MiR-203 is an anti-obese microRNA by targeting apical sodium-dependent bile acid transporter

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^*

来源：iScience, 2022, 25(8): 104708.

DOI：10.1016/j.isci.2022.104708

• DIET-INDUCED OBESITY
• INSULIN-RESISTANCE
• FAT
• EXPRESSION
• MIGRATION
• INVASION
• ADULTS
• LIVER
• MICE

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 rod its. miR-203 overexpression transgenic mice are resistant to high-fat diet (HFD)-induced obesity and dyslipide nia. 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.

• 单位
  y; 中国医学科学院; 哈尔滨医科大学