Liraglutide protects cardiac function in diabetic rats through the PPARα pathway

Increasing evidence shows that diabetes causes cardiac dysfunction. We hypothesized that a glucagon-like peptide-1 analogue, liraglutide, would attenuate cardiac dysfunction in diabetic rats. Twenty-four Sprague Dawley (SD) rats were divided into 2 groups fed either a normal diet (normal, n = 6) or a high-fat diet (HFD, n = 18) for 4 weeks. Then, the HFD rats were injected with streptozotocin (STZ) to create a diabetic rat model. Diabetic rats were divided into 3 subgroups receiving vehicle (diabetic, n = 6), a low dose of liraglutide (Llirag, 0.2 mg/kg/day, n = 6) or a high dose of liraglutide (Hlirag, 0.4 mg/kg/day, n = 6). Metabolic parameters, systolic blood pressure, heart rate, left ventricular (LV) function, and whole genome expression of the heart were determined. Diabetic rats developed insulin resistance, increased blood lipid levels and oxidative stress, and impaired LV function, serum adiponectin, NO. Liraglutide improved insulin resistance, serum adiponectin, NO, heart rate and LV function and reduced blood triglyceride, total cholesterol levels and oxidative stress. Moreover, liraglutide increased heart Nr1h3 , Ppar-α and Srebp expression and reduced Dgat , and Angptl3 expression. Liraglutide prevented in cardiac dysfunction by activating the PPARα pathway to inhibit Dgat expression and oxidative stress in diabetic rats.