Metformin attenuates cardiac remodeling in mice through the Nrf2/Keap1 signaling pathway

Obesity results in a variety of metabolic alterations that may contribute to abnormalities in cardiac structure and function. Although metformin (Met) has been previously reported to exhibit beneficial effects against cardiomyopathy associated obesity, the mechanism underlying this observation remains unclear. The aim of the present study was to investigate the status of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/kelch-like ECH-associated protein 1 (Keap1) system underlying the protective effects of Met against cardiac remodeling. High-fat diet-induced obesity mouse models were first generated, which were subsequently treated with Met. Metabolic parameters, heart weight index and degree of cardiac fibrosis were examined. The expression levels of genes and proteins associated with the Nrf2/Keap1 signaling pathway were assessed using reverse transcription-quantitative PCR and western blotting. In obese mice, Met treatment significantly ameliorated the obesity phenotype, improved metabolic disorders, reduced the heart weight index and attenuated cardiac fibrosis. The cardioprotective effects of Met may be mediated through the promotion of Keap1 degradation whilst increasing the expression of Nrf2 and associated downstream antioxidant factors.