In this study, we found that SIRT5 could be negatively regulated by RIP140 (Figure 4) and overexpression of SIRT5 was capable of reversing RIP140-induced cardiac hypertrophy (Figure 5), suggesting that the functional antagonism of RIP140 and PGC-1α in cardiac energy metabolism is possibly associated with the regulation of SIRT5. This evidence concerns the gene SIRT5 and cardiac hypertrophy.