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.

中文翻译：

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奥马列汀通过改善氧化应激和炎症来预防非酒精性脂肪肝

非酒精性脂肪性肝病 (NAFLD) 是一种高发病率的常见肝病。Omarigliptin 是一种新型抗糖尿病药物，可抑制二肽基肽酶 4 并减轻炎症和胰岛素抵抗。在本研究中，将研究奥格列汀的抗炎和抗氧化应激特性，以探索奥格列汀对小鼠模型 NAFLD 的潜在治疗作用。使用高脂肪饮食 (HFD) 在小鼠中诱导 NAFLD 模型。苏木精-伊红染色和总胆固醇（TC）和甘油三酯（TG）浓度的检测用于评估肝组织的脂质积累。通过测量天冬氨酸氨基转移酶、丙氨酸氨基转移酶、碱性磷酸酶和乳酸脱氢酶来评估肝功能。胰岛素抵抗指数，测定血清中葡萄糖和胰岛素的浓度。检测丙二醛和超氧化物歧化酶活性水平以进入氧化应激状态。使用酶联免疫吸附测定法测量白细胞介素 (IL)-1α、IL-6 和 CXCL1 的浓度。Western印迹分析用于确定肝组织中核因子κB（NF-κB）p65和SIRT1的表达水平。体重和肝脏重量显着升高、大泡性脂肪变性合并肝组织上的肝细胞气球样变、TC 和 TG 浓度累积、肝功能受损、氧化应激增加和炎症因子产生升高均由 HFD 诱导，并通过 HFD 显着逆转。用奥格列汀治疗。此外，激活的 NF-κB 信号通路，以及抑制的 SIRT1 表达水平，被奥格列汀显着逆转。Omarigliptin 通过改善氧化应激和炎症来预防 NAFLD。