Prolonged infusion of epinephrine down-regulates expression of the fatty acid synthase gene in adipocytes

Abstract

Fatty acid synthase is a key enzyme in thede novo synthesis of fatty acids. Expression of fatty acid synthase mRNA in adipocytes is inhibited by beta adrenergic agonists. We wondered if prolonged exposure to high concentrations of catecholamines might inhibit expression of the fatty acid synthase gene in fat cells. In this study we investigated the effects of adrenergic stimulation on the regulation of fatty acid synthase in fat cells. Rats were infused continuously with epinephrine (60 μg/kg/hr) or vehicle for 48 h and fat pads were isolated. The infusion of epinephrine down-regulated expression of the fatty acid synthase mRNA as well as decreasing enzyme activity. Both epinephrine and isoproterenol inhibited fatty acid synthase mRNA expression when adipocytes were activatedin vitro. These effects were blocked by the β adrenergic antagonist propranolol. In contrast, incubation with the adenosine receptor agonist phenylisopropyl-adenosine 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 β adrenergic receptors, inhibit expression of the fatty acid synthase gene possibly by increasing intracellular concentrations of cAMP.