitivity, increased hippocampal synaptic plasticity, increased dendritic spine density, restored brain mitochondrial function, attenuated brain cells apoptosis and increased brain FGF21 signaling, leading to a prevention of cognitive decline. These findings suggest that FGF21 treatment exerts neuroprotection in obese-insulin resistant rats. PMID:27566237

  3. [Systolic pressure, abdominal obesity and body fat, metabolic syndrome predictors in Spanish preschoolers].

    PubMed

    Gutiérrez Hervás, Ana Isabel; Rizo Baeza, María Mercedes; Martínez Amorós, Natalia; Cortés Castell, Ernesto

    2015-05-01

    Se plantea como objetivo determinar la presencia de predictores de síndrome metabólico en niños de 2 a 7 años en relación a su estado nutricional. Método: Estudio descriptivo con análisis cuantitativo en 260 niños de 2-7 años (135 niñas y 125 niños), 66% del total censados. Se midieron parámetros antropométricos y tensión arterial y se calcularon IMC, grasa corporal según Hoffman e índice cintura-talla (ICT). Se realizaron subgrupos con Z-Score del IMC según edad y sexo (bajo peso, normopeso, sobrepeso y obesidad), según grasa corporal (normal y con exceso), ICT (normal y obesidad abdominal) y tensión sistólica (normotensos e hipertensos según edad y sexo). Se utilizó como variable principal la clasificación según Z-Score del IMC. Resultados: La prevalencia combinada de sobrepeso y obesidad fue del 27%, sin diferencias por sexo. El estado nutricional relacionó significativamente con tensión arterial, grasa corporal e índice cintura-talla. Mayor porcentaje de obesos con tensión arterial sistólica alta que de normonutridos (OR=4.1; IC95% 1.7-9.8; p.

  4. Prevalence of male secondary hypogonadism in moderate to severe obesity and its relationship with insulin resistance and excess body weight.

    PubMed

    Calderón, Berniza; Gómez-Martín, Jesús M; Vega-Piñero, Belén; Martín-Hidalgo, Antonia; Galindo, Julio; Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F; Botella-Carretero, José I

    2016-01-01

    To study the prevalence of male obesity-secondary hypogonadism (MOSH) in patients with moderate to severe obesity, we performed a prospective prevalence study including 100 male patients with moderate to severe obesity at a university tertiary hospital. Total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations among others were assayed in all patients. Serum-free testosterone (FT) concentration was calculated from TT and SHBG levels. Semen analysis was conducted in 31 patients. We found a prevalence of 45% (95% CI: 35-55%) when considering decreased TT and/or FT concentrations. Serum concentrations of TT were correlated negatively with glucose (r = -0.328, p < 0.001) and insulin resistance (r = -0.261, p = 0.011). The same occurred with FT and glucose (r = -0.340, p < 0.001) and insulin resistance (r = -0.246, p = 0.016). Sixty-two percent (95% CI: 39-85%) of the patients with seminogram also presented abnormal results in semen analysis. The frequencies of low TT or low FT values were similar in patients with abnormal or normal semen analysis (p = 0.646 and p = 0.346, respectively). Ejaculate volume inversely correlated with BMI (ρ = -0.400, p = 0.029) and with excess body weight (ρ = -0.464, p = 0.010). Our data show the prevalence of MOSH in patients with moderate to severe obesity is high. Low circulating testosterone is associated with insulin resistance and low ejaculate volume with higher BMI and excess body weight. Semen analysis must be performed in these patients when considering fertility whether or not presenting low circulating testosterone. PMID:26663756

  5. An Evaluation of Acylated Ghrelin and Obestatin Levels in Childhood Obesity and Their Association with Insulin Resistance, Metabolic Syndrome, and Oxidative Stress

    PubMed Central

    Razzaghy-Azar, Maryam; Nourbakhsh, Mitra; Pourmoteabed, Abdolreza; Nourbakhsh, Mona; Ilbeigi, Davod; Khosravi, Mohsen

