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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2020; 26(18): 2203-2220
Published online May 14, 2020. doi: 10.3748/wjg.v26.i18.2203
Published online May 14, 2020. doi: 10.3748/wjg.v26.i18.2203
Folic acid attenuates high-fat diet-induced steatohepatitis via deacetylase SIRT1-dependent restoration of PPARα
Feng-Zhi Xin, Ze-Hua Zhao, Rui-Nan Zhang, Qin Pan, Chao Sun, Jian-Gao Fan, Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Zi-Zhen Gong, Jian-Gao Fan, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
Zi-Zhen Gong, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Zi-Zhen Gong, Department of Pediatric Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Author contributions: Xin FZ, Zhang RN, and Fan JG contributed to the experimental design; Xin FZ, Zhao ZH, Gong ZZ, and Sun C contributed to the acquisition and analysis of data; Fan JG and Zhang RN obtained the funding; and Xin FZ and Fan JG wrote the manuscript.
Supported by National Key R& D Program of China , No. 2017YFC0908903 ; National Natural Science Foundation of China , No. 81873565, No. 81470840, and No. 81700503 .
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of SHRM (SHRM-IACUC-015).
Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study.
Data sharing statement: No additional data are available.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Jian-Gao Fan, MD, PhD, Director, Professor, Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, 1665 Kongjiang Road, Shanghai 200092, China. fanjiangao@xinhuamed.com.cn
Received: December 31, 2019
Peer-review started: December 31, 2019
First decision: January 19, 2020
Revised: March 27, 2020
Accepted: April 17, 2020
Article in press: April 17, 2020
Published online: May 14, 2020
Processing time: 134 Days and 16.4 Hours
Peer-review started: December 31, 2019
First decision: January 19, 2020
Revised: March 27, 2020
Accepted: April 17, 2020
Article in press: April 17, 2020
Published online: May 14, 2020
Processing time: 134 Days and 16.4 Hours
Core Tip
Core tip: The roles of folic acid in hepatic lipid metabolism, hepatic one-carbon metabolism, and gut microbiota in high-fat diet (HFD)-induced steatohepatitis are still unknown. This study confirmed that folic acid ameliorated HFD-induced steatohepatitis by restoring PPARα levels via a SIRT1 dependent mechanism. Moreover, folic acid restored depleted hepatic one-carbon metabolism and the diversity of gut microbiota. All these findings further clarified the improvement effect of folic acid on HFD-induced steatohepatitis and suggested that folic acid may become a therapeutic drug to treat non-alcoholic fatty liver disease in the future.