Study secretion of adipokines from fat cells.

Abstract

The adipose tissue is not only a store of excess energy, but it is also an endocrine organ secreting a spectrum of peptides and molecules known as adipokines, having diverse biological activities in a wide range physiological systems. Apelin is a novel adipokine with significant involvement in glucose, lipid and cardiovascular homeostasis and is associated to obesity and the metabolic syndrome. Angiotensin II (Ang II), another adkipokine, is the main effector of the renin-angiotensin system (RAS) and is well known for its role in cardiovascular homeostasis, fluid and electrolyte balance. Apelin and Ang II are found to have opposing cardiovascular roles. In addition, apelin signaling might antagonize Ang II effect of increase blood pressure, block Ang II effects in vascular disease by increasing NO production and directly inhibiting Ang II cellular signaling, demonstrating cardioprotective effect. Recently, it was found that blockade of the RAS during adipogenesis increases apelin production in 3T3-L1 adipocytes, but effects of Ang II signaling on apelin secretion in adipocyte are not known. In the present study, we demonstrated that Ang II regulates apelin production in a dose-dependent biphasic manner and mediates differential effect via angiotensin receptor type 1 and type 2 (AT1 and AT2) in 3T3-L1 adipocytes. AT1 receptor stimulates apelin production in a PKC and Ca2+ dependent pathway whereas AT2 receptor suppresses apelin secretion via cAMP and cGMP dependent pathway. We also showed that apelin significantly up-regulates production of its receptors in 3T3-L1 adipocytes and proved the autocrine or paracrine effects it has in adipocytes. These results provide new insights on the interaction between apelin, apelin receptor and Ang II.