    2016-01-01

    Background: Ghrelin is a 28-amino acid peptide with an orexigenic property, which is predominantly produced by the stomach. Acylated ghrelin is the active form of this hormone. Obestatin is a 23-amino acid peptide which is produced by post-translational modification of a protein precursor that also produces ghrelin. Obestatin has the opposite effect of ghrelin on food intake. The aim of this study was to evaluate acylated ghrelin and obestatin levels and their ratio in obese and normal-weight children and adolescents, and their association with metabolic syndrome (MetS) parameters. Methods: Serum acyl-ghrelin, obestatin, leptin, insulin, fasting plasma glucose (FPG), lipid profile, and malondialdehyde (MDA) were evaluated in 73 children and adolescents (42 obese and 31 control). Insulin resistance was calculated by a homeostasis model assessment of insulin resistance (HOMA-IR). MetS was determined according to IDF criteria. Results: Acyl-ghrelin levels were significantly lower in obese subjects compared to the control group and lower in obese children with MetS compared to obese subjects without MetS. Obestatin was significantly higher in obese subjects compared to that of the control, but it did not differ significantly among those with or without MetS. Acyl-ghrelin to obestatin ratio was significantly lower in obese subjects compared to that in normal subjects. Acyl-ghrelin showed significant negative and obestatin showed significant positive correlations with body mass index (BMI), BMI Z-score, leptin, insulin, and HOMA-IR. Acyl-ghrelin had a significant negative correlation with MDA as an index of oxidative stress. Conclusion: Ghrelin is decreased and obestatin is elevated in obesity. Both of these hormones are associated with insulin resistance, and ghrelin is associated with oxidative stress. The balance between ghrelin and obestatin seems to be disturbed in obesity. PMID:27348010

  6. Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7

    SciTech Connect

    Duggirala, R.; Stern, M.P.; Reinhart, L.J.

    1996-09-01

    Despite the evidence that human obesity has strong genetic determinants, efforts at identifying specific genes that influence human obesity have largely been unsuccessful. Using the sibship data obtained from 32 low-income Mexican American pedigrees ascertained on a type II diabetic proband and a multipoint variance-components method, we tested for linkage between various obesity-related traits plus associated metabolic traits and 15 markers on human chromosome 7. We found evidence for linkage between markers in the OB gene region and various traits, as follows: D7S514 and extremity skinfolds (LOD = 3.1), human carboxypeptidase A1 (HCPA1) and 32,33-split proinsulin level (LOD = 4.2), and HCPA1 and proinsulin level (LOD = 3.2). A putative susceptibility locus linked to the marker D7S514 explained 56% of the total phenotypic variation in extremity skinfolds. Variation at the HCPA1 locus explained 64% of phenotypic variation in proinsulin level and {approximately}73% of phenotypic variation in split proinsulin concentration, respectively. Weaker evidence for linkage to several other obesity-related traits (e.g., waist circumference, body-mass index, fat mass by bioimpedance, etc.) was observed for a genetic location, which is {approximately}15 cM telomeric to OB. In conclusion, our study reveals that the OB region plays a significant role in determining the phenotypic variation of both insulin precursors and obesity-related traits, at least in Mexican Americans. 66 refs., 3 figs., 4 tabs.

  7. Intensive lifestyle intervention including high-intensity interval training program improves insulin resistance and fasting plasma glucose in obese patients☆

    PubMed Central

    Marquis-Gravel, Guillaume; Hayami, Douglas; Juneau, Martin; Nigam, Anil; Guilbeault, Valérie; Latour, Élise; Gayda, Mathieu

