Skeletal Muscle Fatty Acid Oxidation and Obesity

Abstract

Obesity, which is associated with insulin resistance and diabetes, is increasing at epidemic rates. Skeletal muscle from morbidly obese individuals displays a distinct phenotype that is characterized by decreased fatty acid oxidation (FAO) and increased lipid storage. It is thus important to determine the effect of obesity interventions (i.e. weight loss, exercise) on these defects in obese skeletal muscle. PURPOSE To examine the effect of surgically induced weight loss (via gastric bypass) and aerobic exercise on skeletal muscle lipid metabolism. METHODS Skeletal muscle FAO was assessed using whole muscle homogenates obtained from the vastus lateralis. Rate of 14CO2 production and label incorporation into acid soluble metabolites was determined from incubating homogenates with 1−14C palmitate. Female participants were examined prior to and 1 yr post gastric bypass (post-GOP) surgery (n=2 longitudinally, n=6 cross-sectional), a period when the participants are weight stable. The effect of 10 consecutive days of exercise at 75% VO2peak for 60min/day was examined in formerly morbidly obese, weight matched controls, and lean controls. RESULTS Weight loss (∼100 lbs) had no effect on fatty acid oxidation in skeletal muscle in subjects studied before and after weight loss in both the longitudinal and cross-sectional comparisons. Specifically, the cross sectional comparison of post-GOP subjects to never-morbidly obese weight matched controls demonstrated reduced (∼46%) FAO in post-GOP subjects. Exercise training significantly increased FAO in lean (52.51±10.3 to 73.94±10.7 ηM/g protein/min, 40%), obese (41.96±5.7 to 70.92±6.36) and formerly obese individuals (27.98±5.4 to 79.0±20, 163%). CONCLUSIONS Weight loss has no effect on skeletal muscle FAO which supports the notion that reduced FAO in skeletal muscle contributes to obesity and insulin resistance. Exercise corrects the defect in skeletal muscle FAO observed with obesity.