LAUSR

Obesity has become a serious global public health problem, and cardiomyopathy caused by obesity has been paid more and more attention in recent years. As an important protein involved in glucose and lipid metabolism, G protein-coupled receptor 40 (GPR40) exerts cardioprotective effects in some disease models. The aim of this study was to explore whether GPR40 plays a protective role in obesity-induced cardiomyopathy. We established an obesity model by feeding rats with a high-fat diet, and H9c2 cells were stimulated with palmitic acid to mimic high-fat stimulation. Overexpression of GPR40 was achieved by infection with lentivirus or cDNA plasmids. Obesity-induced cardiac injury models exhibit cardiac dysfunction, myocardial hypertrophy and collagen accumulation, accompanied by increased inflammation, oxidative stress and apoptosis. However, GPR40 overexpression attenuated these alterations. Its anti-inflammatory effect may be through inhibiting the nuclear factor-κB pathway, and the anti-oxidative stress may be through activating the nuclear transcription factor erythroid 2-related factor 2 pathway. For the mechanism of GPR40 against obese cardiomyopathy, GPR40 overexpression not only activated the sirtuin 1 (SIRT1)- liver kinase B1 (LKB1)- AMP-activated protein kinase (AMPK) pathway, but also enhanced the binding of SIRT1 to LKB1. The anti-fibrotic, anti-inflammatory, anti-oxidative stress and anti-apoptotic effects of GPR40 overexpression were inhibited by SIRT1 small interfering RNA. In conclusion, GPR40 overexpression protects against obesity-induced cardiac injury in rats, possibly through the SIRT1- LKB1- AMPK pathway.