Skeletal-Muscle Triglycerides, Diacylglycerols, and Ceramides in Insulin Resistance: Another Paradox in Endurance-Trained Athletes?

FRANCESCA AMATI, JOHN J. DUBÉ, ELVIS ALVAREZ CARNERO, MARTIN M. EDREIRA, PETER CHOMENTOWSKI, PAUL M. COEN, GALEN E. SWITZER, PERRY E. BICKEL, MAJA STEFANOVIC-RACIC, FREDERICO G.S. TOLEDO, AND BRET H. GOODPASTER

DIABETES

AMER DIABETES ASSOC

Año: 2011 p. 1 - 10

0012-1797

OBJECTIVE—Chronic exercise and obesity both increase intramusculartriglycerides (IMTGs) despite having opposing effectson insulin sensitivity. We hypothesized that chronically exercisetrainedmuscle would be characterized by lower skeletal-musclediacylglycerols (DAGs) and ceramides despite higher IMTGs andwould account for its higher insulin sensitivity. We also hypothesizedthat the expression of key skeletal-muscle proteins involved inlipid-droplet hydrolysis, DAG formation, and fatty-acid partitioningand oxidation would be associated with the lipotoxic phenotype.RESEARCH DESIGN AND METHODS—A total of 14 normalweight,endurance–trained athletes (NWA group) and 7 normalweightsedentary (NWS group) and 21 obese sedentary (OBS group)volunteers were studied. Insulin sensitivity was assessed by glucoseclamps. Intramyocellular triglycerides (IMTGs), DAGs, ceramides,and protein expression were measured in muscle biopsies.RESULTS—DAG content in the NWA group was approximatelytwofold higher than in the OBS group and ~50% higher than in theNWS group, corresponding to higher insulin sensitivity. Whilecertain DAG moieties clearly were associated with better insulinsensitivity, other species were not. Ceramide content was higherin insulin-resistant obese muscle. The expression of OXPAT/perilipin-5, adipose triglyceride lipase, and stearoyl-CoA desaturaseprotein was higher in the NWA group, corresponding to a highermitochondrial content, proportion of type 1 myocytes, IMTGs,DAGs, and insulin sensitivity.CONCLUSIONS—Total myocellular DAGs were markedly higherin highly trained athletes, corresponding with higher insulin sensitivity,and suggest a more complex role for DAGs in insulin action.Our data also provide additional evidence in humans linkingceramides to insulin resistance. Finally, this study provides novelevidence supporting a role for specific skeletal-muscle proteinsinvolved in intramyocellular lipids, mitochondrial oxidative capacity,and insulin resistance.