effect of insulin on ketogenesis and fatty acid synthesis in rat hepatocytes incubated with dichloroacetate in parenchymal liver cells isolated from fed rats insulin increased the formation of 14co2 from 114cpyruvate and presumably the flux through pyruvate dehydrogenase by 14 dichloroacetate an activator of the pyruvate dehydrogenase complex stimulated this process by 133 as judged from the conversion of 214cpyruvate to 14co2 the tricarboxylic acid cycle activity was not affected by insulin but it was depressed by dichloroacetate in hepatocytes from fed rats incubated with glucose as the only carbon source dichloroacetate caused a stimulation 31 of fatty acid synthesis measured as 3h incorporation from 3h2o into fatty acid and an increased 134 accumulation of ketone bodies acetoacetate d3hydroxybutyrate dichloroacetate did not affect ketone body formation from 14cpalmitate suggesting that the increased accumulation of ketone bodies resulted from acetylcoa derived from pyruvate insulin stimulated fatty acid synthesis in hepatocytes from fed rats in the combined presence of insulin plus dichloroacetate fatty acid synthesis was more rapid than in the presence of either insulin or dichloroacetate whereas the accumulation of ketone bodies was smaller than in the presence of dichloroacetate alone although pyruvate dehydrogenase activity which is ratelimiting for fatty acid synthesis in hepatocytes from fed rats is stimulated both by insulin and by dichloroacetate the reciprocal changes in fatty acid synthesis and ketone body accumulation brought about by insulin in the presence of dichloroacetate suggest that insulin is also involved in the regulation of fatty acid synthesis at a mitochondrial site after pyruvate dehydrogenase possibly at the partitioning of acetylcoa between citrate and ketone body formation