Diabetic cardiomyopathy is a primary cause of increased morbidity and mortality in diabetics. Evidence has suggested a pivotal role for interrupted mitochondrial dynamics and quality control machinery in the onset and development of diabetic cardiomyopathy. Sequestosome 1 (SQSTM1) is a major reporter of selective autophagic activity. Other than controlling the expression of genes involved in mitochondrial biogenesis, recently peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) was reported to directly affect SQSTM1 gene expression. Calcineurin, a pivotal mediator of cardiac hypertrophy, has been also linked to enhanced expression of SQSTM1. This study aimed to test the cardioprotective effects of adding ω-3 polyunsaturated fatty acids (PUFAs) to metformin in a rat model of type 2 diabetes mellitus and to evaluate the molecular mechanisms underlying their effects on mitochondrial quality. Diabetes was induced in male Sprague Dawley rats by a high-fat diet for 6 weeks, followed by a low-dose streptozotocin (35 mg/kg). Diabetic...

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