Decreased Muscle Acetyl-Coenzyme A Carboxylase 2 mRNA and Insulin Resistance in Formerly Obese Subjects

Objective:A relationship between free fatty acids, intramuscular triglycerides (TGMs), 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/m2) 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 TGM (y = −5.62x − 142.82, R2 = 0.50, p = 0.01). The reduced amount of ACC2 mRNA directly correlated with both TGM (y = 2.11x +69.85, R2 = 0.70, p = 0.01) and fasting insulin (y = 1.49x + 57.17, R2 = 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.