Carnitine Palmitoyltransferase 1A Alleviates Cardiac Injury and Mitochondrial Dysfunction in Diabetic Cardiomyopathy

Diabetic cardiomyopathy (DCM) involves myocardial structural and functional remodeling, in which mitochondrial dysfunction and oxidative stress play central roles.Carnitine palmitoyltransferase 1A (CPT1A) may participate in diabetic cardiac injury, but its underlying mechanism remains unclear.A type 2 diabetes mouse model was established using a high-fat diet and low-dose streptozotocin, while H9c2 cardiomyocytes were exposed to high glucose and palmitic acid.CPT1A was overexpressed using AAV9 in mice and a lentiviral vector in cells.Cardiac injury, lipid metabolism, oxidative stress, and mitochondrial function were assessed through biochemical, histological, RT-qPCR and Western blot analyses.The regulatory relationship between FOXA1 and CPT1A was examined using gainand loss-of-function approaches.CPT1A expression was reduced in diabetic myocardial tissues and high-glucose/palmitate-treated H9c2 cells.CPT1A overexpression attenuated cardiac injury, partially improved FBG, LDL, TC and TG levels, reduced cardiomyocyte hypertrophy and fibrosis-related gene expression, restored mitochondrial respiratory chain activity and ATP production, and alleviated oxidative stress.FOXA1 was identified as a potential upstream regulator of CPT1A.FOXA1 overexpression reduced cardiomyocyte injury, whereas FOXA1 knockdown aggravated mitochondrial dysfunction, which was partially reversed by CPT1A restoration.CPT1A alleviates diabetic cardiac injury by preserving mitochondrial function and limiting oxidative stress.The FOXA1-CPT1A axis may represent a potential therapeutic target for DCM.