Regulation of lipogenic enzyme and phosphoenolpyruvate carboxykinase gene expression in cultured white adipose tissue

Abstract

In cultured adipose tissue of suckling rats, glucose alone is able to induce the appearance of fatty-acid synthase and acetyl-CoA carboxylase mRNA by a mechanism involving glucose-6-phosphate accumulation; insulin alone has no effect but potentiates the effect of glucose. In the present study, we have analysed in cultured adipose tissue the effects of other hormones on the expression of these enzymes as well as on phosphoenolpyruvate carboxykinase. Triiodothyronine has only a marginal effect on fatty-acid synthase expression, in the absence or presence of glucose and insulin. A synthetic glucocorticoid, dexamethasone, opposes the inductive effect of glucose and insulin on fatty-acid synthase expression but increases the expression of phosphoenolpyruvate carboxykinase. A beta-agonist, isoproterenol totally inhibits the inductive effect of glucose and insulin on acetyl-CoA carboxylase and fatty-acid synthase expression whereas it increases the expression of phosphoenolpyruvate carboxykinase. Similarly, glucagon and cAMP have antagonistic effects on glucose and insulin-induced fatty-acid synthase expression. These inhibitory effects cannot be explained only by a reduction in glucose-6-phosphate concentration. We conclude that, in adipose tissue, dexamethasone and cAMP-generating hormones are negative regulators of lipogenic enzyme expression. Finally, the regulation of phosphoenolpyruvate carboxykinase expression in adipose tissue is similar to that found in the liver, i.e. inhibition by insulin and glucose and activation by glucocorticoids and cAMP.