Hepatokine Fetuin B expression is regulated by leptin-STAT3 signalling and associated with leptin in obesity.
Hepatokine Fetuin B expression is regulated by leptin-STAT3 signalling and associated with leptin in obesity.
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肝因子胎球蛋白 B 表达受瘦素-STAT3 信号传导调节，并与肥胖中的瘦素相关
DOI：
10.1038/s41598-022-17000-w
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发表时间：
2022-07-27
影响因子：
4.6
通讯作者：
Li, Xuejun
中科院分区：
文献类型：
--
作者：
Wang, Dongmei;Wu, Menghua;Zhang, Xiaofang;Li, Long;Lin, Mingzhu;Shi, Xiulin;Zhao, Yan;Huang, Caoxin;Li, Xuejun
肥胖是一个日益扩大的全球公共卫生问题，也是代谢紊乱的主要原因。肝细胞因子Fetuin B参与调节胰岛素抵抗、糖代谢和肝脏脂肪变性。然而，胎球蛋白B激活的潜在机制仍不清楚。我们先前的基于人群的研究表明，在肥胖人群中，血清胎球蛋白B和体脂量之间存在显著相关性，这表明其在介导肥胖相关代谢紊乱中的潜力。在本研究中，我们进一步揭示了在肥胖人群中胎球蛋白B和瘦素之间的显著相关性，瘦素是由膨胀的脂肪组织释放的经典脂肪因子。一致地，在饮食诱导的肥胖小鼠中证实了升高的胎球蛋白B和瘦素水平。此外，体外研究表明，瘦素信号通路直接激活胎球蛋白B的转录和表达在原代肝细胞和AML 12细胞中的STAT 3依赖性的方式。STAT 3与FetuB启动子上的应答元件结合以直接激活FetuB转录。最后，通过对肥胖人群的中介作用分析，证实了胎球蛋白B在瘦素诱导的胰岛素抵抗中的中介作用。因此，我们的研究确定瘦素-STAT 3作为激活胎球蛋白B的上游信号通路，并为肥胖相关代谢紊乱的致病机制提供了新的见解。
Obesity is an expanding global public health problem and a leading cause of metabolic disorders. The hepatokine Fetuin B participates in regulating insulin resistance, glucose metabolism and liver steatosis. However, the mechanism underlying Fetuin B activation remains unclear. Our previous population-based study demonstrated a significant association between serum Fetuin B and body fat mass in an obese population, which indicates its potential in mediating obesity-related metabolic disorders. In the present study, we further revealed a significant correlation between Fetuin B and leptin, the classic adipokine released by expanding adipose tissue, in this obese population. Consistently, elevated Fetuin B and leptin levels were confirmed in diet-induced obese mice. Furthermore, an in vitro study demonstrated that the leptin signalling pathway directly activated the transcription and expression of Fetuin B in primary hepatocytes and AML12 cells in a STAT3-dependent manner. STAT3 binds to the response elements on FetuB promoter to directly activate FetuB transcription. Finally, the mediating effect of Fetuin B in insulin resistance induced by leptin was confirmed according to mediation analysis in this obese population. Therefore, our study identifies leptin-STAT3 as an upstream signalling pathway that activates Fetuin B and provides new insights into the pathogenic mechanisms of obesity-related metabolic disorders.
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影响因子：
7.7
作者：
Huynh FK;Levi J;Denroche HC;Gray SL;Voshol PJ;Neumann UH;Speck M;Chua SC;Covey SD;Kieffer TJ
通讯作者：
Kieffer TJ
DOI：
10.1186/1476-5926-2-s1-s12
发表时间：
2004-01-14
期刊：
Comparative hepatology
影响因子：
--
作者：
Ikejima K;Lang T;Zhang YJ;Yamashina S;Honda H;Yoshikawa M;Hirose M;Enomoto N;Kitamura T;Takei Y;Sato N
通讯作者：
Sato N
影响因子：
8.1
作者：
D'souza AM;Neumann UH;Glavas MM;Kieffer TJ
通讯作者：
Kieffer TJ
影响因子：
3.3
作者：
Andreoli, Angela;Garaci, Francesco;Guglielmi, Giuseppe
通讯作者：
Guglielmi, Giuseppe
Sparcl1 通过上调 CCL2 促进小鼠非酒精性脂肪性肝炎进展
影响因子：
15.9
作者：
Liu, Bin;Xiang, Liping;Lu, Yan
通讯作者：
Lu, Yan