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
Affiliations
- Xin Liu
- 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; Research Unit of Noninfectious Chronic Diseases in Frigid Zone, Chinese Academy of Medical Sciences, 2019RU070, Harbin 150081, China
- Feiran Cheng
- 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
- Xue Bai
- 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
- Tong Zhao
- 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
- Limin Zhao
- 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
- Lei Wang
- 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
- Mingqi Li
- 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
- Xianxian Wu
- 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
- Xiaohui Chen
- 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
- Pingping Tang
- 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
- Mengxue Wang
- 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
- Lintong Jiang
- 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
- Chaoqi Yan
- Department of Breast Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China
- Fenghua Pei
- Department of Gastroenterology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China
- Xu Gao
- Department of Biochemistry, College of Basic Medicine, Harbin Medical University, Harbin 150081, China
- Ning Ma
- Department of Biochemistry, College of Basic Medicine, Harbin Medical University, Harbin 150081, China
- Baofeng Yang
- 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; Department of Pharmacology and Therapeutics, Melbourne School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences University of Melbourne, Melbourne, VIC 3010, Australia; Research Unit of Noninfectious Chronic Diseases in Frigid Zone, Chinese Academy of Medical Sciences, 2019RU070, Harbin 150081, China; Corresponding author
- Yong Zhang
- 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; Research Unit of Noninfectious Chronic Diseases in Frigid Zone, Chinese Academy of Medical Sciences, 2019RU070, Harbin 150081, China; Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin 150081, China; Corresponding author
- Journal volume & issue
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Vol. 25,
no. 8
p. 104708
Abstract
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.