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首页> 外文期刊>Journal of biochemical and molecular toxicology >The protective effects of trelagliptin on high-fat diet-induced nonalcoholic fatty liver disease in mice
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The protective effects of trelagliptin on high-fat diet-induced nonalcoholic fatty liver disease in mice

机译：特拉格利特汀对小鼠高脂饮食诱导的非酒精性脂肪肝病的保护作用

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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 im-munosorbent 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.
机译：非酒精性脂肪肝（NAFLD）发生在2型糖尿病（T2DM）患者中。曲拉格列汀是格列汀家族的一个重要成员，该家族最近被授权用于治疗T2DM。然而，曲拉格列汀在NAFLD中的药理作用尚未报道。在这项研究中，我们旨在通过小鼠模型研究曲拉格列汀在NAFLD发展中的作用。为了诱发NAFLD疾病，C57BL/6小鼠被喂食高脂饮食10周。我们的结果表明，曲拉格列汀通过降低甘油三酯、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。用曲拉格列汀治疗可改善胰岛素抵抗。更重要的是，曲拉格列汀通过降低丙氨酸转氨酶、天冬氨酸转氨酶、乳酸脱氢酶和总胆汁酸来改善肝功能。此外，trelagliptin通过降低丙二醛、提高还原型谷胱甘肽水平和超氧化物歧化酶活性，改善NAFLD小鼠肝脏的氧化应激。此外，酶联免疫吸附试验结果表明，通过降低白细胞介素1β（IL-1β）、白细胞介素6和肿瘤坏死因子-α的水平，曲拉格列汀治疗的小鼠显示出抗炎特性。苏木精、曙红和油红O染色显示，曲拉脂蛋白治疗可改善肝组织损伤和肝脂质沉积。在机制上，我们发现给予曲拉格列汀降低了肝细胞核因子-κB的活性，但增加了AMP活化蛋白激酶的活性。这些发现表明，曲拉格列汀可能成为治疗NAFLD的一种有前途的治疗剂。

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