Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Emergency, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China.
J Biochem Mol Toxicol. 2021 Dec;35(12):e22914. doi: 10.1002/jbt.22914. Epub 2021 Sep 17.
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.
非酒精性脂肪性肝病（NAFLD）是一种发病率较高的常见肝脏疾病。奥马利格列汀是一种新型的抗糖尿病药物，可抑制二肽基肽酶-4，减轻炎症和胰岛素抵抗。在本研究中，将研究奥马利格列汀的抗炎和抗氧化应激特性，以探索奥马利格列汀在小鼠模型中对 NAFLD 的潜在治疗作用。采用高脂肪饮食（HFD）诱导小鼠 NAFLD 模型。使用苏木精-伊红染色和总胆固醇（TC）和甘油三酯（TG）浓度检测来评估肝脏组织中的脂质堆积。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。测定血清中胰岛素抵抗指数、葡萄糖和胰岛素浓度。检测丙二醛和超氧化物歧化酶活性水平以评估氧化应激状态。使用酶联免疫吸附试验测定白细胞介素（IL）-1α、IL-6 和 CXCL1 的浓度。采用 Western blot 分析来确定肝脏组织中核因子 kappa B（NF-κB）p65 和 SIRT1 的表达水平。HFD 可显著增加体重和肝脏重量，肝脏组织出现明显的大泡性脂肪变性伴肝细胞气球样变，TC 和 TG 浓度升高，肝功能受损，氧化应激增加，炎症因子产生增加，而奥马利格列汀治疗可显著逆转这些变化。此外，奥马利格列汀还可显著逆转激活的 NF-κB 信号通路以及抑制 SIRT1 表达水平。奥马利格列汀通过改善氧化应激和炎症来预防 NAFLD。
