Activation of SIRT1 by resveratrol ameliorated cardiac injuries and improved mitochondrial biogenesis and function in diabetic cardiomyopathy mice.
Does resveratrol alleviate cardiac dysfunction and mitochondrial impairment in diabetic cardiomyopathy models?
Resveratrol ameliorates cardiac injuries in diabetic cardiomyopathy through PGC-1α-mediated mitochondrial regulation via SIRT1 activation.
Background . Diabetic cardiomyopathy (DCM) is a major threat for diabetic patients. Silent information regulator 1 (SIRT1) has a regulatory effect on mitochondrial dynamics, which is associated with DCM pathological changes. Our study aims to investigate whether resveratrol, a SRIT1 activator, could exert a protective effect against DCM. Methods and Results . Cardiac‐specific SIRT1 knockout (SIRT1 KO ) mice were generated using Cre‐loxP system. SIRT1 KO mice displayed symptoms of DCM, including cardiac hypertrophy and dysfunction, insulin resistance, and abnormal glucose metabolism. DCM and SIRT1 KO hearts showed impaired mitochondrial biogenesis and function, while SIRT1 activation by resveratrol reversed this in DCM mice. High glucose caused increased apoptosis, impaired mitochondrial biogenesis, and function in cardiomyocytes, which was alleviated by resveratrol. SIRT1 deletion by both SIRT1 KO and shRNA abolished the beneficial effects of resveratrol. Furthermore, the function of SIRT1 is mediated via the deacetylation effect on peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1α), thus inducing increased expression of nuclear respiratory factor 1 (NRF‐1), NRF‐2, estrogen‐related receptor‐α (ERR‐α), and mitochondrial transcription factor A (TFAM). Conclusions . Cardiac deletion of SIRT1 caused phenotypes resembling DCM. Activation of SIRT1 by resveratrol ameliorated cardiac injuries in DCM through PGC‐1α‐mediated mitochondrial regulation. Collectively, SIRT1 may serve as a potential therapeutic target for DCM.
Ma et al. (2017) studied Diabetic cardiomyopathy. Resveratrol vs. Control / SIRT1 KO was evaluated on Cardiac dysfunction and mitochondrial biogenesis/function. Activation of SIRT1 by resveratrol ameliorated cardiac injuries and improved mitochondrial biogenesis and function in diabetic cardiomyopathy mice.