Skeletal Muscle Lipogenic Protein Expression Is Not Different between Lean and Obese Individuals: A Potential Factor in Ceramide Accumulation

Context: Skeletal muscle lipid content is increased in obesity. Recent evidence suggests that fatty acid (FA) storage as triacylglycerol (TAG) represents a metabolically safe pool compared to the more bioactive diacylglycerol (DAG) and ceramide. Objective/Design: The purpose of this study was to compare the expression of lipogenic proteins and ceramide and DAG content in skeletal muscle of lean and obese humans. We hypothesized that lipogenic protein expression would be increased in obese to facilitate the storage of excess FA as TAG. Participants: Eighteen lean (BMI <= 26 kg/m(2)) and 15 obese (BMI > 29 kg/m(2)) women participated in this study. Results: There was no difference in the expression of any lipogenic (stearoyl-CoA desaturase-1, stearoyl retinol binding protein-1c, mitochondrial glycerol-3-phosphate acyltransferase, diacylglycerol acyltransferase-1) or sphingolipid proteins measured between lean and obese humans. Total ceramide was increased in muscle from obese humans (lean vs. obese, 529.4 +/- 54.8 vs. 672.4 +/- 57.4 nmol/g; P < 0.05), but there was no difference in total DAG content (lean vs. obese, 2244.1 +/- 278.2 vs. 1941.4 +/- 165.0 nmol/g). Content of protein phosphatase 2A, a ceramide target, was increased in muscle of obese humans (P < 0.05). Conclusions: We propose that in muscle of obese humans there is an insufficient lipogenic response to the lipid oversupply, allowing more FA to be stored as reactive lipid species, particularly ceramide, potentially contributing to subsequent metabolic complications. (J Clin Endocrinol Metab 94: 5053-5061, 2009)