Abstract: 【Objective】 To investigate the effect of sirtuin3 (SIRT3) on cardiomyocyte hypertrophy and myocardial energy metabolism under the regulation of peroxisome proliferator -activated receptor gamma coactivator -1α (PGC -1α). 【Methods】 Angiotensin II (Ang II) was used to establish the model of cardiomyocyte hypertrophy in primary culture of neonatal rat cardiomyocytes. PGC -1α was overexpressed by plasmid transfection and SIRT3 was knocked down by RNA interference. The expressions of PGC -1α

SIRT3

and the hypertrophic marker myosin heavy chain β(β -MHC)

were tested by Western blotting. Mitochondrial membrane potential level

ATP content

production of reactive oxygen species

and the mRNA levels of genes related to mitochondrial metabolism were investigated. 【Results】 PGC -1α overexpression significantly increased the protein expression level and enzyme activity of SIRT3 (P < 0.05). PGC -1α overexpression prevented Ang II -induced cardiomyocyte hypertrophy (P < 0.05)

increased ATP content (P < 0.05)

promoted the mRNA levels of mitochondrial synthesis genes (P < 0.05)

suppressed intracellular reactive oxygen species (P < 0.05)

and enhanced expressions of genes related to fatty acids metabolism and mitochondria oxidative phosphorylation (P < 0.05). Interestingly

all these cardiac protective effects of PGC -1α were reversed by SIRT3 interference (P < 0.05). 【Conclusions】Upregulation of SIRT3 contributes to the protective effect of PGC -1α against cardiomyocyte hypertrophy

mitochondrial dysfunction

and dysregulation of energy metabolism.