Weight loss reduces liver fat and improves hepatic and skeletal muscle insulin sensitivity in obese adolescents.

Obesity in adolescents is associated with metabolic risk factors for type 2 diabetes, particularly insulin resistance and excessive accumulation of intrahepatic triglyceride (IHTG). The purpose of this study was to evaluate the effect of moderate weight loss on IHTG content and insulin sensitivity in obese adolescents who had normal oral glucose tolerance. Insulin sensitivity, assessed by using the hyperinsulinemic-euglycemic clamp technique in conjunction with stable isotopically labeled tracer infusion, and IHTG content, assessed by using magnetic resonance spectroscopy, were evaluated in eight obese adolescents (BMI >or=95th percentile for age and sex; age 15.3 +/- 0.6 years) before and after moderate diet-induced weight loss (8.2 +/- 2.0% of initial body weight). Weight loss caused a 61.6 +/- 8.5% decrease in IHTG content (P = 0.01), and improved both hepatic (56 +/- 18% increase in hepatic insulin sensitivity index, P = 0.01) and skeletal muscle (97 +/- 45% increase in insulin-mediated glucose disposal, P = 0.01) insulin sensitivity. Moderate diet-induced weight loss decreases IHTG content and improves insulin sensitivity in the liver and skeletal muscle in obese adolescents who have normal glucose tolerance. These results support the benefits of weight loss therapy in obese adolescents who do not have evidence of obesity-related metabolic complications during a standard medical evaluation.

Alterations in fatty acid kinetics in obese adolescents with increased intrahepatic triglyceride content.

OBJECTIVE: It has been hypothesized that excessive fatty acid availability contributes to steatosis and the metabolic abnormalities associated with nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to evaluate whether adipose tissue lipolytic activity and the rate of fatty acid release into plasma are increased in obese adolescents with NAFLD. METHODS: Palmitate kinetics were determined in obese adolescents with normal (n = 9; BMI = 37 +/- 2 kg/m(2); intrahepatic triglyceride (IHTG) or= 10% of liver volume) IHTG content during the basal state (postabsorptive condition) and during physiological hyperinsulinemia (postprandial condition). Both groups were matched on body weight, BMI, percent body fat, age, sex, and Tanner stage. The hyperinsulinemic-euglycemic clamp procedure, in conjunction with a deuterated palmitate tracer infusion, was used to determine free-fatty acid (FFA) kinetics, and magnetic resonance spectroscopy was used to determine IHTG content. RESULTS: The rate of whole-body palmitate release into plasma was greater in subjects with NAFLD than those with normal IHTG content during basal conditions, (87 +/- 7 vs. 127 +/- 13 micromol/min; P < 0.01) and during physiological hyperinsulinemia, (24 +/- 2 vs. 44 +/- 8 micromol/min; P < 0.01). DISCUSSION: These results demonstrate that adipose tissue lipolytic activity is increased in obese adolescents with NAFLD and results in an increase in the rate of fatty acid release into plasma throughout the day. This continual excess in fatty acid flux supports the hypothesis that adipose insulin resistance is involved in the pathogenesis of steatosis and contributes to the metabolic complications associated with NAFLD.

Nonalcoholic fatty liver disease is associated with hepatic and skeletal muscle insulin resistance in overweight adolescents.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and insulin resistance are common in overweight adolescents. OBJECTIVE: The purpose of this study was to determine the relation between NAFLD and insulin sensitivity in liver and skeletal muscle by studying overweight adolescents with a normal or high intrahepatic triglyceride (IHTG) content, who were matched for age, sex, body mass index (BMI; in kg/m(2)), and Tanner stage. DESIGN: Stable-isotope-labeled tracer infusion and the hyperinsulinemic-euglycemic clamp procedure were used to assess skeletal muscle and hepatic insulin sensitivity, and magnetic resonance spectroscopy was used to assess the IHTG content in 10 overweight (BMI = 35.9 +/- 1.3) adolescents with NAFLD (IHTG = 28.4 +/- 3.4%) and 10 overweight (BMI = 36.6 +/- 1.5) adolescents with a normal IHTG content (3.3 +/- 0.5%). RESULTS: The baseline plasma glucose concentration and the rate of appearance of glucose in plasma were the same in subjects with a normal (87.1 +/- 1.2 mg/dL, 16.2 +/- 1.1 micromol . kg fat-free mass(-1) . min(-1)) or high (89.2 +/- 2.5 mg/dL, 16.3 +/- 1.2 micromol . kg fat-free mass(-1) . min(-1)) IHTG content. However, compared with subjects who had a normal IHTG content, subjects with NAFLD had a lower hepatic insulin sensitivity index, based on baseline glucose kinetics and insulin concentrations (4.0 +/- 0.5 compared with 2.4 +/- 0.4; P < 0.05) and an impaired increase in glucose uptake during insulin infusion (169 +/- 28.1% compared with 67 +/- 9.6% above baseline; P < 0.01). In addition, the plasma triglyceride concentration was greater and the plasma HDL-cholesterol concentration was lower in subjects with NAFLD than in those with a normal IHTG content. CONCLUSION: An elevated IHTG content in overweight adolescents is associated with dyslipidemia and with insulin-resistant glucose metabolism in both liver and skeletal muscle.