Decreased muscle acetyl-coenzyme A carboxylase 2 mRNA and insulin resistance in formerly obese subjects.

by Rosa G, Manco M, Vega N, Greco AV, Castagneto M, Vidal H, Mingrone G.

Department of Internal Medicine, Consiglio Nazionale delle Richerche (CNR) Center, Catholic University of the Sacred Heart, Largo A. Gemelli 8, 00168 Rome, Italy.

OBJECTIVE: A relationship between free fatty acids, intramuscular triglycerides (TG(M)s), and insulin resistance is widely accepted. The intracellular level of malonyl-coenzyme A (CoA) was suggested to be the possible link. Acetyl-CoA carboxylase (ACC) is a key enzyme in fatty acid metabolism, catalyzing the synthesis of malonyl-CoA, a fatty acid acyl-chain elongation unit, from acetyl-CoA. We assessed ACC2 mRNA expression variations in skeletal muscle of subjects who have undergone biliopancreatic diversion (BPD) operation. BPD, in fact inducing a massive lipid malabsorption, leads to a reversion of insulin resistance. RESEARCH METHODS AND PROCEDURES: Twelve obese women (BMI > 40 kg/m(2)) were enrolled in the study. Body composition, euglycemic-hyperinsulinemic clamp, and muscle biopsies for lipid analysis and reverse transcription-competitive polymerase chain reaction were performed before and 3 years after BPD. RESULTS: The average weight loss was around 37%. A significant inverse linear relation was observed between glucose uptake and TG(M) (y = -5.62x - 142.82, R(2) = 0.50, p = 0.01). The reduced amount of ACC2 mRNA directly correlated with both TG(M) (y = 2.11x +69.85, R(2) = 0.70, p = 0.01) and fasting insulin (y = 1.49x + 57.17, R(2) = 0.69, p < 0.01) concentrations. DISCUSSION: In conclusion, down-regulation of ACC2 mRNA, induced by the lowering of plasma insulin concentration, is related to improvement of insulin sensitivity. We hypothesize that reduced amount of malonyl-CoA, consequent to reduced ACC2 mRNA, enhancing fatty acid oxidation, causes lowering of the intramyocitic triglyceride depot.