SIRT6: A potential therapeutic target for diabetic cardiomyopathy

The abnormal lipid metabolism in diabetic cardiomyopathy can cause myocardial mitochondrial dysfunction, lipotoxicity, abnormal death of myocardial cells, and myocardial remodeling. Mitochondrial homeostasis and normal lipid metabolism can effectively slow down the development of diabetic cardiomyopathy. Recent studies have shown that SIRT6 may play an important role in the pathological changes of diabetic cardiomyopathy such as myocardial cell death, myocardial hypertrophy, and myocardial fibrosis by regulating mitochondrial oxidative stress and glucose and lipid metabolism. Therefore, understanding the function of SIRT6 and its role in the pathogenesis of diabetic cardiomyopathy is of great significance for exploring and developing new targets and drugs for the treatment of diabetic cardiomyopathy. This article reviews the latest findings of SIRT6 in the pathogenesis of diabetic cardiomyopathy, focusing on the regulation of mitochondria and lipid metabolism by SIRT6 to explore potential clinical treatments. SIRT6 can reduce abnormal accumulation of intracellular lipids and improve cellular glucose uptake and utilization by regulating the expression of fatty acid transporters and glucose transporters. In the nucleus, SIRT 6 can bind to a variety of substances to form a complex, thereby activating the transcription of antioxidant genes and repairing reactive oxygen‐mediated mtDNA damage. In addition, SIRT 6 inhibits telomere dysfunction by binding to telomeres, thereby reducing mitochondrial mtDNA damage.