(07-03-09) Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction.

Kirk E, Reeds DN, Finck BN, Mayurranjan MS, Klein S.
Center for Human Nutrition and Division of Geriatrics and Nutritional Science Washington University School of Medicine, St. Louis, MO.

BACKGROUND AND AIMS:: We determined the effects of acute and chronic calorie restriction with either a low-fat, high-carbohydrate diet or a low-carbohydrate diet on hepatic and skeletal muscle insulin sensitivity. METHODS:: Twenty-two obese subjects (body-mass index, 36.5+/-0.8kg/m2) were randomized to a high-carbohydrate (>180g/d) or low-carbohydrate (<60g/d) energy-deficit diet. A euglycemic-hyperinsulinemic clamp, muscle biopsies, and magnetic resonance spectroscopy were used to determine insulin action, cellular insulin signaling and intrahepatic triglyceride content before, after 48 h, and after ?11 wks (7% weight loss) of diet therapy. RESULTS:: At 48 h, intrahepatic triglyceride content decreased more in the low-carbohydrate than the high-carbohydrate diet group (29.6+/-4.8% vs. 8.9+/-1.4%; P<0.05), but was similar in both groups after 7% weight loss (low-carbohydrate diet, 38.0+/-4.5% vs. high-carbohydrate diet, 44.5(13.5%). Basal glucose production rate decreased more in the low-carbohydrate than the high-carbohydrate diet group at 48 h (23.4+/-2.2% vs. 7.2+/-1.4%, P<0.05) and after 7% weight loss (20.0+/-2.4% vs. 7.9+/-1.2%, P<0.05). Insulin-mediated glucose uptake did not change at 48 h, but increased similarly in both groups after 7% weight loss (48.4+/-14.3%, P<0.05). In both groups, insulin-stimulated phosphorylation of Jun N-terminal kinase decreased by 29+/-13% and phosphorylation of Akt and insulin receptor substrate -1 increased by 35+/-9% and 36+/-9%, respectively, after 7% weight loss (all p<0.05). CONCLUSION:: Moderate calorie restriction causes temporal changes in liver and skeletal muscle metabolism; 48 h of calorie restriction affects the liver (intrahepatic triglyceride content, hepatic insulin sensitivity, and glucose production), whereas moderate weight loss affects muscle (insulin-mediated glucose uptake and insulin signaling).

Source: Gastroenterology. 2009 Jan 24.

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