    2015-01-01

    Objectives To analyze the effects of a long-term intensive lifestyle intervention including high-intensity interval training (HIIT) and Mediterranean diet (MedD) counseling on glycemic control parameters, insulin resistance and β-cell function in obese subjects. Methods The glycemic control parameters (fasting plasma glucose, glycated hemoglobin), insulin resistance, and β-cell function of 72 obese subjects (54 women; mean age = 53 ± 9 years) were assessed at baseline and upon completion of a 9-month intensive lifestyle intervention program conducted at the cardiovascular prevention and rehabilitation center of the Montreal Heart Institute, from 2009 to 2012. The program included 2–3 weekly supervised exercise training sessions (HIIT and resistance exercise), combined to MedD counseling. Results Fasting plasma glucose (FPG) (mmol/L) (before: 5.5 ± 0.9; after: 5.2 ± 0.6; P < 0.0001), fasting insulin (pmol/L) (before: 98 ± 57; after: 82 ± 43; P = 0.003), and insulin resistance, as assessed by the HOMA-IR score (before: 3.6 ± 2.5; after: 2.8 ± 1.6; P = 0.0008) significantly improved, but not HbA1c (%) (before: 5.72 ± 0.55; after: 5.69 ± 0.39; P = 0.448), nor β-cell function (HOMA-β, %) (before: 149 ± 78; after: 144 ± 75; P = 0.58). Conclusion Following a 9-month intensive lifestyle intervention combining HIIT and MedD counseling, obese subjects experienced significant improvements of FPG and insulin resistance. This is the first study to expose the effects of a long-term program combining HIIT and MedD on glycemic control parameters among obese subjects. PMID:26844086

  8. Efficacy of two different materials used in auricular acupressure on weight reduction and abdominal obesity.

    PubMed

    Hsieh, Ching Hsiu; Su, Tsann-Juu; Fang, Yu-Wen; Chou, Pei-Hsuan

    2012-01-01

    The current study was designed to test the efficacy of different materials used in an auricular acupressure program on weight reduction, changes to waist circumference and waist-to-hip ratio. This study used a randomized design with two groups who were treated with auricular acupressure using Semen Vaccariae or the Japanese Magnetic Pearl. Both groups consisted of Asian young adults with a waist circumference ≥ 80 cm in the females and ≥ 90 cm in the males. At completion of the eight-week treatment period, the total sample size was 56 young adults who ranged in age from 18 to 20 years old. Each participant was met with weekly for ten-minute sessions during which ear acupressure treatment was performed. Sessions continued for eight weeks wherein both groups received acupressure with the Japanese Magnetic Pearl or Semen Vaccariae on the ear acupoints. While both groups showed significant reductions (p ≤ 0.05) to body weight and waist circumference after eight weeks of treatments, the group treated with Semen Vaccariae group showed a more effective weight loss over the short term. Given that auricular acupressure is a safe and cost-effective treatment for weight loss, our results suggest that auricular acupressure is a reasonable option for the treatment of overweight and obesity in young adults. PMID:22809026

  9. Effects of the New Dual PPARα/δ Agonist GFT505 on Lipid and Glucose Homeostasis in Abdominally Obese Patients With Combined Dyslipidemia or Impaired Glucose Metabolism

