Endurance exercise resistance to lipotoxic cardiomyopathy is associated with cardiac NAD/dSIR2/ pathway activation in old .

Lipotoxic cardiomyopathy is caused by excessive lipid accumulation in myocardial cells and it is a form of cardiac dysfunction. Cardiac overexpression prevents lipotoxic cardiomyopathy induced by a high-fat diet (HFD). The level of NAD and expression upregulate the transcriptional activity of PGC-1α. Exercise improves cardiac NAD level and PGC-1α activity. However, the relationship between exercise, NAD/dSIR2/ pathway and lipotoxic cardiomyopathy remains unknown. In this study, flies were fed a HFD and exercised. The heart gene was specifically expressed or knocked down by UAS/hand-Gal4 system. The results showed that either a HFD or knockdown remarkably increased cardiac TG level and expression, reduced heart fractional shortening and diastolic diameter, increased arrhythmia index, and decreased heart NAD level, dSIR2 protein, and expression levels. Contrarily, either exercise or overexpression remarkably reduced heart TG level, expression and arrhythmia index, and notably increased heart fractional shortening, diastolic diameter, NAD level, dSIR2 level, and heart and expression. Therefore, we declared that exercise training could improve lipotoxic cardiomyopathy induced by a HFD or cardiac knockdown in old The NAD/dSIR2/ pathway activation was an important molecular mechanism of exercise resistance against lipotoxic cardiomyopathy.