Abstract
BACKGROUND: Recent studies have shown that liraglutide, a glucagon-like peptide-1 receptor agonist, has unexpected cardioprotective effects. However, the distinctive effects of liraglutide on diabetic cardiomyopathy (DCM), particularly its effect on mitophagy, have not been fully elucidated. AIM: To investigate the effects of liraglutide on cardiac damage and mitophagy in DCM rats. METHODS: A high-fat diet and streptozotocin were used to induce DCM in rats. After 12 weeks of liraglutide treatment, rats underwent assessments of cardiac function, serum biochemical parameters, histological changes, apoptosis index, and protein levels. Furthermore, neonatal rat cardiomyocytes (NRCMs) were exposed to 25 mmol/L glucose plus 250 μmol/L palmitate (high glucose + palmitic acid), with or without 200 nmol/L liraglutide, to investigate the effects of liraglutide on cardiomyocyte injury and the underlying mechanisms. RESULTS: Liraglutide improved myocardial function and ameliorated cardiac damage in DCM rats, as indicated by reduced myocardial apoptosis, hypertrophy, and interstitial fibrosis (P < 0.05). In NRCMs, Liraglutide alleviated mitochondrial morphological and functional damage as well as oxidative stress, improved mitophagic defects, and reduced cell apoptosis (P < 0.05). Mechanistically, liraglutide alleviated NRCMs damage by enhancing mitophagy mediated by the adenosine monophosphate-activated protein kinase (AMPK)-Parkin signaling pathway, which was evidenced by the reversal of its effects upon compound C treatment. CONCLUSION: Liraglutide exerted cardioprotective effects in DCM rats by inhibiting cardiomyocyte apoptosis and promoting mitophagy mediated by the AMPK-Parkin signaling pathway.