    PubMed Central

    Cariou, Bertrand; Zaïr, Yassine; Staels, Bart; Bruckert, Eric

    2011-01-01

    OBJECTIVE We evaluated the metabolic effects and tolerability of GFT505, a novel dual peroxisome proliferator–activated receptor α/δ agonist, in abdominally obese patients with either combined dyslipidemia or prediabetes. RESEARCH DESIGN AND METHODS The S1 study was conducted in 94 patients with combined dyslipidemia while the S2 study was conducted in 47 patients with prediabetes. Participants were randomly assigned in a double-blind manner to GFT505 at 80 mg/day or placebo for 28 (S1) or 35 (S2) days. Primary efficacy end points were changes from baseline at week 4 in both fasting plasma triglycerides and HDL cholesterol in the S1 group and 2-h glucose upon oral glucose tolerance test in the S2 group. RESULTS In comparison with placebo, GFT505 significantly reduced fasting plasma triglycerides (S1: least squares means −16.7% [95% one-sided CI −∞ to −5.3], P = 0.005; S2: −24.8% [−∞ to −10.5], P = 0.0003) and increased HDL cholesterol (S1: 7.8% [3.0 to ∞], P = 0.004; S2: 9.3% [1.7 to ∞], P = 0.009) in both studies, whereas LDL cholesterol only decreased in S2 (−11.0% [ −∞ to −3.5], P = 0.002). In S2, GFT505 did not reduce 2-h glucose (−0.52 mmol/L [−∞ to 0.61], P = 0.18) but led to a significant decrease of homeostasis model assessment of insulin resistance (−31.4% [−∞ to 12.5], P = 0.001), fasting plasma glucose (−0.37 mmol/L [−∞ to −0.10], P = 0.01) and fructosamine (−3.6% [−∞ to −0.20], P = 0.02). GFT505 also reduced γ glutamyl transferase levels in both studies (S1: −19.9% [−∞ to −12.8], P < 0.0001; S2: −15.1% [−∞ to −1.1], P = 0.004). No specific adverse safety signals were reported during the studies. CONCLUSIONS GFT505 may be considered a new drug candidate for the treatment of lipid and glucose disorders associated with the metabolic syndrome. PMID:21816979

  10. Metabolic disturbances connecting obesity and depression

    PubMed Central

    Hryhorczuk, Cecile; Sharma, Sandeep; Fulton, Stephanie E.

    2013-01-01

    Obesity markedly increases the odds of developing depression. Depressed mood not only impairs motivation, quality of life and overall functioning but also increases the risks of obesity complications. Abdominal obesity is a better predictor of depression and anxiety risk than overall adipose mass. A growing amount of research suggests that metabolic abnormalities stemming from central obesity that lead to metabolic disease may also be responsible for the increased incidence of depression in obesity. As reviewed here, a higher mass of dysfunctional adipose tissue is associated with several metabolic disturbances that are either directly or indirectly implicated in the control of emotions and mood. To better comprehend the development of depression in obesity, this review pulls together select findings addressing the link between adiposity, diet and negative emotional states and discusses the evidence that alterations in glucocorticoids, adipose-derived hormones, insulin and inflammatory signaling that are characteristic of central obesity may be involved. PMID:24109426

  11. Insulin Resistance, Microbiota, and Fat Distribution Changes by a New Model of Vertical Sleeve Gastrectomy in Obese Rats.

    PubMed

    Basso, Nicola; Soricelli, Emanuele; Castagneto-Gissey, Lidia; Casella, Giovanni; Albanese, Davide; Fava, Francesca; Donati, Claudio; Tuohy, Kieran; Angelini, Giulia; La Neve, Federica; Severino, Anna; Kamvissi-Lorenz, Virginia; Birkenfeld, Andrea L; Bornstein, Stefan; Manco, Melania; Mingrone, Geltrude

    2016-10-01

    Metabolic surgery improves insulin resistance and type 2 diabetes possibly because of weight loss. We performed a novel sleeve gastrectomy in rats that resects ∼80% of the glandular portion, leaving the forestomach almost intact (glandular gastrectomy [GG]) and compared subsequent metabolic remodeling with a sham operation. GG did not affect body weight, at least after 10 weeks; improved hepatic and peripheral insulin sensitivity likely through increased Akt, glycogen synthase kinase 3, and AMPK phosphorylation; and reduced ectopic fat deposition and hepatic glycogen overaccumulation. Body adipose tissue was redistributed, with reduction of intraabdominal fat. We found a reduction of circulating ghrelin levels, increased GLP-1 plasma concentration, and remodeling of gut microbiome diversity characterized by a lower relative abundance of Ruminococcus and a higher relative abundance of Lactobacillus and Collinsella These data suggest that at least in rat, the glandular stomach plays a central role in the improvement of insulin resistance, even if obesity persists. GG provides a new model of the metabolically healthy obese phenotype. PMID:27431457

  12. Insulin Resistance, Microbiota, and Fat Distribution Changes by a New Model of Vertical Sleeve Gastrectomy in Obese Rats.

