Acetyl CoA carboxylase (ACC) is a key enzyme in energy balance. It controls the synthesis of malonyl-CoA, an allosteric inhibitor of carnitine palmitoyltransferase-1 (CPT-I). CPT-I is the gatekeeper of free fatty acid (FFA) oxidation. To test the hypothesis that both enzymes play critical roles in regulation of FFA partitioning in adipocytes, we compared enzyme mRNA expression and specific activity from fed, fasted, and diabetic rats. Direct effects of nutritional state, insulin, and FFAs on CPT-I and ACC mRNA expression were assessed in adipocytes, liver, and cultured adipose tissue explants. We also determined FFA partitioning in adipocytes from donors exposed to different nutritional conditions. CPT-I mRNA and activity decreased in adipocytes but increased in liver in response to fasting. ACC mRNA and activity decreased in both adipocytes and liver during fasting. These changes were not caused directly by fasting-associated changes in plasma insulin and FFA concentrations because insulin suppressed CPT-I mRNA and did not affect ACC mRNA in vitro, whereas exogenous oleate had no effect on either. Despite the decrease in adipocyte CPT-I mRNA and specific activity, CO(2) production from endogenous FFAs increased, suggesting increased FFA transport through CPT-I for beta-oxidation. Stimulation of FFA transport through CPT-I occurs in both tissues, but CPT-I mRNA and specific activity correlate with FFA transport in liver and not in adipocytes. We conclude that the mechanism responsible for increasing FFA oxidation in adipose tissue during fasting involves mainly allosteric regulation, whereas altered gene expression may play a central role in the liver.
