Liraglutide ameliorates nonalcoholic fatty liver disease in diabetic mice via the IRS2/PI3K/Akt signaling pathway.

High prevalence of nonalcoholic fatty liver disease (NAFLD) among patients with type 2 diabetes has implicated the role of hepatic insulin resistance (IR) in the diseases. To better understand the underlying mechanism, we have evaluated the pathophysiological effects of Liraglutide on NAFLD via the insulin signaling pathway. A 2×2 factorial experiment was designed. High-fat diet (HFD)-induced NAFLD mice with diabetes were treated with Liraglutide for 10 weeks, while the control mice were saline-treated. Hepatic expressions of InsR, IGF-1R, IRS2, PI3K and Akt at mRNA and protein levels were analyzed with RT-PCR and Western blotting. Hematoxylin and eosin staining, Oil Red O staining and electron microscopy were used to visualize triglyceride accumulation in liver. Liraglutide significantly decreased body weight, fasting blood glucose levels and HOMA-IR scores in HFD mice. Compared with the control mice fed with chow diet, hepatic expressions of InsR, IRS2, PI3K and Akt at both mRNA and protein levels in HFD mice were significantly reduced, but upregulated after Liraglutide treatment. Furthermore, Liraglutide treatment was found to improve hepatic steatosis. The current study thereby provides evidence that Liraglutide ameliorates NAFLD and improves hepatic steatosis mainly by upregulation of the IRS2/PI3K/Akt signaling mediators.