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: Kazuhiro Matsuo, Rei Shibata, Koji Ohashi, Takahiro Kambara, Yusuke Uemura, Mizuho Hiramatsu-Ito, Takashi Enomoto, Daisuke Yuasa, Yusuke Joki, Masanori Ito, Satoko Hayakawa, Hayato Ogawa, Shinji Kihara, Toyoaki Murohara, Noriyuki Ouchi
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 79 Pg. 195-202 (Feb 2015) ISSN: 1095-8584 [Electronic] England
• PMID: 25479337 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Cytokines
• GPI-Linked Proteins
• ITLN1 protein, human
• Lectins
• Phenylephrine
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Adiposity (drug effects)
• Animals
• Aorta (drug effects, metabolism, pathology)
• Cardiomegaly (drug therapy, pathology)
• Constriction, Pathologic
• Cytokines (administration & dosage, pharmacology, therapeutic use)
• GPI-Linked Proteins (administration & dosage, pharmacology, therapeutic use)
• Humans
• Lectins (administration & dosage, pharmacology, therapeutic use)
• Male
• Mice, Inbred C57BL
• Mice, Transgenic
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Phenylephrine (pharmacology)
• Rats
• Signal Transduction (drug effects)