Basic Study
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World J Gastroenterol. Aug 21, 2022; 28(31): 4328-4337
Published online Aug 21, 2022. doi: 10.3748/wjg.v28.i31.4328
Duodenal-jejunal bypass reduces serum ceramides via inhibiting intestinal bile acid-farnesoid X receptor pathway
Zhi-Qiang Cheng, Tong-Ming Liu, Peng-Fei Ren, Chang Chen, Yan-Lei Wang, Yong Dai, Xiang Zhang
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
Abstract
BACKGROUND

Bile acids play an important role in the amelioration of type 2 diabetes following duodenal-jejunal bypass (DJB). Serum bile acids are elevated postoperatively. However, the clinical relevance is not known. Bile acids in the peripheral circulation reflect the amount of bile acids in the gut. Therefore, a further investigation of luminal bile acids following DJB is of great significance.

AIM

To investigate changes of luminal bile acids following DJB.

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.

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 farnesoid X receptor (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.

CONCLUSION

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.

Keywords: Bariatric surgery; Duodenal-jejunal bypass; Farnesoid X receptor; Ceramide; Bile acids; Liver fat accumulation

Core Tip: Bile acids play an important role in the amelioration of type 2 diabetes following duodenal-jejunal bypass (DJB), and are elevated significantly in the serum postoperatively. Bile acids in the peripheral circulation reflect the amount of bile acids in the gut. Therefore, a further investigation of luminal bile acids following DJB is of great significance. Here we performed DJB in a high-fat diet/streptozotocin-induced diabetic rat model and demonstrated that DJB achieved rapid and durable improvement in glucose tolerance and led to increased total luminal bile acid concentrations with preferentially increased proportion of farnesoid X receptor (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 (chenodeoxycholic acid). There observations suggest a novel mechanism of bile acids in metabolic regulation after DJB.