Publication Name	World Journal of Gastroenterology
Manuscript ID	47797
Country	China

Received	2019-03-28 00:41
Peer-Review Started	2019-03-28 05:35
To Make the First Decision	2019-04-11 08:13
Return for Revision	2019-04-12 05:58
Revised	2019-05-07 09:13
Second Decision	2019-05-08 08:53
Accepted by Journal Editor-in-Chief
Accepted by Company Editor-in-Chief	2019-05-08 16:01
Articles in Press	2019-05-08 16:01
Publication Fee Transferred
Edit the Manuscript by Language Editor	2019-05-13 00:46
Typeset the Manuscript	2019-05-25 07:08
Publish the Manuscript Online	2019-05-28 09:29

ISSN	1007-9327 (print) and 2219-2840 (online)
Open Access	This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
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Category	Gastroenterology & Hepatology
Manuscript Type	Basic Study
Article Title	Trimethylamine N-oxide attenuates high-fat high-cholesterol diet-induced steatohepatitis by reducing hepatic cholesterol overload in rats
Manuscript Source	Unsolicited Manuscript
All Author List	Ze-Hua Zhao, Feng-Zhi Xin, Da Zhou, Ya-Qian Xue, Xiao-Lin Liu, Rui-Xu Yang, Qin Pan and Jian-Gao Fan
ORCID	Author(s) ORCID Number Ze-Hua Zhao http://orcid.org/0000-0002-3708-8881 Feng-Zhi Xin http://orcid.org/0000-0001-9674-0481 Da Zhou http://orcid.org/0000-0001-8838-1351 Ya-Qian Xue http://orcid.org/0000-0001-8641-8616 Xiao-Lin Liu http://orcid.org/0000-0003-4560-7589 Rui-Xu Yang http://orcid.org/0000-0001-9384-6408 Qin Pan http://orcid.org/0000-0001-5855-4952 Jian-Gao Fan http://orcid.org/0000-0001-7443-5056
Funding Agency and Grant Number	Funding Agency Grant Number National Key R and D Program of China 2017YFC0908903 National Natural Science Foundation of China 81873565 National Natural Science Foundation of China 81470840 National Natural Science Foundation of China 81800510 Shanghai Sailing Program 18YF1415900
Corresponding Author	Jian-Gao Fan, MD, PhD, Chief Doctor, Professor, Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kong Jiang Road, Shanghai 200092, China. fanjiangao@xinhuamed.com.cn
Key Words	Gut microbiota; Trimethylamine N-oxide; Nonalcoholic steatohepatitis; Endoplasmic reticulum stress; Cholesterol
Core Tip	The function of trimethylamine N-oxide (TMAO) in nonalcoholic steatohepatitis (NASH) remains unexplored. We investigate the effect of oral TMAO administration on the progression of NASH in a rat model induced by high-fat high-cholesterol (HFHC) diet. This study demonstrates for the first time that the gut microbial metabolite TMAO restores gut microbiota diversity, inhibits intestinal cholesterol absorption and reduces hepatic cholesterol overload, thus attenuating cholesterol-induced endoplasmic reticulum stress and hepatocyte cell death. These functions facilitate TMAO’s protection against HFHC diet-induced steatohepatitis in rats.
Publish Date	2019-05-28 09:29
Citation	Zhao ZH, Xin FZ, Zhou D, Xue YQ, Liu XL, Yang RX, Pan Q, Fan JG. Trimethylamine N-oxide attenuates high-fat high-cholesterol diet-induced steatohepatitis by reducing hepatic cholesterol overload in rats. World J Gastroenterol 2019; 25(20): 2450-2462
URL	https://www.wjgnet.com/1007-9327/full/v25/i20/2450.htm
DOI	https://dx.doi.org/10.3748/wjg.v25.i20.2450

Full Article (PDF)	WJG-25-2450.pdf
Full Article (Word)	WJG-25-2450.docx
The ARRIVE Guidelines	47797-The-ARRIVE-Guidelines-revision.pdf
Manuscript File	47797-Review_Edited.docx
Answering Reviewers	47797-Answering reviewers.pdf
Audio Core Tip	47797-Audio core tip.mp3
Biostatistics Review Certificate	47797-Biostatistics statement.pdf
Conflict-of-Interest Disclosure Form	47797-Conflict-of-interest statement.pdf
Copyright License Agreement	47797-Copyright license agreement.pdf
Approved Grant Application Form(s) or Funding Agency Copy of any Approval Document(s)	47797-Grant application form(s).pdf
Institutional Animal Care and Use Committee Approval Form or Document	47797-Institutional animal care and use committee statement.pdf
Institutional Review Board Approval Form or Document	47797-Institutional review board statement.pdf
Non-Native Speakers of English Editing Certificate	47797-Language certificate.pdf
Peer-review Report	47797-Peer-review(s).pdf
Scientific Misconduct Check	47797-Scientific misconduct check.pdf
Scientific Editor Work List	47797-Scientific editor work list.pdf