Sensitivity of lipolysis and lipogenesis to dibutyryl-cAMP and β-adrenergic agonists in swine adipocytes in vitro2

Abstract

The sensitivities of lipolysis and fatty acid synthesis to dibutyryl-cAMP (dbcAMP), epinephrine, ractopamine and clenbuterol were quantified in vitro using porcine adipocytes. Insulin-stimulated lipogenesis showed a biphasic response to dbcAMP, with increased rates at low concentrations and decreased (55%) rates at higher concentrations of dbcAMP. In the absence of insulin, lipogenesis was inhibited 78% by dbcAMP. In the presence of adenosine deaminase or theophylline, all three beta-adrenergic agonists inhibited basal lipogenesis, but only epinephrine and ractopamine inhibited insulin-stimulated lipogenesis. The relationship between suppressed lipogenesis and enhanced lipolysis in response to dbcAMP and the beta-agonists revealed that 1) basal lipogenesis was more sensitive to inhibition than was the stimulation of lipolysis, 2) sensitivity differences were magnified if adenosine deaminase was present and 3) insulin decreased adipocyte sensitivity to the inhibitory effects of dbcAMP and the beta-adrenergic agonists. These results indicate that the relative sensitivities of lipogenesis and lipolysis to beta-adrenergic stimulation can be modified by adenosine and insulin. Furthermore, adenosine and insulin antagonize beta-adrenergic responses, in part, by cAMP-independent mechanisms.