MiR-203 is an anti-obese microRNA by targeting apical sodium-dependent bile acid transporter.
MiR-203 is an anti-obese microRNA by targeting apical sodium-dependent bile acid transporter.
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MiR-203 是一种抗肥胖 microRNA，靶向顶端钠依赖性胆汁酸转运蛋白
DOI：
10.1016/j.isci.2022.104708
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发表时间：
2022-08-19
期刊：
影响因子：
5.8
通讯作者：
Zhang, Yong
中科院分区：
文献类型：
--
作者：
Liu, Xin;Cheng, Feiran;Bai, Xue;Zhao, Tong;Zhao, Limin;Wang, Lei;Li, Mingqi;Wu, Xianxian;Chen, Xiaohui;Tang, Pingping;Wang, Mengxue;Jiang, Lintong;Yan, Chaoqi;Pei, Fenghua;Gao, Xu;Ma, Ning;Yang, Baofeng;Zhang, Yong
肥胖症的特征是体内脂肪沉积过多。胆汁酸（BA）是控制脂质吸收的重要调节剂。在这里，我们发现miR-203通过增加肥胖啮齿动物的总BA排泄来发挥减肥和降脂作用。miR-203过表达转基因小鼠对高脂饮食（HFD）诱导的肥胖和血脂异常具有抗性。此外，miR-203的敲低使代谢紊乱恶化。ASBT在调节BA稳态中起重要作用，并且是miR-203的直接靶点。在人肠上皮细胞中，miR-203的过表达通过抑制ASBT来降低细胞对BA的摄取。此外，TCF 7 L2在肥胖小鼠中下调，并作为miR-203的转录因子。ASBT mRNA水平与人群体质指数（BMI）呈正相关，而miR-203水平与BMI呈负相关。综上所述，这些数据表明miR-203可能是肥胖和血脂异常的新的治疗性BA调节剂。miR-203在肥胖啮齿动物和超重/肥胖人群中下调ASBT是肥胖症中miR-203的直接靶点TCF 7 L2在肥胖症中充当miR-203的上游激活剂miR-203通过增加TBA和脂质排泄来改善肥胖和血脂异常人类代谢;分子生物学
Obesity is characterized by excessive fat deposition within the body. Bile acids (BA) are important regulators for controlling the absorption of lipid. Here we show that miR-203 exerts weight-loss and lipid-lowering effects by increasing total BA excretion in obese rodents. miR-203 overexpression transgenic mice are resistant to high-fat diet (HFD)-induced obesity and dyslipidemia. Moreover, the knockdown of miR-203 deteriorates metabolic disorders. ASBT plays important role in regulating BA homeostasis and is a direct target of miR-203. In human intestinal epithelial cells, overexpression of miR-203 decreases the cellular uptake of BA by inhibiting ASBT. Furthermore, TCF7L2 is downregulated in obese mice and acts as a transcription factor of miR-203. The ASBT mRNA level was positively correlated with the body mass index (BMI) of population, while the miR-203 level was negatively associated with BMI. Taken together, these data suggest miR-203 could be a new therapeutic BA regulator for obesity and dyslipidemia. miR-203 is downregulated in obese rodents and overweight/obese population ASBT is a direct target of miR-203 in obesity TCF7L2 acts as an upstream activator of miR-203 in obesity miR-203 ameliorates obesity and dyslipidemia by increasing TBAs and lipids excretion Human metabolism; Molecular biology
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