Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2023; 29(21): 3280-3291
Published online Jun 7, 2023. doi: 10.3748/wjg.v29.i21.3280
Fibroblast growth factor 15, induced by elevated bile acids, mediates the improvement of hepatic glucose metabolism after sleeve gastrectomy
Meng Wei, Wei-Bo Cao, Ru-Dong Zhao, Dan-Ping Sun, Yi-Ze Liang, Ya-Di Huang, Ze-Wei Cheng, Jun Ouyang, Wen-Shuo Yang, Wen-Bin Yu
Meng Wei, Wei-Bo Cao, Ru-Dong Zhao, Dan-Ping Sun, Yi-Ze Liang, Ya-Di Huang, Ze-Wei Cheng, Jun Ouyang, Wen-Shuo Yang, Wen-Bin Yu, Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Author contributions: Wei M and Yu WB contributed to conception and design of research; Wei M, Sun DP, Yang WS, Cao WB, and Zhao RD contributed to performed experiments; Wei M, Liang YZ, and Cheng ZW analyzed data; Wei M, Sun DP, Liang YZ, and Ouyang J prepared figures; Wei M, Huang YD, and Sun DP drafted manuscript; Wei M, Liang YZ, and Yu WB edited and revised manuscript; Wei M, Sun DP, Cao WB, Zhao RD, Liang YZ, Huang YD, Cheng ZW, Ouyang J, Yang WS, and Yu WB approved final version of manuscript.
Supported by the National Natural Science Foundation of China, No. 81600617.
Institutional review board statement: The study was reviewed and approved by the laboratory animal ethical and welfare committee of Shandong University Cheeloo College of Medicine Institutional Review Board (Approval No. 19200).
Conflict-of-interest statement: The authors declare that they have no competing interests.
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:
Corresponding author: Wen-Bin Yu, MD, PhD, Chief Doctor, Professor, Department of General Surgery, Qilu Hospital of Shandong University, No. 107 Wenhua Xi Road, Jinan 250012, Shandong Province, China.
Received: March 6, 2023
Peer-review started: March 6, 2023
First decision: March 18, 2023
Revised: March 31, 2023
Accepted: May 8, 2023
Article in press: May 8, 2023
Published online: June 7, 2023
Research background

Bariatric surgery can significantly ameliorate type 2 diabetes mellitus (T2DM) through its rapid and durable weight-loss and hypoglycemic action. Both biles acids (BAs) and fibroblast growth factor (FGF) 15/19 are increased after surgery. Whether BAs and FGF15/19 participates in amelioration of T2DM after bariatric surgery and the underlying mechanism remain incompletely illuminated.

Research motivation

FGF15 which is induced by farnesoid X receptor (FXR) in ileum can improve the hepatic glucose metabolism through entero-hepatic circulation. Our previous study confirms that BA profiles within peripheral circulation and portal vein have changed after SG, with significant increase of FXR- activated BAs levels.

Research objectives

This study aimed to evaluate the effect of FGF15 on improvement of T2DM triggered by elevated BAs after sleeve gastrectomy (SG) and investigate the underlying mechanism.

Research methods

The weight-loss and hypoglycemic action of SG were detected in a diabetic rat model induced by High-fat diet and streptozotocin (STZ), as well as the hepatic glycogen content and gluconeogenesis activity. Total BA (TBA) together with the FXR-agonistic BA subspecies levels in systemic serum and portal vein were examined at week 12 post-surgery. Then the expression and activity of ileal FXR and FGF15 and hepatic FGFR4 with its corresponding signal pathways involved in glucose metabolism were detected.

Research results

Compared with SHAM group, SG induced sustained weight loss and improved the hepatic glucose metabolism by promoting hepatic glycogen synthesis and inhibiting the gluconeogenesis. TBA levels and the FXR-agonistic subspecies in serum and portal vein were elevated after SG. Consequently, the ileal expression of FXR and FGF15 were also advanced. Moreover, the hepatic expression of FGFR4 and the activities of its corresponding pathways were stimulated in SG-operated rats.

Research conclusions

FGF15, triggered by elevated BAs after SG, acts as an endocrine factor to induce the improvement of hepatic glucose metabolism through the intestine-liver crosstalk.

Research perspectives

FXR-agonistic BA subspecies and FGF15 participate in improvement of hepatic glucose metabolism, and may be developed as new targets for the treatment of T2DM.