title: Adiponectin protects against angiotensin II-induced cardiac fibrosis through activation of PPAR-alpha.
abstract: OBJECTIVE
  Adiponectin is recognized as an antidiabetic, antiatherosclerotic, and anti-inflammatory protein derived from adipocytes. However, the role of adiponectin in cardiac fibrosis remains uncertain. We herein explore the effects of adiponectin on cardiac fibrosis induced by angiotensin II (Ang II).
  
  
  RESULTS
  Wild-type (WT), adiponectin knockout (Adipo-KO), and PPAR-alpha knockout (PPAR-alpha-KO) mice were infused with Ang II at 1.2 mg/kg/d. Severe cardiac fibrosis and left ventricular dysfunction were observed in Ang II-infused Adipo-KO mice compared to WT mice. Adenovirus-mediated adiponectin treatment improved the above phenotypes and the dysregulation of reactive oxygen species (ROS)-related mRNAs in Adipo-KO mice, whereas such amelioration was not observed in PPAR-alpha-KO mice despite adiponectin accumulation in heart tissue. In cultured cardiac fibroblasts, adiponectin improved the reduction of AMP-activated protein kinase (AMPK) activity and elevation of extracellular signal-regulated kinase 1/2 (ERK1/2) activity induced by Ang II. Adiponectin significantly enhanced PPAR-alpha activity, whereas the adiponectin-dependent PPAR-alpha activation was diminished by Compound C, an inhibitor of AMPK.
  
  
  CONCLUSIONS
  The present study suggests that adiponectin protects against Ang II-induced cardiac fibrosis possibly through AMPK-dependent PPAR-alpha activation.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2-B5, Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Fujita
authors.forename: Norikazu
authors.initials: N
authors.lastname: Maeda
authors.forename: Mina
authors.initials: M
authors.lastname: Sonoda
authors.forename: Koji
authors.initials: K
authors.lastname: Ohashi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hibuse
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nishizawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishida
authors.forename: Aki
authors.initials: A
authors.lastname: Hiuge
authors.forename: Akifumi
authors.initials: A
authors.lastname: Kurata
authors.forename: Shinji
authors.initials: S
authors.lastname: Kihara
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000256:Adenoviridae / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000804:Angiotensin II; D000818:Animals; D005355:Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000473:pathology
chemical_list: D052242:Adiponectin; D047493:PPAR alpha; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D011494:Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D000091162:AMP-Activated Protein Kinase Kinases