Regulation of lipogenesis in adipose tissue: the significance of the activation of pyruvate dehydrogenase by insulin

Simultaneous measurements were made of lipogenesis and pyruvate dehydrogenase activity in segments of rat epididymal adipose tissue incubated with saturating amounts of U-¹⁴C]glucose and insulin. Glucose was converted to fatty acids at a rate only 64–79% of that permitted by the tissue's content of the active form of pyruvate dehydrogenase (PDH_a). Addition of either of the electron acceptors, phenazine methosulfate (10 μm) or N,N,N′,N′-tetramethyl-p-phenylenediamine (50 μm), increased lipogenesis until it equalled the PDH_a activity of the tissue. Pyruvate release was increased 2-fold or more by the electron acceptors, suggesting that the increase in lipogenesis might have resulted from an increase in the intracellular pyruvate levels such that PDH_a became saturated with substrate. Higher levels of the electron acceptors decreased PDH_a activity, and reduced lipogenesis correspondingly. The data suggest that the maximal rate of lipogenesis in the presence of glucose and insulin is limited by the inability of the tissue to elevate pyruvate levels sufficiently to saturate PDH_a. Although glycerol release was increased by either electron acceptor and insulin partially overcame this effect, the effects of the electron acceptors on PDH_a activity could not be attributed to an increase in lipolysis.