Metabolic consequences of hepatic steatosis in overweight and obese adolescents

OBJECTIVE - To test the hypothesis that hepatic steatosis is associated with risk factors for type 2 diabetes in overweight and obese youth, mediated by cardiorespiratory fitness. RESEARCH DESIGN AND METHODS - This was a cross-sectional study comparing insulin sensitivity between 30 overweight and obese adolescents with hepatic steatosis, 68 overweight and obese adolescents without hepatic steatosis, and 11 healthy weight adolescents without hepatic steatosis. Cardiorespiratory fitness was determined by a graded maximal exercise test on a cycle ergometer. Secondary outcomes included presence of metabolic syndrome and glucose response to a 75-g oral glucose challenge. RESULTS - The presence of hepatic steatosis was associated with 55%lower insulin sensitivity (P = 0.02) and a twofold greater prevalence of metabolic syndrome (P = 0.001). Differences in insulin sensitivity (3.5 vs. 4.5 mU \ub7 kg -1 \ub7 min -1, P = 0.03), prevalence of metabolic syndrome (48 vs. 20%, P = 0.03), and glucose area under the curve (816 vs. 710, P = 0.04) remained between groups after matching for age, sex, and visceral fat. The association between hepatic steatosis and insulin sensitivity (\u3b2 = -0.24, t = -2.29, P < 0.025), metabolic syndrome (\u3b2 = -0.54, t = -5.8, P < 0.001), and glucose area under the curve (\u3b2 = 0.33, t = 3.3, P < 0.001) was independent of visceral and whole-body adiposity. Cardiorespiratory fitness was not associated with hepatic steatosis, insulin sensitivity, or presence of metabolic syndrome. CONCLUSIONS - Hepatic steatosis is associated with type 2 diabetes risk factors independent of cardiorespiratory fitness, whole-body adiposity, and visceral fat mass. \ua9 2012 by the American Diabetes Association.Peer reviewed: YesNRC publication: Ye

Cardiorespiratory fitness and adiposity in metabolically healthy overweight and obese youth

OBJECTIVE: Controversy exists surrounding the contribution of fitness and adiposity as determinants of the Metabolically Healthy Overweight (MHO) phenotype in youth. This study investigated the independent contribution of cardiorespiratory fitness and adiposity to the MHO phenotype among overweight and obese youth. METHODS: This cross-sectional study included 108 overweight and obese youth classified as MHO (no cardiometabolic risk factors) or non-MHO ($1 cardiometabolic risk factor), based on age- and genderspecific cut-points for fasting glucose, triglycerides, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, and hepatic steatosis. RESULTS: Twenty-five percent of overweight and obese youth were classified as MHO. This phenotype was associated with lower BMI z-score (BMI z-score: 1.8 \ub1 0.3 vs 2.1 \ub1 0.4, P = .02) and waist circumference (99.7 \ub1 13.2 vs 106.1 \ub1 13.7 cm, P = .04) compared with non-MHO youth. When matched for fitness level and stratified by BMI z-score (1.6 \ub1 0.3 vs 2.4 \ub1 0.2), the prevalence of MHO was fourfold higher in the low BMI z-score group (27% vs 7%; P = .03). Multiple logistic regression analyses revealed that the best predictor of MHO was the absence of hepatic steatosis even after adjusting for waist circumference (odds ratio 0.57, 95% confidence interval 0.40- 0.80) or BMI z-score (odds ratio 0.59, 95% confidence interval 0.43- 0.80). CONCLUSIONS: The MHO phenotype was present in 25% of overweight and obese youth and is strongly associated with lower levels of adiposity, and the absence of hepatic steatosis, but not with cardiorespiratory fitness. Pediatrics 2013;132:e85-e92. Copyright \ua9 2013 by the American Academy of Pediatrics.Peer reviewed: YesNRC publication: Ye

Gender-dependent effects of high-fat lard diet on cardiac function in C57Bl/6J mice.

Item does not contain fulltextIncreased availability of fatty acids released from insulin-resistant adipose tissue may lead to excess fatty acid uptake in nonadipose organs, including the heart. Accumulation of toxic fatty acid intermediates may affect cardiac function. Our aim was to identify to which extent high-fat diet feeding leads to alterations in cardiac function and whether this depends on gender and (or) duration of high-fat diet feeding. Male and female C57Bl/6J mice (n = 8 per group) of 12 to 16 weeks old were fed a low-fat (10% energy) or high-fat (45% energy) lard diet for 6 or 12 weeks. Plasma lipid levels, echocardiography, and left ventricular pressure-volume relationships were obtained at 2, 1, and 0 weeks before termination, respectively. In both male and female mice, the high-fat diet increased body weight and plasma lipid content. At 10 weeks, significant increases were observed for plasma total cholesterol (males: +44%; females: +86%), phospholipids (+16% and +34%), and triglycerides (+27% and +53%) (all p < 0.001). In male mice, but not in female mice, the high-fat diet significantly affected cardiac function at 12 weeks with increased end-systolic volume (25.4 +/- 6.2 vs. 17.0 +/- 6.7 microL, p < 0.05), increased end-systolic pressure (72.1 +/- 6.9 vs. 63.6 +/- 6.9 mm Hg, p < 0.01), and decreased ejection fraction (61.2% +/- 4.5% vs. 68.1% +/- 3.7%, p < 0.01), indicating reduced systolic function. Multiple linear regression analysis indicated a significant diet-gender interaction for end-systolic volume and ejection fraction. In conclusion, high-fat diet feeding increased body weight and plasma lipid levels in male and in female mice, but resulted in impairment of cardiac function only in males.1 april 201