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Review
. 2016:2016:4390254.
doi: 10.1155/2016/4390254. Epub 2016 Feb 24.

Bile Acids, FXR, and Metabolic Effects of Bariatric Surgery

Olivier F Noel  1 , Christopher D Still  2 , George Argyropoulos  2 , Michael Edwards  3 , Glenn S Gerhard  3
Affiliations
Review

Bile Acids, FXR, and Metabolic Effects of Bariatric Surgery

Olivier F Noel et al. J Obes. 2016.

Abstract

Overweight and obesity represent major risk factors for diabetes and related metabolic diseases. Obesity is associated with a chronic and progressive inflammatory response leading to the development of insulin resistance and type 2 diabetes (T2D) mellitus, although the precise mechanism mediating this inflammatory process remains poorly understood. The most effective intervention for the treatment of obesity, bariatric surgery, leads to glucose normalization and remission of T2D. Recent work in both clinical studies and animal models supports bile acids (BAs) as key mediators of these effects. BAs are involved in lipid and glucose homeostasis primarily via the farnesoid X receptor (FXR) transcription factor. BAs are also involved in regulating genes involved in inflammation, obesity, and lipid metabolism. Here, we review the novel role of BAs in bariatric surgery and the intersection between BAs and immune, obesity, weight loss, and lipid metabolism genes.

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Figures

Figure 1
Figure 1
Major bile acids. The primary bile acids are synthesized from cholesterol in the liver. Secondary bile acids are formed by dehydroxylation of primary bile acids by intestinal bacteria. Primary and secondary bile acids can also undergo conjugation with taurine or glycine in the liver.
Figure 2
Figure 2
Mechanism of bile acid gene regulation. Bile acids can bind to the farnesoid X receptor (FXR) transcription factor which can regulate gene expression through binding to specific DNA motifs and can heterodimerize with retinoic X receptor-α (RXR-α) to regulate the expression of target genes.
Figure 3
Figure 3
Complement alternative activation pathway with corresponding receptors and mouse knockout phenotypes.
Figure 4
Figure 4
Subset of obesity and lipid associated genes that possess in silico identified FXR motifs.
See this image and copyright information in PMC

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