Liraglutide significantly reduced lipid droplet formation and myocardial fibrosis in diabetic cardiomyopathy models by enhancing AMPK activation and improving insulin signaling.
Does liraglutide reduce lipid droplet accumulation and myocardial fibrosis in preclinical models of diabetic cardiomyopathy?
Liraglutide mitigates diabetic cardiomyopathy in preclinical models by reducing lipid accumulation and fibrosis through AMPK activation.
BACKGROUND: Diabetes is a primary contributor to diabetic cardiomyopathy (DbCM), which is marked by metabolic imbalances such as elevated blood glucose and lipid levels, leading to significant structural and functional alterations in the myocardium. Elevated free fatty acids (FFAs) and hyperglycemia play critical roles in DbCM development, with FFAs inducing insulin resistance in cardiomyocytes and promoting lipid accumulation, resulting in oxidative stress and fibrosis. Current research suggests that glucagon-like peptide-1 (GLP-1) receptor agonists may effectively mitigate DbCM, although an effective treatment for this condition remains elusive, and the precise mechanisms of this protective effect are not fully understood. METHODS: In this study, we aimed to replicate diabetic glucolipotoxic conditions by treating differentiated H9c2 cells with high glucose and free fatty acids. Additionally, a diabetic cardiomyopathy model was induced in mice through high-fat diets. Both in vitro and in vivo models were used to investigate the protective effects of liraglutide on cardiomyocytes and elucidate its underlying molecular mechanisms. RESULTS: Our findings indicate that liraglutide significantly reduces lipid droplet (LD) formation and myocardial fibrosis, as evidenced by decreased expression of fibrosis markers, including TGF-β1 and collagen types I and III. Liraglutide also enhanced AMP-activated protein kinase (AMPK) activation, which improved mitochondrial function, increased antioxidant gene expression, enhanced insulin signaling, and reduced oxidative stress. CONCLUSIONS: These results demonstrate the potential therapeutic role of liraglutide in managing diabetes-related cardiac complications, offering a comprehensive approach to improving cardiac outcomes in patients with diabetes.
Kuo et al. (Wed,) conducted a other in Diabetic cardiomyopathy (n=30). Liraglutide vs. High-fat diet (HFD) or High glucose + FFAs was evaluated on Lipid droplet accumulation and myocardial fibrosis markers (TGF-β1, collagen I and III). Liraglutide significantly reduced lipid droplet formation and myocardial fibrosis in diabetic cardiomyopathy models by enhancing AMPK activation and improving insulin signaling.