PT - JOURNAL ARTICLE AU - Houmard, Joseph A. AU - Tanner, Charles J. AU - Yu, Chunli AU - Cunningham, Paul G. AU - Pories, Walter J. AU - MacDonald, Kenneth G. AU - Shulman, Gerald I. TI - Effect of Weight Loss on Insulin Sensitivity and Intramuscular Long-Chain Fatty Acyl-CoAs in Morbidly Obese Subjects AID - 10.2337/diabetes.51.10.2959 DP - 2002 Oct 01 TA - Diabetes PG - 2959--2963 VI - 51 IP - 10 4099 - http://diabetes.diabetesjournals.org/content/51/10/2959.short 4100 - http://diabetes.diabetesjournals.org/content/51/10/2959.full SO - Diabetes2002 Oct 01; 51 AB - Increases in intramyocellular long-chain fatty acyl-CoAs (LCACoA) have been implicated in the pathogenesis of insulin resistance in skeletal muscle. To test this hypothesis, we measured muscle (vastus lateralis) LCACoA content and insulin action in morbidly obese patients (n = 11) before and after weight loss (gastric bypass surgery). The intervention produced significant weight loss (142.3 ± 6.8 vs. 79.6 ± 4.1 kg for before versus after surgery, respectively). Fasting insulin decreased by ∼ 84% (23.3 ± 3.8 vs. 3.8 ± 0.5 mU/ml), and insulin sensitivity, as determined by minimal model, increased by ∼360% (1.2 ± 0.3 vs. 4.1 ± 0.5 min−1 · [μ U/kg−1]) indicating enhanced insulin action. Muscle palmityl CoA (16:0; 0.54 ± 0.08 vs. 0.35 ± 0.04 nmol/g wet wt) concentration decreased by ∼35% (P < 0.05) with weight loss, whereas stearate CoA (18:0; −17%; 0.65 ± 0.05 vs. 0.54 ± 0.03 nmol/g wet wt) and linoleate CoA (18:2; −30%; 2.47 ± 0.27 vs. 1.66 ± 0.19 nmol/g wet wt) were also reduced (P < 0.05). There were no statistically significant declines in muscle palmitoleate CoA (16:1), oleate CoA (18:1), or total LCACoA content. These data suggest that a reduction in intramuscular LCACoA content may be responsible, at least in part, for the enhanced insulin action observed with weight loss in obese individuals.