HuR promotes triglyceride synthesis and intestinal fat absorption

Cihang Liu; Yunping Lin; Ying Wang; Shuyong Lin; Jing Zhou; Hao Tang; Xia Yi; Zhengliang Ma; Tianjiao Xia; Bin Jiang; Feng Tian; Zhenyu Ju; Baohua Liu; Xiaoping Gu; Zhongzhou Yang; Wengong Wang

doi:10.1016/j.celrep.2024.114238

HuR promotes triglyceride synthesis and intestinal fat absorption

Cell Rep. 2024 May 28;43(5):114238. doi: 10.1016/j.celrep.2024.114238. Epub 2024 May 14.

Authors

Cihang Liu¹, Yunping Lin², Ying Wang², Shuyong Lin³, Jing Zhou³, Hao Tang⁴, Xia Yi², Zhengliang Ma⁵, Tianjiao Xia⁶, Bin Jiang², Feng Tian⁷, Zhenyu Ju⁸, Baohua Liu⁹, Xiaoping Gu¹⁰, Zhongzhou Yang¹¹, Wengong Wang¹²

Affiliations

¹ Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China.
² Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China.
³ State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
⁴ National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine, Heart Center of Henan Provincial People's Hospital, Central China Fuwai Hospital of Zhengzhou University, Central China Fuwai Hospital and Central China Branch of National Center for Cardiovascular Diseases, Zhengzhou, Henan 450003, China.
⁵ Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
⁶ Medical School, Nanjing University, Nanjing 210093, China.
⁷ Department of Laboratory Animal Science, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China.
⁸ Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou 510632, China.
⁹ Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Carson International Cancer Center, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen 518060, China.
¹⁰ Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China. Electronic address: xiaopinggu@nju.edu.cn.
¹¹ Medical School, Nanjing University, Nanjing 210093, China. Electronic address: zhongzhouyang@nju.edu.cn.
¹² Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China; Center for Healthy Aging, Changzhi Medical College, Changzhi 046000, China; Liaoning Technology and Engineering Center for Tumor Immunology and Molecular Theranostics, Collaborative Innovation Center for Age-related Disease, Life Science Institute of Jinzhou Medical University, Jinzhou 121001, Liaoning, China. Electronic address: wwg@bjmu.edu.cn.

PMID: 38748875
DOI: 10.1016/j.celrep.2024.114238

Abstract

Triacylglyceride (TAG) synthesis in the small intestine determines the absorption of dietary fat, but the underlying mechanisms remain to be further studied. Here, we report that the RNA-binding protein HuR (ELAVL1) promotes TAG synthesis in the small intestine. HuR associates with the 3' UTR of Dgat2 mRNA and intron 1 of Mgat2 pre-mRNA. Association of HuR with Dgat2 3' UTR stabilizes Dgat2 mRNA, while association of HuR with intron 1 of Mgat2 pre-mRNA promotes the processing of Mgat2 pre-mRNA. Intestinal epithelium-specific HuR knockout reduces the expression of DGAT2 and MGAT2, thereby reducing the dietary fat absorption through TAG synthesis and mitigating high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and obesity. Our findings highlight a critical role of HuR in promoting dietary fat absorption.

Keywords: CP: Metabolism; CP: Molecular biology; DGAT2; HuR; MGAT2; intestinal triglyceride synthesis.

MeSH terms

3' Untranslated Regions / genetics
Acyltransferases
Animals
Diacylglycerol O-Acyltransferase / genetics
Diacylglycerol O-Acyltransferase / metabolism
Diet, High-Fat* / adverse effects
Dietary Fats / metabolism
Dietary Fats / pharmacology
ELAV-Like Protein 1* / genetics
ELAV-Like Protein 1* / metabolism
Humans
Intestinal Absorption*
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Non-alcoholic Fatty Liver Disease / genetics
Non-alcoholic Fatty Liver Disease / metabolism
Non-alcoholic Fatty Liver Disease / pathology
Obesity / genetics
Obesity / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
Triglycerides* / biosynthesis
Triglycerides* / metabolism

Substances

Triglycerides
ELAV-Like Protein 1
Diacylglycerol O-Acyltransferase
Elavl1 protein, mouse
RNA, Messenger
Dietary Fats
2-acylglycerol O-acyltransferase
3' Untranslated Regions
Acyltransferases