GSK3 inhibitor ameliorates steatosis through the modulation of mitochondrial dysfunction in hepatocytes of obese patients.
GSK3 inhibitor ameliorates steatosis through the modulation of mitochondrial dysfunction in hepatocytes of obese patients.
复制标题
GSK3 抑制剂通过调节肥胖患者肝细胞中的线粒体功能障碍来改善脂肪变性。
DOI：
10.1016/j.isci.2021.102149
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发表时间：
2021-03-19
期刊：
影响因子：
5.8
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Li Y;Lin Y;Han X;Li W;Yan W;Ma Y;Lu X;Huang X;Bai R;Zhang H
肥胖是肝脂肪变性的重要危险因素，也是潜在的治疗靶点。肝线粒体弹性失调在肝脂肪变性中起关键作用。在此，我们发现从肥胖患者的人脂肪干细胞来源的肝细胞样细胞表现出肝脂肪变性的特征，并伴有线粒体复合物I亚单位的低表达和较低的氧化磷酸化水平。GSK 3抑制剂CHIR-99021通过上调参与线粒体生物合成的转录因子PGC-1α、TFAM和NRF 1的表达，促进肥胖患者肝细胞线粒体复合物I亚基NDUFB 8、NDUFB 9的表达、基础耗氧率和脂肪酸氧化。此外，CHIR-99021还可以降低肥胖患者肝细胞中脂滴大小和甘油三酯水平。结果表明，GSK 3抑制通过提高肥胖患者肝细胞中的线粒体功能来改善肝脂肪变性。肥胖患者脂肪干细胞来源的肝细胞显示肝脂肪变性肝脂肪变性伴随线粒体功能障碍线粒体功能障碍由低表达PGC-1α、TFAM和NRF 1 GSK 3抑制剂通过线粒体功能障碍调节人体代谢来改善肝脂肪变性;分子生物学
Obesity is an important risk factor and a potential treatment target for hepatic steatosis. The maladaptation of hepatic mitochondrial flexibility plays a key role in the hepatic steatosis. Herein, we found that hepatocyte-like cells derived from human adipose stem cell of obese patients exhibited the characteristics of hepatic steatosis and accompanied with lower expression of the subunits of mitochondrial complex I and lower oxidative phosphorylation levels. The GSK3 inhibitor CHIR-99021 promoted the expression of NDUFB8, NDUFB9, the subunits of mitochondrial complex I, the basal oxygen consumption rate, and the fatty acid oxidation of the hepatocytes of obese patients by upregulating the expression of the transcription factor PGC-1α, TFAM, and NRF1 involved in mitochondrial biogenesis. Moreover, CHIR-99021 decreased the lipid droplets size and the triglyceride levels in hepatocytes of obese patients. The results demonstrate that GSK3 inhibition ameliorates hepatic steatosis by elevating the mitochondrial function in hepatocytes of obese patients. Obese patients’ adipose-stem-cell-derived hepatocytes reveal hepatic steatosis Hepatic steatosis is accompanied the mitochondrial dysfunction The mitochondrial dysfunction is governed by the low expression PGC-1α, TFAM, and NRF1 GSK3 inhibitor ameliorates hepatic steatosis via mitochondrial dysfunction modulation human metabolism; molecular biology
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
82.9
作者：
Friedman SL;Neuschwander-Tetri BA;Rinella M;Sanyal AJ
通讯作者：
Sanyal AJ
影响因子：
6
作者：
Li H;Zhu L;Chen H;Li T;Han Q;Wang S;Yao X;Feng H;Fan L;Gao S;Boyd R;Cao X;Zhu P;Li J;Keating A;Su X;Zhao RC
通讯作者：
Zhao RC
影响因子：
4.9
作者：
Latorre, J.;Moreno-Navarrete, J. M.;Ortega, F. J.
通讯作者：
Ortega, F. J.
DOI：
10.1038/nrgastro.2017.32
发表时间：
2017-06
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
Gluchowski NL;Becuwe M;Walther TC;Farese RV Jr
通讯作者：
Farese RV Jr