文章基本信息

标题：MiR-203 is an anti-obese microRNA by targeting apical sodium-dependent bile acid transporter
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作者：Xin Liu ; Feiran Cheng ; Xue Bai 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：8
页码：1-24
DOI：10.1016/j.isci.2022.104708
语种：English
出版社：Elsevier
摘要：SummaryObesity 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.Graphical abstractDisplay OmittedHighlights•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 excretionHuman metabolism; Molecular biology