title: Stimulatory and Inhibitory regulation of lipolysis by the NPR-A/cGMP/PKG and NPR-C/G(i) pathways in rat cultured adipocytes.
abstract: 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 PPARgamma, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hypertension and Cardiorenal Medicine, Dokkyo Medical University, Mibu, Tochigi 321-0293, Japan. nishikim@dokkyomed.ac.jp
authors.forename: Toshio
authors.initials: T
authors.lastname: Nishikimi
authors.forename: Chikako
authors.initials: C
authors.lastname: Iemura-Inaba
authors.forename: Kazumi
authors.initials: K
authors.lastname: Akimoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Shogo
authors.initials: S
authors.lastname: Koshikawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsuoka
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000502:physiology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D008066:Lipolysis / Q000502:physiology*; D020033:Protein Isoforms / Q000378:metabolism*; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D020033:Protein Isoforms; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D017869:Cyclic GMP-Dependent Protein Kinases; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP