| 夏雪梅,陈艳.TAK1通过PPARγ调控肝细胞胰岛素抵抗和脂质代谢的机制研究[J].浙江中西医结合杂志,2025,35(9): |
| TAK1通过PPARγ调控肝细胞胰岛素抵抗和脂质代谢的机制研究 |
| The Mechanism of TAK1 Regulating Insulin Resistance and Lipid Metabolism in Hepatocyte through PPAR γ |
| 投稿时间：2024-09-05 修订日期：2025-04-15 |
| DOI： |
| 中文关键词: 胰岛素抵抗 脂质代谢 TAK1 PPARγ |
| 英文关键词:Insulin resistance Lipid metabolism TAK1 PPARγ |
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| 中文摘要: |
| 目的 探究转化生长因子-β活化激酶1（TAK1）通过调控过氧化物酶体增殖物激活受体γ（PPARγ）对肝细胞胰岛素抵抗和脂质代谢的影响，并分析其机制。 方法 使用肿瘤坏死因子α（TNF-α）处理人肝细胞LO2构建胰岛素抵抗细胞模型，检测葡萄糖含量和摄取量，Western blot检测胰岛素抵抗相关蛋白胰岛素受体底物1（IRS1）、p-IRS1、蛋白激酶B（AKT）和p-AKT、脂质代谢相关蛋白脂联素（ADIPOQ）、肉毒碱棕榈酰基转移酶1A（CPT-1A）、脂肪酸合成酶（FAS）和低密度脂蛋白受体（LDLR）以及TAK1和PPARγ的表达水平。通过si-RNA对细胞中TAK1和PPARγ进行敲低处理，实时定量反转录聚合酶链式反应（qRT-PCR）检测转染效率，油红O染色检测细胞中的脂滴累积情况，同时检测胰岛素抵抗和脂质代谢水平。 结果 相较于对照组，TNF-α处理后细胞中的葡萄糖含量升高，摄取量减少，TAK1蛋白表达水平显著升高，而PPARγ、p-IRS1和p-AKT的蛋白表达水平显著降低，脂质代谢相关蛋白ADIPOQ、CPT-1A、和LDLR表达水平显著降低，FAS表达水平显著升高。敲低TAK1后，细胞中PPARγ表达水平显著升高，同时葡萄糖含量降低，摄取量升高，胰岛素抵抗相关蛋白p-IRS1和p-AKT表达水平也显著升高，细胞中脂滴累积减少，脂质代谢相关蛋白ADIPOQ、CPT-1A、和LDLR表达水平显著升高，FAS表达水平显著降低。而进一步敲低PPARγ后，以上趋势发生逆转。 结论 TAK1抑制可促进PPARγ表达，改善TNF-α诱导的LO2细胞胰岛素抵抗和脂质代谢紊乱，发挥肝脏保护作用。 |
| 英文摘要: |
| Abstract Objective To explore the effect of transforming growth factor-β activated kinase 1 (TAK1) on insulin resistance and lipid metabolism in hepatocyte by regulating peroxisome proliferator-activated receptor (PPARγ), and analyze its mechanism. Methods Using tumor necrosis actor-α (TNF-α) to treat human liver cell LO2 to construct an insulin resistance cell model, glucose content and uptake were detected. Western blot was used to detect the expression levels of insulin resistance related proteins insulin receptor substrate 1 (IRS1), p-IRS1, protein kinase B (AKT), and p-AKT, lipid metabolism related proteins adiponectin (ADIPOQ), carnitine palmitoyltransferase 1A (CPT-1A), fatty acid synthase (FAS), and low-density lipoprotein receptor (LDLR), as well as TAK1 and PPARγ. Knockdown treatment of TAK1 and PPARγ in cells was performed using si RNA, transfection efficiency was detected by quantitative reverse transcription polymerase chain reaction (qRT PCR), lipid droplet accumulation in cells was detected by Oil Red O staining, and insulin resistance and lipid metabolism levels were also measured. Results Compared with the control group, TNF-α treatment resulted in an increase in glucose content, a decrease in uptake, a significant increase in TAK1 protein expression, and a significant decrease in protein expression levels of PPARγ, p-IRS1, and p-AKT. The expression levels of lipid metabolism related proteins ADIPOQ, CPT-1A, and LDLR were significantly reduced, while the expression levels of FAS were significantly increased. After knocking down TAK1, the expression level of PPARγ in cells significantly increased, while glucose content decreased and uptake increased. The expression levels of insulin resistance related proteins p-IRS1 and p-AKT also significantly increased. The accumulation of lipid droplets in cells decreased. The expression levels of lipid metabolism related proteins ADIPOQ, CPT-1A, and LDLR were significantly increased, while the expression levels of FAS were significantly reduced. After further knocking down PPARγ, the above trend reversed. Conclusion Inhibition of TAK1 can promote the expression of PPARγ, improve the insulin resistance and lipid metabolism disorder of LO2 cells induced by TNF-α, and exert liver protective effects. |
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