AUTHOR=Liu Yuansheng , Zhang Qian , Yang Lei , Tian Wencong , Yang Yinan , Xie Yuhang , Li Jing , Yang Liang , Gao Yang , Xu Yang , Liu Jie , Wang Yachen , Yan Jie , Li Guoxun , Shen Yanna , Qi Zhi 

TITLE=Metformin Attenuates Cardiac Hypertrophy Via the HIF-1α/PPAR-γ Signaling Pathway in High-Fat Diet Rats

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.919202

DOI=10.3389/fphar.2022.919202

ISSN=1663-9812

ABSTRACT=Coronary artery disease (CAD) and cardiac hypertrophy (CH) are two main causes of ischemic heart disease. Acute CAD may lead to left ventricular hypertrophy. Long-term and sustained CH is harmful and can gradually develop into cardiac insufficiency and heart failure. It is known that metformin (Met) can alleviate CH, however, the molecular mechanism is not fully understood. Herein, we used high-fat diet (HFD) rats and H9c2 cells to induce CH and clarify the potential mechanism of Met on CH. We found that Met treatment significantly decreased cardiomyocyte size, reduced LDH release and down-regulated the expressions of hypertrophy markers ANP, VEGF-A as well as GLUT1 either in vivo or in vitro. Meanwhile, the protein levels of HIF-1α and PPAR-γ were both decreased after Met treatment, and administrations of their agonists, deferoxamine (DFO) or rosiglitazone (Ros) markedly abolished the protective effect of Met on CH. Additionally, DFO treatment up-regulated the expression of PPAR-γ, whereas, Ros treatment did not affect the expression of HIF-1α. In conclusion, Met attenuates CH via HIF-1α/PPAR-γ signaling pathway.