Nonalcoholic fatty liver disease (NAFLD) occurs in patients with type 2 diabetes mellitus (T2DM). Trelagliptin is an important member of the Gliptins family, which has been recently licensed for the treatment of T2DM. However, the pharmacological function of trelagliptin in NAFLD has not been previously reported. In this study, we aimed to investigate the roles of trelagliptin in the development of NAFLD in a mouse model. To induce NAFLD disease, C57BL/6 mice were fed a high‐fat diet for 10 weeks. Our results indicate that trelagliptin reduced plasma lipid levels in NAFLD mice by reducing triglycerides, total cholesterol, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol. Treatment with trelagliptin exhibited an improvement in insulin resistance. More important, trelagliptin improved liver function by reducing alanine transaminase, aspartate transaminase, lactate dehydrogenase, and total bile acid. In addition, trelagliptin ameliorated oxidative stress in the liver of NAFLD mice by reducing malondialdehyde and increasing the levels of reduced glutathione and superoxide dismutase activity. Also, the enzyme‐linked immunosorbent assay results indicate that trelagliptin‐treated mice displayed anti‐inflammatory properties by reducing the levels of interleukin 1β (IL‐1β), IL‐6, and tumor necrosis factor‐α. Hematoxylin and eosin and Oil red O staining show that trelagliptin treatment ameliorates liver tissue damage and hepatic lipid deposition. Mechanistically, we found that the administration of trelagliptin reduced the activity of hepatic nuclear factor‐κB but increased the activity of AMP‐activated protein kinase. These findings suggest that trelagliptin might become a promising therapeutic agent for the treatment of NAFLD.

中文翻译：

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海藻糖素对高脂饮食诱导的非酒精性脂肪肝小鼠的保护作用

非酒精性脂肪肝疾病（NAFLD）发生在2型糖尿病（T2DM）患者中。Trelagliptin是Gliptins家族的重要成员，该家族最近获得了T2DM的治疗许可。但是，曲拉格列汀在NAFLD中的药理作用尚未见报道。在这项研究中，我们旨在调查海藻糖蛋白在小鼠模型中NAFLD发育中的作用。为了诱导NAFLD疾病，给C57BL / 6小鼠喂食高脂饮食10周。我们的结果表明，曲拉格列汀可通过降低甘油三酸酯，总胆固醇，低密度脂蛋白胆固醇和高密度脂蛋白胆固醇来降低NAFLD小鼠的血脂水平。用曲格列汀治疗显示出胰岛素抵抗的改善。更重要，海藻糖素通过减少丙氨酸转氨酶，天冬氨酸转氨酶，乳酸脱氢酶和总胆汁酸来改善肝脏功能。另外，曲拉格列汀通过减少丙二醛和增加减少的谷胱甘肽和超氧化物歧化酶活性的水平，减轻了NAFLD小鼠肝脏的氧化应激。此外，酶联免疫吸附试验结果表明，经曲格列汀治疗的小鼠可通过降低白介素1β（IL-1β），IL-6和肿瘤坏死因子α的水平来显示抗炎特性。苏木精和曙红和油红O染色表明，曲拉格列汀治疗可改善肝组织损伤和肝脂质沉积。机械上，我们发现，曲拉格列汀的使用降低了肝核因子κB的活性，但增加了AMP激活的蛋白激酶的活性。这些发现表明，曲拉格列汀可能成为有希望的NAFLD治疗剂。