Stimulatory and Inhibitory regulation of lipolysis by the NPR-A/cGMP/PKG and NPR-C/Gi pathways in rat cultured adipocytes

Objective: Recent studies have suggested the abundant expression of natriuretic peptide receptor in adipose tissue. This study was designed to investigate the levels of natriuretic receptor-A (NPR-A) and NPR-C gene expression during the process of preadipocyte differentiation and its role in adipogenesis and lipid metabolism. Methods: We measured mRNA levels of NPR-A and NPR-C during the process of rat preadipocyte differentiation in vitro. We also measured the effects of ANP and C-ANP, a ligand for NPR-C, on preadipocyte differentiation. In addition, we assessed the effects of ANP and C-ANP on lipolysis and the cellular mechanism. Results: The mRNA levels of NPR-A and NPR-C on day 3, 6, 10 are (-26%, + 226%),(+6%, + 568%), and (+207%. + 3232%) respectively as compared with day 1. ANP (10(-7) M) and 8-bromo-cGMP (10(-4) M) significantly increased Oil Red positive area and cell number of matured-adipocytes. ANP and 8-bromo-cGMP also increased the mRNA levels of adipocyte-related genes such as PPAR gamma, leptin, and adiponectin on day 3, whereas C-ANP did not change these parameters. ANP (10(-9)-10(-6) M) increased intracellular cGMP levels and promoted lipolysis in adipocytes and the effects were abolished by HS-142-1, and KT5823. Conversely C-ANP (10(-6) M) decreased intracellular cAMP levels and lipolysis and its effect was inhibited by PTX. Conclusion: Results suggest that ANP may promote adipocyte differentiation and lipolysis via the NPR-A/cGMP/PKG pathway. Direct action of ANP via NPR-C in adipogenesis may be either absent or barely present, but ANP may play a counter regulatory role in lipolysis via NPR-C/Gi pathway. (C) 2008 Elsevier B.V. All rights reserved.