Comparing Liver And Skeletal Muscle Sensitivity In Response To Acute And Chronic Calorie Restriction

Abstract

PURPOSE: We determined the effects of acute and chronic calorie restriction on hepatic and skeletal muscle insulin sensitivity. METHODS: Twenty-three obese subjects (body-mass index, 36.3±0.7kg/m2) followed an 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 (-16.6±2.3%, p<0.001) and 7% weight loss (-40.7 ± 6.2%; p<0.001) 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 change at 48-h (-5.2±12.8%, p>0.05) but did significantly increase at 7% weight loss (26.1 ± 4.3%, p<0.05). Insulin-stimulated phosphorylation of Jun N-terminal kinase did not change at 48-h (-0.2 ± 16.2%, p>0.05) but did significantly decrease at 7% weight loss (-29.9 ± 12.6, p<0.05) and phosphorylation of Akt increased by 15.2 ± 14.6% (p>0.05) and 36.2 ± 8.8%,(p<0.05), after 48-h and 7% weight loss, respectively. CONCLUSION: A low 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.