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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
High-fat diet aggravates colitis via mesenteric adipose tissue derived exosome metastasis-associated lung adenocarcinoma transcript 1
Dong Chen, Miao-Miao Lu, Jin-Hai Wang, Yue Ren, Ling-Ling Xu, Wei-Xin Cheng, Sai-Sai Wang, Xiao-Lin Li, Xiao-Fei Cheng, Jian-Guo Gao, Farhin Shaheed Kalyani, Xi Jin
Dong Chen, Jin-Hai Wang, Sai-Sai Wang, Xiao-Fei Cheng, Department of Colorectal Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Miao-Miao Lu, Yue Ren, Ling-Ling Xu, Wei-Xin Cheng, Farhin Shaheed Kalyani, Department of Medicine, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Xiao-Lin Li, Department of Emergency, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Jian-Guo Gao, Xi Jin, Department of Gastroenterology, The First affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Author contributions: Jin X designed the report; Chen D performed experiments and statistical analysis; Lu MM wrote the paper and assisted to design the report; Wang JH, Ren Y, Wang SS, Xu LL, Cheng XF, Cheng WX, Gao JG, and Li XL assisted to perform experiments and analyzed data; Kalyani FS assisted with paper writing; all authors had access to the study data and reviewed and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81770574; and the Natural Science Foundation of Zhejiang Province, No. LZ21H030002 and No. LY21H030005.
Institutional animal care and use committee statement: The study was reviewed and approved by the institutional review board of the Tab of Animal Experimental Ethical Inspection of the First Affiliated Hospital of Zhejiang University, NO. 2020-1101.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: All the data included in this study are available upon request by contact with the corresponding author.
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: Xi Jin, MD, PhD, Doctor, Professor, Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China.
jxfl007@zju.edu.cn
Received: December 4, 2021
Peer-review started: December 4, 2021
First decision: April 16, 2022
Revised: April 28, 2022
Accepted: July 6, 2022
Article in press: July 6, 2022
Published online: August 7, 2022
Processing time: 242 Days and 1.6 Hours
BACKGROUND
Obesity is associated with an increased risk of developing Crohn’s disease (CD), higher disease activity, and comparatively worse clinical outcomes.
AIM
To investigate the role of mesenteric adipose tissue-derived exosomes in the pathogenesis of CD aggravation in obese individuals.
METHODS
First, we induced colitis in mice initiated on high-fat and normal diets and compared the severity of colitis. We then extracted and identified exosomes from mesenteric adipose tissue and determined the levels of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in mesenteric adipose tissue-derived exosomes and the colon. Next, we demonstrated an interaction between MALAT1 and the miR-15a-5p/activating transcription factor 6 (ATF6) axis. Finally, we explored the effects of mesenteric adipose tissue-derived exosomes extracted from mice fed a high-fat or normal diet on the severity of 2,4,6-trinitrobe-nzenesulfonic acid (TNBS)-induced colitis and ATF6-related endoplasmic reticulum stress pathways.
RESULTS
High-fat diet was found to aggravate TNBS-induced colitis in mice. The expression of MALAT1 in mesenteric adipose tissue-derived exosomes of high-fat diet-fed mice increased. The increased expression of MALAT1 in colon tissue exacerbated TNBS-induced colitis and activated the ATF6 endoplasmic reticulum stress pathway. This effect was partially reversed by the reduced expression of MALAT1 and overexpression of miR-15a-5p.
CONCLUSION
Mesenteric adipose tissue-derived exosome-encapsulated long noncoding RNAs MALAT1 targets the colon and aggravates TNBS-induced colitis in obese mice, which may potentially act on the miR-15a-5p/ATF6 axis and activate endoplasmic reticulum stress.
Core Tip: A higher visceral adipose tissue ratio has been associated with increased disease activity in patients with Crohn’s disease. However, the mechanisms underlying this effect remain unclear. Our study indicates that a high-fat diet increases the mesenteric adipose tissue content and aggravates colitis in mice. Mesenteric adipose tissue-derived exosome long noncoding RNAs metastasis-associated lung adenocarcinoma transcript 1 can be absorbed by the colon, leading to the activation of the endoplasmic reticulum stress pathway by targeting the miR-15a-5p/activating transcription factor 6 axis to aggravate colitis.
