PROLONGED INFUSION OF EPINEPHRINE DOWN-REGULATES EXPRESSION OF THE FATTY-ACID SYNTHASE GENE IN ADIPOCYTES

Fatty acid synthase is a key enzyme in the de novo synthesis of fatty acids. Expression of fatty acid synthase mRNA in adipocytes is inhibit ed by beta adrenergic agonists. We wondered if prolonged exposure to h igh concentrations of catecholamines might inhibit expression of the f atty acid synthase gene in fat cells. in this study we investigated th e effects of adrenergic stimulation on the regulation of fatty acid sy nthase in fat cells. Rats were infused continuously with epinephrine ( 60 mu g/kg/hr) or vehicle for 48 h and fat pads were isolated. The inf usion of epinephrine down-regulated expression of the fatty acid synth ase mRNA as well as decreasing enzyme activity. Both epinephrine and i soproterenol inhibited fatty acid synthase mRNA expression when adipoc ytes were activated in vitro. These effects were blocked by the beta a drenergic antagonist propranolol. In contrast, incubation with the ade nosine receptor agonist phenylisopropyladenosine which decreases cAMP accumulation in fat cells, caused an increase in accumulation of fatty acid synthase mRNA. These results indicate that prolonged exposure to catecholamines, acting via beta adrenergic receptors, inhibit express ion of the fatty acid synthase gene possibly by increasing intracellul ar concentrations of cAMP.