Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jul 10, 2016; 7(13): 260-270
Published online Jul 10, 2016. doi: 10.4239/wjd.v7.i13.260
Role of bile acids in the regulation of the metabolic pathways
Hiroki Taoka, Yoko Yokoyama, Kohkichi Morimoto, Naho Kitamura, Tatsuya Tanigaki, Yoko Takashina, Kazuo Tsubota, Mitsuhiro Watanabe
Hiroki Taoka, Tatsuya Tanigaki, Department of Environmental Information, Keio University, Fujisawa, Kanagawa 252-0882, Japan
Yoko Yokoyama, Naho Kitamura, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa 252-0882, Japan
Kohkichi Morimoto, Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Yoko Takashina, Research Institute of SFC, Keio University, Fujisawa, Kanagawa 252-0882, Japan
Kazuo Tsubota, Department of Ophthalmology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Mitsuhiro Watanabe, Graduate School of Media and Governance, Department of Environment and Information Studies, Keio University, Fujisawa, Kanagawa 252-0882, Japan
Mitsuhiro Watanabe, Department of Internal Medicine, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan
Author contributions: Taoka H, Watanabe M devised the study concept and design; Taoka H, Yokoyama Y, Morimoto K, Watanabe M searched the literature; Taoka H, Yokoyama Y, Morimoto K, Kitamura N, Watanabe M drafted the article; all authors revised the article for important intellectual content; Watanabe M gave final approval for the article.
Conflict-of-interest statement: No potential conflicts of interest. No financial support.
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/
Correspondence to: Mitsuhiro Watanabe, PhD, Professor of Graduate School of Media and Governance, Professor of Faculty of Environment and Information Studies, Graduate School of Media and Governance, Department of Environment and Information Studies, Keio University, tau42, 5322 Endo, Fujisawa, Kanagawa 252-0882, Japan. wmitsu@sfc.keio.ac.jp
Telephone: +81-466-493516 Fax: +81-466-493516
Received: October 1, 2015
Peer-review started: October 9, 2015
First decision: November 6, 2015
Revised: November 24, 2015
Accepted: May 17, 2016
Article in press: May 27, 2016
Published online: July 10, 2016
Processing time: 278 Days and 19 Hours
Abstract

Recent studies have revealed that bile acids (BAs) are not only facilitators of dietary lipid absorption but also important signaling molecules exerting multiple physiological functions. Some major signaling pathways involving the nuclear BAs receptor farnesoid X receptor and the G protein-coupled BAs receptor TGR5/M-BAR have been identified to be the targets of BAs. BAs regulate their own homeostasis via signaling pathways. BAs also affect diverse metabolic pathways including glucose metabolism, lipid metabolism and energy expenditure. This paper suggests the mechanism of controlling metabolism via BA signaling and demonstrates that BA signaling is an attractive therapeutic target of the metabolic syndrome.

Keywords: Bile acids; TGR5/M-BAR; Farnesoid X receptor; Glucose metabolism; Energy metabolism; Lipid metabolism; Bariatric surgery; Microbiota; Incretin; Bile acid binding resin

Core tip: Bile acids (BAs) are important molecules that participate in various metabolic pathways. BA signaling mechanisms are attractive therapeutic targets of the metabolic syndrome. In this review, we show the mechanisms of controlling glucose, lipid and energy metabolism via BA signaling. Furthermore, the authors also describe how those basic scientific studies have been applied to the clinical setting. Particularly, bile acid binding resin (BABR) originally used to treat hypercholesterolemia also stimulates incretin secretion and improves glucose metabolism. In addition to BABR, the clinical application of farnesoid X receptor and TGR5/M-BAR agonists are ongoing for the treatment of metabolic syndrome. The effects of bariatric surgery on glycemic control are also associated with BA metabolism.