iScience (Aug 2022)

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

  • Xin Liu,
  • Feiran Cheng,
  • Xue Bai,
  • Tong Zhao,
  • Limin Zhao,
  • Lei Wang,
  • Mingqi Li,
  • Xianxian Wu,
  • Xiaohui Chen,
  • Pingping Tang,
  • Mengxue Wang,
  • Lintong Jiang,
  • Chaoqi Yan,
  • Fenghua Pei,
  • Xu Gao,
  • Ning Ma,
  • Baofeng Yang,
  • Yong Zhang

Journal volume & issue
Vol. 25, no. 8
p. 104708

Abstract

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Summary: 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.

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