Mitochondrial SIRT2-mediated CPT2 deacetylation prevents diabetic cardiomyopathy by impeding cardiac fatty acid oxidation.

ABSTRACT: Dysregulated energy metabolism, particularly lipid metabolism disorders, has been identified as a key factor in the development of diabetic cardiomyopathy (DCM). Sirtuin 2 (SIRT2) is a deacetylase involved in the regulation of metabolism and cellular energy homeostasis, yet its role in the progression of DCM remains unclear. We observed significantly reduced SIRT2 expression in DCM model mice. Cardiac-specific overexpression of SIRT2 protected mice from streptozotocin/high-fat diet (STZ/HFD)-induced insulin resistance (IR), cell apoptosis, and cardiac dysfunction, whereas its downregulation exacerbated these conditions. Moreover, we found that SIRT2 regulated cardiac lipid accumulation and fatty acid oxidation (FAO), and identified its localization in cardiac mitochondria. Mechanistically,

SUBMITTER: Guo Y 

PROVIDER: S-EPMC11705638 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature