Ghrelin protects against obesity-induced myocardial injury by regulating the lncRNA H19/miR-29a/IGF-1 signalling axis.

Abstract

BACKGROUND:

Obesity is associated with the impairment of cardiac fitness and consequent ventricular dysfunction and heart failure. Ghrelin has been largely documented to be cardioprotective against ischaemia/reperfusion injury. However, the role of ghrelin in obesity-induced myocardial injury is largely unknown. This study sought to determine the cardiac effect of ghrelin against obesity-induced injury and the underlying mechanisms.

METHODS:

The effect of ghrelin was evaluated in a mouse model of obesity and a palmitic acid (PA)-treated cardiomyocyte cell line with or without ghrelin transfection. Gene and protein expression levels were determined by real-time PCR and western blot, respectively. Cell apoptosis was measured by flow cytometry analysis.

RESULTS:

In the present study, we found that both a high-fat diet (HFD) and PA treatment caused myocardial injury by increasing apoptosis and the expression of inflammatory cytokines. Overexpression of ghrelin reversed the effects induced by HFD or PA treatment. Knockdown of lncRNA H19 or overexpression of miR-29a abrogated the cardioprotective effects of ghrelin against apoptosis and inflammation. We also found that IGF-1 was a target gene of miR-29a and that H19 regulated IGF-1 expression via miR-29a. Overexpression of IGF-1 partially reversed the apoptosis and inflammation promoting effects of miR-29a.

CONCLUSIONS:

Our findings suggested that ghrelin protected against obesity-induced myocardial injury by regulating the H19/miR-29a/IGF-1 signalling axis, providing further evidence for the clinical application of ghrelin.

• Authors: Yang Liu, Xin-Yue Xu, Yang Shen, Chun-Feng Ye, Na Hu, Qing Yao, Xiu-Zi Lv, Sheng-Lan Long, Chao Ren, Yuan-Yuan Lang, Yan-Ling Liu
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 114 Pg. 104405 (06 2020) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 32084395 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Ghrelin
• H19 long non-coding RNA
• MIRN29 microRNA, mouse
• MicroRNAs
• RNA, Long Noncoding
• insulin-like growth factor-1, mouse
• Insulin-Like Growth Factor I

Topics

• Animals
• Apoptosis (genetics)
• Cell Line
• Disease Models, Animal
• Gene Expression Regulation (genetics)
• Ghrelin (genetics)
• Heart Injuries (etiology, genetics, pathology)
• Humans
• Insulin-Like Growth Factor I (genetics)
• Mice
• MicroRNAs (genetics)
• Myocytes, Cardiac (metabolism, pathology)
• Obesity (complications, genetics, pathology)
• RNA, Long Noncoding (genetics)
• Signal Transduction (genetics)
• Transfection