PYRUVATE STIMULATES HORMONAL INDUCTION OF LIPOGENIC ENZYMES IN PRIMARY CULTURED RAT HEPATOCYTES

Hormonal inductions of lipogenic enzyme activities (fatty acid synthet ase, malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PD) and A TP-citrate lyase) were studied in primary cultured rat hepatocytes. In sulin, triiodothyronine and dexamethasone markedly stimulated the indu ctions of the enzymes (particularly G6PD and ME) in the presence of py ruvate. Lactate also induced their activities. The activities of these enzymes in the presence of appropriate hormone combinations and a sub strate amount of pyruvate were as high as, or higher than those in the liver of rats on high-carbohydrate, low-fat diet. The aldolase and gl ucokinase activities induced by these hormones were not enhanced by th e addition of pyruvate. The induction by pyruvate was inhibited by act inomycin D or cycloheximide. The ATP content of rat hepatocytes was ma intained without increase during culture with pyruvate for 6 days. The se results indicate that the additions of pyruvate, or its metabolites to cultures of isolated hepatocytes have specific effects on the indu ctions of certain hepatic enzymes, possibly acting at the level of tra nscription. Their effects are similar to those of feeding a high-carbo hydrate, low-fat diet to intact animals.