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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2016; 22(30): 6757-6763
Published online Aug 14, 2016. doi: 10.3748/wjg.v22.i30.6757
Mechanisms of triglyceride metabolism in patients with bile acid diarrhea
Nidhi Midhu Sagar, Michael McFarlane, Chuka Nwokolo, Karna Dev Bardhan, Ramesh Pulendran Arasaradnam
Nidhi Midhu Sagar, Michael McFarlane, School of Medicine, University of Warwick, Coventry CV4 7AL, United Kingdom
Michael McFarlane, Chuka Nwokolo, Ramesh Pulendran Arasaradnam, Department of Gastroenterology, University Hospitals Coventry and Warwickshire, Coventry CV2 2DX, United Kingdom
Karna Dev Bardhan, Department of Gastroenterology, Rotherham General Hospital NHS Trust, Rotherham S60 2UD, United Kingdom
Ramesh Pulendran Arasaradnam, Clinical Sciences Research Institute, University of Warwick, Coventry CV2 2DX, United Kingdom
Author contributions: Sagar NM and McFarlane M wrote the paper and analysed the data; Nwokolo C and Bardhan KD helped write the paper and provided project oversight; Arasaradnam RP co-ordinated the project, helped write the paper and analysed data.
Conflict-of-interest statement: The authors declare no conflict of interest.
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: Ramesh Arasaradnam, PhD, FRCP, FEBGH, Professor, Department of Gastroenterology, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, United Kingdom. r.arasaradnam@warwick.ac.uk
Telephone: +44-2476-966087 Fax: +44-2476-966090
Received: March 8, 2016
Peer-review started: March 10, 2016
First decision: May 12, 2016
Revised: May 28, 2016
Accepted: June 28, 2016
Article in press: June 28, 2016
Published online: August 14, 2016
Processing time: 148 Days and 22.1 Hours
Abstract

Bile acids (BAs) are essential for the absorption of lipids. BA synthesis is inhibited through intestinal farnesoid X receptor (FXR) activity. BA sequestration is known to influence BA metabolism and control serum lipid concentrations. Animal data has demonstrated a regulatory role for the FXR in triglyceride metabolism. FXR inhibits hepatic lipogenesis by inhibiting the expression of sterol regulatory element binding protein 1c via small heterodimer primer activity. Conversely, FXR promotes free fatty acids oxidation by inducing the expression of peroxisome proliferator-activated receptor α. FXR can reduce the expression of microsomal triglyceride transfer protein, which regulates the assembly of very low-density lipoproteins (VLDL). FXR activation in turn promotes the clearance of circulating triglycerides by inducing apolipoprotein C-II, very low-density lipoproteins receptor (VLDL-R) and the expression of Syndecan-1 together with the repression of apolipoprotein C-III, which increases lipoprotein lipase activity. There is currently minimal clinical data on triglyceride metabolism in patients with bile acid diarrhoea (BAD). Emerging data suggests that a third of patients with BAD have hypertriglyceridemia. Further research is required to establish the risk of hypertriglyceridaemia in patients with BAD and elicit the mechanisms behind this, allowing for targeted treatment.

Keywords: Bile acids; Bile acid diarrhea; Triglycerides; Farnesoid X receptor

Core tip: Bile acids are essential for the absorption of dietary lipids. The farnesoid X receptor (FXR) has a crucial role in triglyceride metabolism through regulating hepatic de novo lipogenesis and modulating free fatty acids oxidation and triglyceride clearance. There is a reported interruption of the metabolism of triglycerides in patients with bile acid diarrhoea (BAD) with a third of patients suffering with hypertriglyceridemia. Emerging treatments for BAD such as therapeutic imitation of the FXR may aid in alleviating symptoms and improving triglyceride levels.