Control of Fatty Acid Synthesis in White Adipose Tissue by Insulin: Coordination Between the Mitochondrial Citrate Transporter and Pyruvate Dehydrogenase

Abstract

The transport of citrate out of adipose tissue mitochondria is inhibited by palmitoyl-CoA. This inhibition varied inversely with the concentration of extramitochondrial exchanging anion.When adipose tissue is incubated in vitro, the rate of citrate output into the medium was increased by the addition of insulin. The tissue citrate content did not change significantly. Norepinephrine caused an initial decrease in the rate of citrate output (2.5 min). The tissue citrate content was approximately twofold higher at this time.When rats were fasted for 36 h, less than 40% of adipose tissue pyruvate dehydrogenase was in the active form. Optimal interconversion to the active form was achieved by preincubation with 4 mM Mg2+ in the absence of added Ca2+ (endogenous Ca2+ was approximately 25 μM). Citrate addition to the preincubation medium decreased this activation of pyruvate dehydrogenase. The inhibition induced by citrate correlated best with the concentration of 'free' citrate when the 'free' Mg2+ concentration was sufficient to cause near-maximal activation of pyruvate dehydrogenase.A hypothesis regarding the coordination of regulation of pyruvate conversion to fatty acids is formulated based on these findings.