Abstract
OBJECT: Obesity is an increase in body weight beyond the limitation of skeletal and physical requirement, as the result of an excessive accumulation of fat in the body. Obesity could increase the risk of myocardial fibrosis. (-)-Epigallocatechin-3-gallate (EGCG) is the most abundant substance in green tea and has been reported to have multiple pharmacological activities. However, there is not enough evidence to show that EGCG has a therapeutic effect on obesity-induced myocardial fibrosis. This study aims to investigate whether EGCG is a potential drug for obesity-induced myocardial fibrosis. METHODS: Obesity-induced myocardial fibrosis rat model was established by HFD feeding for 36 weeks. EGCG was intragastrically administered at 160 mg/kg/d for the last 4 weeks. The pathological changes of myocardial fibrosis were evaluated by tissue pathological staining and collagen quantification. Furthermore, total RNA was extracted from the heart for RNA-seq to identify the changes in the transcript profile, and the relevant hub genes were verified by quantitative real-time PCR and western blot. RESULTS: EGCG significantly relieved HFD diet-induced obesity and alleviated the pathology of myocardial fibrosis. Biochemical analysis showed that EGCG could relieve the burden of lipid metabolism and injury to the myocardium and transcript profile analysis showed that EGCG could alleviate obesity-induced myocardial fibrosis by increasing the level of Scn5a in the heart. Furthermore, quantitative real-time PCR and western blot analysis for SCN5A also confirmed this finding. CONCLUSION: Taken together, these results suggest that EGCG could protect against the obesity-induced myocardial fibrosis. EGCG plays an anti-myocardial fibrosis role by regulating the expression of SCN5A in the heart.