| 卢超,柯雅妮,胡洁.鸢尾素通过调控AKT/mTOR/SREBP-1信号通路改善非酒精性脂肪肝脂代谢[J].浙江中西医结合杂志,2024,34(12): |
| 鸢尾素通过调控AKT/mTOR/SREBP-1信号通路改善非酒精性脂肪肝脂代谢 |
| Irisin improves lipid metabolism in nonalcoholic fatty liver by regulating the AKT / mTOR / SREBP-1 signaling pathway |
| 投稿时间：2024-06-21 修订日期：2024-09-13 |
| DOI： |
| 中文关键词: 鸢尾素(Irisin) 非酒精性脂肪肝(NAFLD) AKT mTOR SREBP-1 PPAR |
| 英文关键词:Irisin non-alcoholic fatty liver disease (NAFLD) AKT mTOR SREBP-1 PPAR |
| 基金项目:浙江省医药卫生科技计划项目 |
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| 中文摘要: |
| 目的：探讨鸢尾素（Irisin）调节AKT/mTOR/SREBP-1信号通路对小鼠非酒精性脂肪肝（NAFLD）肝细胞脂代谢的影响。
方法：采用棕榈酸/油酸诱导小鼠肝细胞AML12构建NAFLD模型，再用200ng/ml的Irisin干预，CCK8法检测肝细胞增殖活性，油红O染色观察脂肪沉积情况，免疫印迹法检测磷酸化的蛋白激酶B（p-AKT）、哺乳动物雷帕霉素靶蛋白（p-mTOR）、核糖体蛋白S6激酶（p-P70S6K）及甾醇调节元件结合蛋白1（SREBP1）的表达，并分别使用AKT抑制剂和激动剂、mTOR抑制剂和激动剂干预，明确Irisin的作用位点。同时测定过氧化物酶体增殖激活受体（PPAR）及肝型脂肪酸结合蛋白（L-FABP）、下游靶基因脂肪酸合成酶（FAS）、乙酰辅酶A羧化酶1（ACC1）和硬脂酰辅酶A去饱和酶1（SCD1）的表达情况。
结果：NAFLD模型中，p-AKT、p-mTOR、p-P70S6K、SREBP1蛋白表达显著升高（P<0.05），Irisin能降低上述蛋白的表达(P<0.05)，Irisin的作用与AKT抑制剂及mTOR抑制剂有协同作用，并能被AKT激动剂及mTOR激活剂逆转（P<0.05）。并且Irisin能抑制FAS、ACC1及SCD1的表达，上调PPARα，下调PPARγ和L-FABP的表达（P<0.05），从而减轻肝细胞内脂肪沉积。
结论：Irisin通过抑制AKT/mTOR/SREBP-1信号通路改善NAFLD肝细胞脂代谢。 |
| 英文摘要: |
| Objective: To investigate the effect of Irisin on AKT/mTOR/SREBP-1 signaling pathway in cellular model of non-alcoholic fatty liver disease (NAFLD) and regulating lipid metabolism.
Methods: The cellular model of NAFLD was constructed using palmitate/oleic acid induced mouse hepatocytes AML 12, With an additional Irisin intervention of 200 ng/ml, The proliferative activity of hepatocytes was measured by CCK 8, and fat deposition was observed by oil red O staining, The expression of phosphorylated protein kinase B (p-AKT), animal target of rapamycin (p-mTOR), ribosomal protein S6 kinase (p-P70S6K) and sterol regulatory element binding protein 1 (SREBP1) were detected by immunoblotting, And the intervention with AKT inhibitors and agonists, mTOR inhibitors and agonists, respectively, To define the site of action of Irisin. The expression of peroxisome proliferation-activated receptor (PPAR), hepatic type fatty acid binding protein (L-FABP), downstream target genes fatty acid synthase (FAS), acetyl-CoA carboxylase 1 (ACC1) and stearyl-CoA desaturase 1 (SCD 1) were also determined.
Results: In the NAFLD model, the expression of p-AKT, p-mTOR, p-P70S6K and SREBP1 was significantly increased (P<0.05), Irisin reduced the expression of the above proteins (P<0.05), the effect of Irisin was synergistic with AKT inhibitors and mTOR inhibitors, and could be reversed by AKT agonists and mTOR activators (P<0.05). In addition, Irisin can inhibit the expression of FAS, ACC1 and SCD1, up-regulate PPARα, and downregulate the expression of PPARγand L-FABP (P <0.05), Thus alleviating the internal fat deposition in hepatocytes.
Conclusions: Irisin Improve hepatic cell lipid metabolism in NAFLD by inhibiting the AKT / mTOR / SREBP-1 signaling pathway. |
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