Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2022; 28(25): 2937-2954
Published online Jul 7, 2022. doi: 10.3748/wjg.v28.i25.2937
Mechanism and therapeutic strategy of hepatic TM6SF2-deficient non-alcoholic fatty liver diseases via in vivo and in vitro experiments
Zu-Yin Li, Gang Wu, Chen Qiu, Zhi-Jie Zhou, Yu-Peng Wang, Guo-He Song, Chao Xiao, Xin Zhang, Gui-Long Deng, Rui-Tao Wang, Yu-Long Yang, Xiao-Liang Wang
Zu-Yin Li, Department of Hepatobiliary Surgery, Peking University People’s Hospital, Beijing 100034, China
Gang Wu, Department of Gastrointestinal Surgery, Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
Chen Qiu, Institute of Gallstone Disease, Shanghai East Hospital, Shanghai 200120, China
Zhi-Jie Zhou, Department of General Surgery, Huashan Hospital North, Shanghai 201907, China
Yu-Peng Wang, Guo-He Song, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Chao Xiao, Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200041, China
Xin Zhang, Xiao-Liang Wang, Department of General Surgery, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai 201700, China
Gui-Long Deng, Rui-Tao Wang, Department of General Surgery, Shanghai General Hospital, Shanghai 201600, China
Yu-Long Yang, Institute of Gallstone Disease, Center of Gallbladder Disease, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
Xiao-Liang Wang, Department of Hepatobiliary Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China
Author contributions: Li ZY and Wu G contributed equally to the work, Li ZY and Wu G performed the in vitro and in vivo experiments; Qiu C, Zhou ZJ, Wang YP, Song GH and Xiao C performed the analysis of GEO data; Deng GL and Wang RT provided the technical supports; Zhang X interpreted the data; Li ZY wrote the manuscript; Wang XL and Yang YL contributed equally, Wang XL and Yang YL conceived and supervised the study; all authors critically reviewed and edited the manuscript.
Supported by National Natural Science Foundation of China, No. 81670514 and No. 81702337; Scientific Research Project of Shanghai Municipal Health Commission, No. 202040065; and Natural Science Foundation of Shanghai Scientific and Technological Project of Innovative Action, No. 20ZR1411900.
Institutional review board statement: The study was reviewed and approved by the Shanghai First People's Hospital Institutional Review Board, No. 2016KY074.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Shanghai First People's Hospital, No. 2020-A0072-01.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data used and analyzed during the current study are available from the corresponding author on reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Liang Wang, PhD, Chief Doctor, Department of Hepatobiliary Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, No. 2800 Gongwei Road, Huinan Town, Pudong New Area, Shanghai 201399, China. xiaoliangwang2018@163.com
Received: December 21, 2021
Peer-review started: December 21, 2021
First decision: March 10, 2022
Revised: April 15, 2022
Accepted: May 22, 2022
Article in press: May 22, 2022
Published online: July 7, 2022
Core Tip

Core Tip: In this study, we observed TM6SF2 overexpression in nonalcoholic fatty liver disease (NAFLD) cases. TM6SF2 overexpression can reduce hepatic lipid accumulation, suggesting a protective role for TM6SF2 in a high-fat diet. Meanwhile, there is an imbalance in the processes of uptake, synthesis, and intracellular expense of fatty acids in TM6SF2-deficient mouse models. Therefore, we propose possible therapeutic strategies for NAFLD caused by TM6SF2 deficiency.