REGULATION OF LIPOGENIC ENZYME GENE-EXPRESSION BY NUTRIENTS AND HORMONES

In vivo and in vitro experiments strongly support the view that marked increases in the levels of mRNA and in the activities of lipogenic en zymes that occur in liver and white adipose tissue of the rat after we aning to a high-carbohydrate diet are dependent on an increase in plas ma glucose and insulin concentrations. An increased glucose metabolism is necessary for the expression of insulin effects on fatty acid synt hase (FAS) and acetyl-CoA carboxylase (ACC) mRNA accumulation in white adipose tissue, as insulin is ineffective in vitro in the absence of glucose. It is suggested that intracellular glucose-6-phosphate could play an important role in the effect of insulin on lipogenic enzyme ge ne expression in white adipose tissue. Other hormones and substrates c ould also play a role in the surge of lipogenesis after weaning. The f all in plasma glucagon after weaning to a high-carbohydrate diet could reinforce the insulin-induced accumulation of FAS and ACC mRNA, as th is hormone inhibits the accumulation of lipogenic enzyme mRNA in liver and white adipose tissue. The decrease in the dietary supply of fat a fter weaning to a high-carbohydrate diet could also potentiate the acc umulation of FAS and ACC mRNA in liver because long-chain polyunsatura ted fatty acids are potent inhibitors of the expression of the genes e ncoding liver lipogenic enzymes. A direct effect of fatty acids on a c is-acting element of the lipogenic enzyme genes could be involved, as the regulatory region of FAS gene contains a polyunsaturated fatty aci d response element that shares some similarity with the peroxisome pro liferator-activated receptor recently described.