    PubMed

    Basso, Nicola; Soricelli, Emanuele; Castagneto-Gissey, Lidia; Casella, Giovanni; Albanese, Davide; Fava, Francesca; Donati, Claudio; Tuohy, Kieran; Angelini, Giulia; La Neve, Federica; Severino, Anna; Kamvissi-Lorenz, Virginia; Birkenfeld, Andrea L; Bornstein, Stefan; Manco, Melania; Mingrone, Geltrude

    2016-10-01

    Metabolic surgery improves insulin resistance and type 2 diabetes possibly because of weight loss. We performed a novel sleeve gastrectomy in rats that resects ∼80% of the glandular portion, leaving the forestomach almost intact (glandular gastrectomy [GG]) and compared subsequent metabolic remodeling with a sham operation. GG did not affect body weight, at least after 10 weeks; improved hepatic and peripheral insulin sensitivity likely through increased Akt, glycogen synthase kinase 3, and AMPK phosphorylation; and reduced ectopic fat deposition and hepatic glycogen overaccumulation. Body adipose tissue was redistributed, with reduction of intraabdominal fat. We found a reduction of circulating ghrelin levels, increased GLP-1 plasma concentration, and remodeling of gut microbiome diversity characterized by a lower relative abundance of Ruminococcus and a higher relative abundance of Lactobacillus and Collinsella These data suggest that at least in rat, the glandular stomach plays a central role in the improvement of insulin resistance, even if obesity persists. GG provides a new model of the metabolically healthy obese phenotype.

  13. Mechanisms of Obesity-Induced Inflammation and Insulin Resistance: Insights into the Emerging Role of Nutritional Strategies

    PubMed Central

    McArdle, Maeve A.; Finucane, Orla M.; Connaughton, Ruth M.; McMorrow, Aoibheann M.; Roche, Helen M.

    2013-01-01

    Obesity and associated chronic inflammation initiate a state of insulin resistance (IR). The secretion of chemoattractants such as MCP-1 and MIF and of cytokines IL-6, TNF-α, and IL-1β, draw immune cells including dendritic cells, T cells, and macrophages into adipose tissue (AT). Dysfunctional AT lipid metabolism leads to increased circulating free fatty acids, initiating inflammatory signaling cascades in the population of infiltrating cells. A feedback loop of pro-inflammatory cytokines exacerbates this pathological state, driving further immune cell infiltration and cytokine secretion and disrupts the insulin signaling cascade. Disruption of normal AT function is causative of defects in hepatic and skeletal muscle glucose homeostasis, resulting in systemic IR and ultimately the development of type 2 diabetes. Pharmaceutical strategies that target the inflammatory milieu may have some potential; however there are a number of safety concerns surrounding such pharmaceutical approaches. Nutritional anti-inflammatory interventions could offer a more suitable long-term alternative; whilst they may be less potent than some pharmaceutical anti-inflammatory agents, this may be advantageous for long-term therapy. This review will investigate obese AT biology, initiation of the inflammatory, and insulin resistant environment; and the mechanisms through which dietary anti-inflammatory components/functional nutrients may be beneficial. PMID:23675368

  14. Purified Betacyanins from Hylocereus undatus Peel Ameliorate Obesity and Insulin Resistance in High-Fat-Diet-Fed Mice.

