Dual Effects of Pituitary Adenylate Cyclase-Activating Polypeptide and Isoproterenol on Lipid Metabolism and Signaling in Primary Rat Adipocytes

Abstract

Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide that exerts its effects throughout the body by elevating the intracellular amounts of cAMP. In adipocytes, an increased amount of cAMP is associated with increased lipolysis. In this work we evaluated the effects of PACAP38 on triglycéride metabolism in primary rat adipocytes. Stimulation of adipocytes with PACAP (0.1-100 nM) resulted in stimulation of lipolysis to the same extent as isoproterenol. Lipolysis was blocked by 25 μM of the protein kinase A inhibitor H-89 and potentiated in the presence of 10 μM OPC3911, a phosphodiesterase 3 inhibitor. In addition, PACAP38 induced activation of protein kinase A. Insulin efficiently inhibited PACAP38-induced lipolysis in a phosphatidyl inositol 3-kinase and phosphodiesterase 3-dependent manner. Interestingly, we also found that PACAP38, as well as isoproterenol, induced potentiation of lipogenesis in the presence of insulin. These results show that PACAP38 and isoproterenol mediate catabolic as well as anabolic effects in adipocytes, depending on the concentration of insulin present. We speculate that in the early postprandial state and during fasting, when insulin levels are low, PACAP and β-adrenergic catecholamines induce lipolysis, whereas when higher levels of insulin are present, these agents potentiate the anabolic effect of insulin, i.e. storage of triglycerides.