Medical Administration, Suez Canal University, Ismailia, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
Life Sci. 2020 Jul 15;253:117725. doi: 10.1016/j.lfs.2020.117725. Epub 2020 Apr 27.
Non-alcoholic fatty liver disease (NAFLD) is a common liver disease. This study aimed to evaluate the role of exenatide compared with metformin in halting the progression of fatty liver stimulated by a high-fat diet (HiFD) in rats.
Thirty male Wistar rats were allocated into 6 groups, 5 rats per each group. Group I: maintained on normal diet (normal group) for fourteen weeks. The other five groups were kept on HiFD throughout the experiment, HiFD was administered beside pharmacological treatments/or vehicle. Group II: (NAFLD control group), group III: received metformin (60 mg/kg/day, P.O.), group IV-VI: received exenatide (10, 20, and 40 μg/kg/day, S.C.) respectively for 7 weeks. At the end of the therapeutic period, fasting blood glucose was determined, and body weight was registered. Rats were sacrificed, and blood samples were taken to measure serum insulin, lipids, and liver enzymes. The liver index and homeostasis model of insulin resistance (HOMA-IR) index were calculated. Further, livers were dissected for histopathological examination and Western blot analysis.
NAFLD control group showed hyperglycemia, hyperinsulinemia, increased liver enzymes, hypertriglyceridemia, elevated hepatic lipid peroxides, and inflammatory mediators (interlukin 6, nuclear factor-κB, tumor necrosis factor-α and Toll-like receptor4) in addition to hepatic fatty degeneration. In a dose-dependent manner, exenatide significantly improved most of the above mentioned markers in comparsion with NAFLD at P≤0.05.
The current results suggest that exenatide is equivalent to metformin in controlling insulin resistance, body weight gain, improving liver function, suppressing inflammation, and attenuating NAFLD progression in male rats.
非酒精性脂肪性肝病（NAFLD）是一种常见的肝脏疾病。本研究旨在评估艾塞那肽与二甲双胍在阻止高脂肪饮食（HiFD）刺激大鼠脂肪肝进展中的作用。
将 30 只雄性 Wistar 大鼠分为 6 组，每组 5 只。第 I 组：正常饮食（正常组）喂养 14 周。其余 5 组在整个实验过程中给予 HiFD，同时给予药物治疗/载体。第 II 组：（NAFLD 对照组），第 III 组：给予二甲双胍（60mg/kg/天，PO），第 IV-VI 组：分别给予艾塞那肽（10、20 和 40μg/kg/天，SC）治疗 7 周。在治疗期末，测定空腹血糖，记录体重。处死大鼠，取血样检测血清胰岛素、血脂和肝功能。计算肝指数和胰岛素抵抗稳态模型（HOMA-IR）指数。进一步，对肝脏进行解剖以进行组织病理学检查和 Western blot 分析。
NAFLD 对照组表现为高血糖、高胰岛素血症、肝酶升高、高三酰甘油血症、肝脂质过氧化和炎症介质（白细胞介素 6、核因子-κB、肿瘤坏死因子-α 和 Toll 样受体 4）升高，此外还有肝脂肪变性。艾塞那肽以剂量依赖性方式显著改善了与 NAFLD 相比上述大多数标志物，P≤0.05。
目前的结果表明，艾塞那肽在控制胰岛素抵抗、体重增加、改善肝功能、抑制炎症和减轻雄性大鼠非酒精性脂肪性肝病进展方面与二甲双胍相当。
