Expression of genes regulating Malonyl-CoA in human skeletal muscle

In humans and animal models, increased intramuscular lipid (IML) stores have been implicated in insulin resistance. Malonyl‐CoA plays a critical role in cellular lipid metabolism both by serving as a precursor in the synthesis of lipids and by inhibiting lipid oxidation. In muscle, Malonyl‐CoA acts primarily as a negative allosteric regulator of carnitine palmitoyl transferase‐1 (CPT1) activity, thereby blocking the transport of long chain fatty acyl CoAs into the mitochondria for oxidation. In muscle, increased malonyl‐CoA, decreased muscle CPT1 activity, and increased IML have all been reported in obesity. In order to determine whether malonyl‐CoA synthesis might be under transcriptional as well as biochemical regulation, we measured mRNA content of several key genes that contribute to the cellular metabolism of malonyl‐CoA in muscle biopsies from lean to morbidly obese subjects. Employing quantitative real‐time PCR, we determined that expression of mitochondrial acetyl‐CoA carboxylase 2 (ACC2) was increased by 50% with obesity (P