Influence of Gender, Obesity, and Muscle Lipase Activity on Intramyocellular Lipids in Sedentary Individuals

Context: Obesity and type 2 diabetes are associated with elevated intramyocellular lipids (IMCLs) and insulin resistance. Objective: We tested the hypothesis that skeletal muscle lipases activity could influence IMCL content (including diacylglycerol and ceramides). Design and Patients: The present study included 48 subjects with a wide range of age (19-68 yr) and body mass index (20-45 kg/m(2)) who underwent skeletal muscle biopsy, dual-energy x-ray absorptiometry and a hyperinsulinemic euglycemic clamp. Main Outcome Measures: Insulin sensitivity by hyperinsulinemic clamp, and intramyocellular triacylglycerol (IMTG), diacylglycerol (DAG), and ceramides content, and triacylglycerol and diacylglycerol hydrolase activities were measured in biopsies of vastus lateralis. IMCL was measured by H-1-magnetic resonance spectroscopy in a subgroup of 25 subjects. Multivariate regression analyses were performed to identify the main predictors of IMCL. Results: Body fat was the main predictor of IMTG independently of the method and the type of muscle; IMTG concentration was higher in females vs. males and obese vs. nonobese subjects. Muscle DAG and ceramides concentrations were elevated in obese and type 2 diabetic subjects and were not related to body fat and fasting free fatty acids, whereas a direct association with the ratio of diacylglycerol hydrolase to triacylglycerol hydrolase activity (an index of incomplete triacylglycerol hydrolysis) was observed, which explained 54 and 38% of the variance in DAG and ceramides (P < 0.001), respectively. DAG content was the main determinant of insulin resistance. Conclusions: These data suggest that intramyocellular DAG is an independent predictor of insulin resistance in humans and that its levels correlate with lipolytic enzymes activity in skeletal muscle but not with markers of adiposity. (J Clin Endocrinol Metab 94: 3440-3447, 2009)