    PubMed

    Song, Haizhao; Chu, Qiang; Xu, Dongdong; Xu, Yang; Zheng, Xiaodong

    2016-01-13

    Natural bioactive compounds in food have been shown to be beneficial in preventing the development of obesity, diabetes, and other metabolic diseases. Increasing evidence indicates that betacyanins possess free-radical-scavenging and antioxidant activities, suggesting their beneficial effects on metabolic disorders. The main objective of this study was to isolate and identify the betaycanins from Hylocereus undatus (white-fleshed pitaya) peel and evaluate their ability to ameliorate obesity, insulin resistance, and hepatic steatosis in high-fat-diet (HFD)-induced obese mice. The purified pitaya peel betacyanins (PPBNs) were identified by liquid chromatography/tandem mass spectrometry (LC/MS/MS), and the male C57BL/6 mice were fed a low-fat diet, HFD, or HFD supplemented with PPBNs for 14 weeks. Our results showed that the white-fleshed pitaya peel contains 14 kinds of betacyanins and dietary PPBNs reduced HFD-induced body weight gain and ameliorated adipose tissue hypertrophy, hepatosteatosis, glucose intolerance, and insulin resistance. Moreover, the hepatic gene expression analysis indicated that PPBN supplementation increased the expression levels of lipid-metabolism-related genes (AdipoR2, Cpt1a, Cpt1b, Acox1, PPARγ, Insig1, and Insig2) and FGF21-related genes (β-Klotho and FGFR1/2) but decreased the expression level of Fads2, Fas, and FGF21, suggesting that the protective effect of PPBNs might be associated with the induced fatty acid oxidation, decreased fatty acid biosynthesis, and alleviated FGF21 resistance.

  15. Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice

    PubMed Central

    Satoh, Masashi; Hoshino, Miyuki; Fujita, Koki; Iizuka, Misao; Fujii, Satoshi; Clingan, Christopher S.; Van Kaer, Luc; Iwabuchi, Kazuya

    2016-01-01

    It has been shown that CD1d expression and glycolipid-reactive, CD1d-restricted NKT cells exacerbate the development of obesity and insulin resistance in mice. However, the relevant CD1d-expressing cells that influence the effects of NKT cells on the progression of obesity remain incompletely defined. In this study, we have demonstrated that 3T3-L1 adipocytes can present endogenous ligands to NKT cells, leading to IFN-γ production, which in turn, stimulated 3T3-L1 adipocytes to enhance expression of CD1d and CCL2, and decrease expression of adiponectin. Furthermore, adipocyte-specific CD1d deletion decreased the size of the visceral adipose tissue mass and enhanced insulin sensitivity in mice fed a high-fat diet (HFD). Accordingly, NKT cells were less activated, IFN-γ production was significantly reduced, and levels of adiponectin were increased in these animals as compared with control mice on HFD. Importantly, macrophage recruitment into the adipose tissue of adipocyte-specific CD1d-deficient mice was significantly blunted. These findings indicate that interactions between NKT cells and CD1d-expressing adipocytes producing endogenous NKT cell ligands play a critical role in the induction of inflammation and functional modulation of adipose tissue that leads to obesity. PMID:27329323

  16. Purified Betacyanins from Hylocereus undatus Peel Ameliorate Obesity and Insulin Resistance in High-Fat-Diet-Fed Mice.

    PubMed

    Song, Haizhao; Chu, Qiang; Xu, Dongdong; Xu, Yang; Zheng, Xiaodong

    2016-01-13

    Natural bioactive compounds in food have been shown to be beneficial in preventing the development of obesity, diabetes, and other metabolic diseases. Increasing evidence indicates that betacyanins possess free-radical-scavenging and antioxidant activities, suggesting their beneficial effects on metabolic disorders. The main objective of this study was to isolate and identify the betaycanins from Hylocereus undatus (white-fleshed pitaya) peel and evaluate their ability to ameliorate obesity, insulin resistance, and hepatic steatosis in high-fat-diet (HFD)-induced obese mice. The purified pitaya peel betacyanins (PPBNs) were identified by liquid chromatography/tandem mass spectrometry (LC/MS/MS), and the male C57BL/6 mice were fed a low-fat diet, HFD, or HFD supplemented with PPBNs for 14 weeks. Our results showed that the white-fleshed pitaya peel contains 14 kinds of betacyanins and dietary PPBNs reduced HFD-induced body weight gain and ameliorated adipose tissue hypertrophy, hepatosteatosis, glucose intolerance, and insulin resistance. Moreover, the hepatic gene expression analysis indicated that PPBN supplementation increased the expression levels of lipid-metabolism-related genes (AdipoR2, Cpt1a, Cpt1b, Acox1, PPARγ, Insig1, and Insig2) and FGF21-related genes (β-Klotho and FGFR1/2) but decreased the expression level of Fads2, Fas, and FGF21, suggesting that the protective effect of PPBNs might be associated with the induced fatty acid oxidation, decreased fatty acid biosynthesis, and alleviated FGF21 resistance. PMID:26653843

