Omarigliptin protects against nonalcoholic fatty liver disease by ameliorating oxidative stress and inflammation.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a prevalent liver disease with high morbidity. Omarigliptin is a novel antidiabetic drug that inhibits dipeptidyl peptidase-4 and alleviates inflammation and insulin resistance. In the present study, the anti-inflammatory and antioxidative stress property of omarigliptin will be investigated to explore the potential therapeutic effects of omarigliptin on NAFLD in mice models. A high-fat diet (HFD) was used to induce a NAFLD model in mice. Hematoxylin-eosin staining and detection on the concentrations of total cholesterol (TC) and triglyceride (TG) were used to evaluate lipid accumulation of the liver tissues. Liver function was evaluated by measuring aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase. The insulin resistance index, the concentration of glucose, and insulin in the serum were determined. The levels of malondialdehyde and superoxide dismutase activities were detected to access the oxidative stress state. The concentrations of interleukin (IL)-1α, IL-6, and CXCL1 were measured using an enzyme-linked immunosorbent assay. Western blot analysis was used to determine the expression levels of nuclear factor kappa B (NF-κB) p65 and SIRT1 in the liver tissues. Significant elevated body weight and liver weight, marked macrovesicular steatosis combined with hepatocellular ballooning on the liver tissues, accumulated TC and TG concentrations, damaged liver function, increased oxidative stress, and elevated production of inflammatory factors were all induced with an HFD and significantly reversed by treatment with omarigliptin. Also, the activated NF-κB signaling pathway, as well as suppressed SIRT1 expression level, were significantly reversed by omarigliptin. Omarigliptin protected against NAFLD by ameliorating oxidative stress and inflammation.