Eskisehir Osmangazi University, Medicine School, Histology and Embryology Department, Eskisehir, Turkey.
Eskisehir Osmangazi University, Medicine School, Histology and Embryology Department, Eskisehir, Turkey.
Tissue Cell. 2019 Aug;59:62-69. doi: 10.1016/j.tice.2019.07.001. Epub 2019 Jul 2.
Nonalcoholic fatty liver disease (NAFLD) is a frequent health problem. The insulin resistance and endoplasmic reticulum (ER) stress have been suggested to play important roles in the development and progression of NAFLD. However these processes and correlations have not fully been understood yet. Azoramide, an antidiabetic drug, has the potential for reducing insulin resistance and ER stress in obese mice. To date, there is no study on the effects of azoramide in NAFLD. The aim of this study was to investigate the potential role of azoramide on insulin resistance and ER stress in NAFLD induced mice. Forty Swiss Albino mice were assigned into control, azoramide, fructose and fructose + azoramide groups. Azoramide group received a single dose of azoramide at 150 mg/kg/day by gavage between 71-77th days. Fructose group was treated with 30% fructose solution for 70 days to generate NAFLD. Fructose + azoramide group was treated with 30% fructose for 70 days and then with a single dose of 150 mg/kg/day azoramide for 7 days. At the end of experiment, blood of mice was taken via cardiac puncture, and the livers were excised and weighted. GRP78 and XBP-1 levels were examined with immunohistochemistry in liver tissues. Liver steatosis was evaluated with H&E, Oil-Red O and Sudan-Black staining. ALT, AST, triglyceride, total cholesterol, VLDL, LDL, HDL, fasting glucose and insulin levels were measured in serum. The body and liver weights, insulin resistance, ER-stress markers, lipid profile, AST, ALT and histopathological changes increased by fructose treatment. Azoramide treatment was generally reversed all these changes. These data offer the first evidence to show that azoramide may serve as a potential treatment agent in NAFLD through decreasing the ER-stress and insulin resistance.
非酒精性脂肪性肝病（NAFLD）是一种常见的健康问题。胰岛素抵抗和内质网（ER）应激被认为在 NAFLD 的发生和发展中起重要作用。然而，这些过程和相关性尚未完全被理解。阿佐酰胺是一种抗糖尿病药物，具有降低肥胖小鼠胰岛素抵抗和 ER 应激的潜力。迄今为止，尚无关于阿佐酰胺在 NAFLD 中作用的研究。本研究旨在探讨阿佐酰胺对诱导 NAFLD 的小鼠胰岛素抵抗和 ER 应激的潜在作用。将 40 只瑞士白化病小鼠分为对照组、阿佐酰胺组、果糖组和果糖+阿佐酰胺组。阿佐酰胺组在第 71-77 天每天通过灌胃给予 150mg/kg 阿佐酰胺单次剂量。果糖组用 30%果糖溶液处理 70 天以产生 NAFLD。果糖+阿佐酰胺组用 30%果糖处理 70 天，然后用 150mg/kg 阿佐酰胺单次剂量处理 7 天。实验结束时，通过心脏穿刺采集小鼠血液，并切除肝脏称重。用免疫组织化学法检测肝组织中 GRP78 和 XBP-1 水平。用 H&E、油红 O 和苏丹黑染色评估肝脂肪变性。在血清中测量 ALT、AST、甘油三酯、总胆固醇、VLDL、LDL、HDL、空腹血糖和胰岛素水平。果糖处理后，体重、肝重、胰岛素抵抗、ER 应激标志物、血脂谱、AST、ALT 和组织病理学变化增加。阿佐酰胺处理通常逆转了所有这些变化。这些数据首次提供证据表明，阿佐酰胺可能通过降低 ER 应激和胰岛素抵抗，成为 NAFLD 的潜在治疗药物。