  17. Nicotinic Acid Accelerates HDL Cholesteryl Ester Turnover in Obese Insulin-Resistant Dogs

    PubMed Central

    Le Bloc'h, Jérôme; Leray, Véronique; Nazih, Hassan; Gauthier, Olivier; Serisier, Samuel; Magot, Thierry; Krempf, Michel; Nguyen, Patrick; Ouguerram, Khadija

    2015-01-01

    Aim Nicotinic acid (NA) treatment decreases plasma triglycerides and increases HDL cholesterol, but the mechanisms involved in these change are not fully understood. A reduction in cholesteryl ester transfer protein (CETP) activity has been advanced to explain most lipid-modulating effects of NA. However, due to the central role of CETP in reverse cholesterol transport in humans, other effects of NA may have been hidden. As dogs have no CETP activity, we conducted this study to examine the specific effects of extended-release niacin (NA) on lipids and high-density lipoprotein (HDL) cholesteryl ester (CE) turnover in obese Insulin-Resistant dogs with increase plasma triglycerides. Methods HDL kinetics were assessed in fasting dogs before and four weeks after NA treatment through endogenous labeling of cholesterol and apolipoprotein AI by simultaneous infusion of [1,2 13C2] acetate and [5,5,5 2H3] leucine for 8 h. Kinetic data were analyzed by compartmental modeling. In vitro cell cholesterol efflux of serum from NA-treated dogs was also measured. Results NA reduced plasma total cholesterol, low-density lipoprotein cholesterol, HDL cholesterol, triglycerides (TG), and very-low-density lipoprotein TG concentrations (p < 0.05). The kinetic study also showed a higher cholesterol esterification rate (p < 0.05). HDL-CE turnover was accelerated (p < 0.05) via HDL removal through endocytosis and selective CE uptake (p < 0.05). We measured an elevated in vitro cell cholesterol efflux (p < 0.05) with NA treatment in accordance with a higher cholesterol esterification. Conclusion NA decreased HDL cholesterol but promoted cholesterol efflux and esterification, leading to improved reverse cholesterol transport. These results highlight the CETP-independent effects of NA in changes of plasma lipid profile. PMID:26366727

  18. Acute High-Intensity Interval Exercise-Induced Redox Signaling Is Associated with Enhanced Insulin Sensitivity in Obese Middle-Aged Men

    PubMed Central

    Parker, Lewan; Stepto, Nigel K.; Shaw, Christopher S.; Serpiello, Fabio R.; Anderson, Mitchell; Hare, David L.; Levinger, Itamar

    2016-01-01

    Background: Obesity and aging are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK), and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE) on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men. Methods: Participants completed a 2 h hyperinsulinaemic-euglycaemic clamp at rest, and 60 min after HIIE (4 × 4 mins at 95% HRpeak; 2 min recovery periods), separated by 1–3 weeks. Results: Irrespective of exercise-induced changes to redox status, insulin stimulation both at rest and after HIIE similarly increased plasma superoxide dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling pathways of p38 MAPK, NF-κB p65, and JNK, and the distal insulin signaling protein AS160Ser588, were activated with insulin stimulation at rest and to a greater extent with insulin stimulation after a prior bout of HIIE. Higher insulin sensitivity after HIIE was associated with higher insulin-stimulated SOD activity, JNK, p38 MAPK and NF-κB phosphorylation