Figure 8.

Working model for the amelioration of cardiac dysfunction by exercise training in high-fat diet-fed obese mice. High-fat diet increases obesity and develops the type 2 diabetes (T2DM) phenotype that promotes cardiac metabolic remodeling, resulting in activation of inflammasome-mediated pyroptosis, a cell death mechanism. This leads to adverse cardiac remodeling signaling, including structural changes such as fibrosis formation and hypertrophy of cardiomyocytes that follow to fill the growing vacant extracellular space, and functional impairment due to reduced calcium handling through SERCA-2A that leads to cardiac dysfunction. Exercise training prevents HFD-induced development of the T2DM phenotype and upregulation of cardiac pyroptosis, as well as adverse cardiac remodeling, possibly by increasing cardioprotective H₂S signaling.