title: Omentin functions to attenuate cardiac hypertrophic response.
abstract: Cardiac hypertrophy occurs in many obesity-related conditions. Omentin is an adipose-derived plasma protein that is downregulated under obese conditions. Here, we investigated whether omentin modulates cardiac hypertrophic responses in vivo and in vitro. Systemic administration of an adenoviral vector expressing human omentin (Ad-OMT) to wild-type (WT) mice led to the attenuation of cardiac hypertrophy, fibrosis and ERK phosphorylation induced by transverse aortic constriction (TAC) or angiotensin II infusion. In cultured cardiomyocytes, stimulation with phenylephrine (PE) led to an increase in myocyte size, which was prevented by pretreatment with human omentin protein. Pretreatment of cardiomyocytes with omentin protein also reduced ERK phosphorylation in response to PE stimulation. Ad-OMT enhanced phosphorylation of AMP-activated protein kinase (AMPK) in the heart of WT mice after TAC operation. Blockade of AMPK activation by transduction with dominant-negative mutant forms of AMPK reversed the inhibitory effect of omentin on myocyte hypertrophy and ERK phosphorylation following PE stimulation. Moreover, fat-specific transgenic mice expressing human omentin showed reduced cardiac hypertrophy and ERK phosphorylation following TAC surgery compared to littermate controls. These data suggest that omentin functions to attenuate the pathological process of myocardial hypertrophy via the activation of AMPK in the heart, suggesting that omentin may represent a target molecule for the treatment of cardiac hypertrophy.
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: rshibata@med.nagoya-u.ac.jp.
authors.forename: Rei
authors.initials: R
authors.lastname: Shibata
authors.affiliation: Molecular Cardiovascular Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kambara
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Uemura
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Hiramatsu-Ito
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Enomoto
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yuasa
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Joki
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Hayakawa
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Department of Biomedical Informatics, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kihara
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.affiliation: Molecular Cardiovascular Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: nouchi@med.nagoya-u.ac.jp.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006332:Cardiomegaly / Q000188:drug therapy* / Q000473:pathology; D003251:Constriction, Pathologic; D016207:Cytokines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D058851:GPI-Linked Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D037102:Lectins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016207:Cytokines; D058851:GPI-Linked Proteins; C432397:ITLN1 protein, human; D037102:Lectins; D010656:Phenylephrine; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated protein kinase; Cardiac hypertrophy; Fibrosis; Omentin