Epigenetically modulated MTCH2 and regulated ATP5 in the liver of obese mice subjected to strength training

Resumo (EN)

Obesity-induced hepatic lipid accumulation disrupts tissue metabolism and contributes to Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Physical exercise is a key strategy to counteract these effects by improving insulin sensitivity and modulating inflammatory and metabolic pathways. This study investigated the effects of resistance training in obese Swiss mice divided into Control (CTRL), Sedentary Obese (SOB), and Trained Obese (TOB) groups. Obesity was induced by a high-fat diet (HFD), and TOB animals underwent an 8-week resistance training protocol. Exercise restored hepatic insulin signaling by increasing AKT phosphorylation and reduced the expression of CDK4 and CDK6, proteins linked to cell proliferation, while decreasing Metalloproteinase 2 (MMP2) activity. Moreover, training enhanced mitochondrial biogenesis and oxidative capacity, increasing ATP5 protein expression. Importantly, resistance training epigenetically modulated the MTCH2 promoter region, reversing the obesity-induced upregulation of MTCH2 expression. These adaptations suggest that exercise mitigates hepatic metabolic dysfunction through molecular and epigenetic mechanisms. Collectively, our findings provide novel evidence that resistance exercise promotes mitochondrial and insulin signaling remodeling, reinforcing its therapeutic potential in obesity management.