Changes In Liver And Skeletal Muscle Sensitivity In Response To Acute And Chronic Calorie Restriction On A Low Carbohydrate Diet

Abstract

PURPOSE: We determined the effects of acute and chronic calorie restriction with a low-carbohydrate diet on hepatic and skeletal muscle insulin sensitivity. METHODS: Twelve obese subjects (body-mass index, 36.1±1.0kg/m2) followed a low-carbohydrate (<60g/d) energy-deficit diet (1,200kcals/day). Magnetic resonance spectroscopy, muscle biopsies, and a euglycemic-hyperinsulinemic clamp were used to determine insulin action, cellular insulin signaling and intrahepatic triglyceride content before, after 48 h, and after ~12 wks (7% weight loss) of diet therapy. RESULTS: Intrahepatic triglyceride content significantly decreased at both 48-h (28.6±3.8%) and 7% weight loss (-38.0 ± 4.5%; p<0.05) compared to baseline. Basal glucose production rate significantly decreased at 48 h (21.8±3.2%, p<0.001) and after 7% weight loss (20.8±3.4%, p<0.001). Insulin- mediated glucose uptake did not significantly increase at 48 h (4.4±12.7%, p>0.05) but did significantly increase at 7% weight loss (35.2 ± 8.4%, p<0.05). Insulin-stimulated phosphorylation of Jun N-terminal kinase decreased by (-15.4 ± 18.1%, p>0.05) and -41.3 ± 19.5, p<0.05) and phosphorylation of Akt increased by 19.2 ± 26.9% (p>0.05) and 36.1 ± 12.4%,(p<0.05), after 48-h and 7% weight loss respectively. CONCLUSIONS: A low carbohydrate calorie diet acutely reduced intrahepatic triglyceride content and improved hepatic insulin sensitivity whereas moderate weight loss is necessary to improve insulin sensitivity in the skeletal muscle.