title: Chronic endothelin-1 infusion causes adipocyte hyperplasia in rats.
abstract: OBJECTIVE
  The aim of this study was to investigate the regulatory mechanism of endothelin-1 (ET-1), an endothelium-derived vasoconstrictor, on adipogenesis in vitro and in vivo.
  
  
  METHODS
  3T3-L1 preadipocytes were used to explore the mechanisms mediating ET-1 actions on preadipocyte proliferation and adipocyte differentiation. To investigate the in vivo effect of ET-1, male Sprague-Dawley rats were infused with ET-1 or saline for 4 weeks via intraperitoneally implanted osmotic pumps, and the fat pad weight and adipocyte size of adipose tissues were measured.
  
  
  RESULTS
  ET-1 stimulated preadipocyte proliferation and increased the cell number at the mitotic clonal expansion stage of adipocyte differentiation via the endothelin A receptor (ETAR) and activation of the protein kinase C (PKC) pathway. ET-1, via ETAR, inhibited adipocyte differentiation partially through an ERK-dependent pathway. Furthermore, no significant difference in the body weight and fat pad weight was observed in either ET-1- or saline-infused rats. Compared with saline-infused rats, the adipocyte cell number was significantly increased but the adipocyte size was significantly decreased in ET-1-infused rats.
  
  
  CONCLUSIONS
  Chronic ET-1 infusion increased the number of small adipocytes without the change of white adipose tissue mass in rats, which were associated with ET-1-stimulated preadipocyte proliferation, but not ET-1-suppressed adipocyte differentiation.
authors.affiliation: Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chih-Chan
authors.initials: CC
authors.lastname: Lien
authors.affiliation: Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jia-Ling
authors.initials: JL
authors.lastname: Jiang
authors.affiliation: Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Nephrology, Wen-Lin Hemodialysis Unit, Taipei, Taiwan.
authors.forename: Deng-Yuan
authors.initials: DY
authors.lastname: Jian
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Ching-Fai
authors.initials: CF
authors.lastname: Kwok
authors.affiliation: Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Low-Tone
authors.initials: LT
authors.lastname: Ho
authors.affiliation: Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Education and Research, Taipei City Hospital, Taipei, Taiwan.
authors.forename: Chi-Chang
authors.initials: CC
authors.lastname: Juan
mesh_terms: D041721:3T3-L1 Cells / Q000187:drug effects; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology*; D006965:Hyperplasia / Q000209:etiology* / Q000378:metabolism; D008297:Male; D051379:Mice; D009765:Obesity / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000187:drug effects* / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D044022:Receptor, Endothelin A