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

doi:10.1016/j.isci.2022.104708

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

iScience. 2022 Jul 2;25(8):104708. doi: 10.1016/j.isci.2022.104708. eCollection 2022 Aug 19.

Authors

Xin Liu^{1

2}, Feiran Cheng¹, Xue Bai¹, Tong Zhao¹, Limin Zhao¹, Lei Wang¹, Mingqi Li¹, Xianxian Wu¹, Xiaohui Chen¹, Pingping Tang¹, Mengxue Wang¹, Lintong Jiang¹, Chaoqi Yan³, Fenghua Pei⁴, Xu Gao⁵, Ning Ma⁵, Baofeng Yang^{1

6

2}, Yong Zhang^{1

2

7}

Affiliations

¹ Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China.
² Research Unit of Noninfectious Chronic Diseases in Frigid Zone, Chinese Academy of Medical Sciences, 2019RU070, Harbin 150081, China.
³ Department of Breast Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
⁴ Department of Gastroenterology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
⁵ Department of Biochemistry, College of Basic Medicine, Harbin Medical University, Harbin 150081, China.
⁶ Department of Pharmacology and Therapeutics, Melbourne School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences University of Melbourne, Melbourne, VIC 3010, Australia.
⁷ Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin 150081, China.

Abstract

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.

Keywords: human metabolism; molecular biology.