Cheng ZQ, Liu TM, Ren PF, Chen C, Wang YL, Dai Y, Zhang X. Duodenal-jejunal bypass reduces serum ceramides via inhibiting intestinal bile acid-farnesoid X receptor pathway. World J Gastroenterol 2022; 28(31): 4328-4337 [PMID: 36159007 DOI: 10.3748/wjg.v28.i31.4328]
Corresponding Author of This Article
Xiang Zhang, MD, PhD, Surgeon, Surgical Oncologist, Department of General Surgery, Qilu Hospital of Shandong University, No. 107 West Wenhua Road, Jinan 250012, Shandong Province, China. xiang.zhang02@hotmail.com
Research Domain of This Article
Surgery
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
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/
Zhi-Qiang Cheng, Chang Chen, Yan-Lei Wang, Yong Dai, Xiang Zhang, Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Tong-Ming Liu, Department of Colorectal and Anal Surgery, Feicheng Hospital Affiliated to Shandong First Medical University, Feicheng 271600, Shandong Province, China
Peng-Fei Ren, Department of General Surgery, Lincheng People’s Hospital, Dezhou 253500, Shandong Province, China
Author contributions: Cheng ZQ and Liu TM were involved in animal surgery, data collection, interpretation, statistical analysis, and writing of the manuscript; Ren PF, Chen C, Wang YL and Dai Y were involved in animal surgery, experimental analysis and assist in writing; Cheng ZQ, Dai Y and Zhang X were involved in conception, design, and coordination of the work; Dai Y and Zhang X are the guarantors of this work; and all authors critically reviewed the manuscript and have approved the publication of this final version of the manuscript.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Ethics Committee on Animal Experiment of Shandong University Qilu Hospital (KYLL-2017(ZM)-156).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiang Zhang, MD, PhD, Surgeon, Surgical Oncologist, Department of General Surgery, Qilu Hospital of Shandong University, No. 107 West Wenhua Road, Jinan 250012, Shandong Province, China. xiang.zhang02@hotmail.com
Received: March 11, 2022 Peer-review started: March 11, 2022 First decision: May 10, 2022 Revised: May 12, 2022 Accepted: July 25, 2022 Article in press: July 25, 2022 Published online: August 21, 2022 Processing time: 158 Days and 10.8 Hours
ARTICLE HIGHLIGHTS
Research background
Bile acids have proved to be signaling molecules in mediating metabolic benefits and circulating bile acids were found to be increased following duodenal-jejunal bypass (DJB). However, whether and how the bile acids take effect in the amelioration of metabolic disorders after DJB remain unknown.
Research motivation
Circulating bile acids reflect the amount of bile acids within the gut. It has been proved that luminal bile acids take effect via Takeda G-protein-coupled receptor 5 and nuclear farnesoid X receptor (FXR). However, different subtypes of bile acids have distinct effect on the downstream pathway of FXR and hence, a further investigation of luminal bile acids after DJB is of great significance.
Research objectives
To investigate changes and mechanisms of luminal bile acids in mediating metabolic benefits following DJB.
Research methods
Salicylhydroxamic acid (SHAM), DJB, and DJB with oral chenodeoxycholic acid (CDCA) supplementation were performed in a high-fat-diet/streptozotocin-induced diabetic rat model. Body weight, energy intake, oral glucose tolerance test, luminal bile acids, serum ceramides and intestinal ceramide synthesis were analyzed at week 12 postoperatively.
Research results
Compared to SHAM, DJB achieved rapid and durable improvement in glucose tolerance and led to increased total luminal bile acid concentrations with preferentially increased proportion of FXR - inhibitory bile acids within the common limb. Intestinal ceramide synthesis was repressed with decreased serum ceramides, and this phenomenon could be partially antagonized by luminal supplementation of FXR activating bile acid CDCA.
Research conclusions
DJB significantly changes luminal bile acid composition with increased proportion FXR-inhibitory bile acids and reduces serum ceramide levels. There observations suggest a novel mechanism of bile acids in metabolic regulation after DJB.
Research perspectives
Mechanisms of bile acids in mediating metabolic benefits after bariatric surgery.
