Fig. 3

PPARα, pemafibrate, metformin and cellular abnormalities in diabetic cardiomyopathy (DCM). In diabetes, enhanced hepatic lipids, glucose and BCAA output are enhanced, resulting in lipids accumulation, increased O-GlcNAcylation and mTORC1 activation in heart. Along with the altered mitochondrial energy metabolism, these intracellular abnormalities contribute to the formation of cardiac hypertrophy and cardiac dysfunction. Pemafibrate, a novel selective PPARα modulator, is highly effective in activating PPARα than the conventional fibrates and having a better triglyceride-lowering activity through up-regulating not only hepatic fibroblast growth factor 21 (FGF21), but also lipoprotein lipase (LPL) in mice. Metformin is used in treating DCM due to its effect on reduces hepatic gluconeogenesis by inhibiting phosphoenolpyruvate carboxykinase (PEPCK). In addition, an effect of metformin in reducing circulating branched chain amino acids (BCAA) is observed in insulin-resistant mice. Further studies need to clarify if metformin may reduce cardiac hypertrophy through down-regulating BCAA-mediated mTORC1 pathway