The findings support the effects of BAs on satiety , lipid and cholesterol metabolism , incretins and glucose homoeostasis , energy metabolism , gut microbiota and endoplasmic reticulum stress following bariatric surgery .
Many of these metabolic effects are modulated through the BA receptors FXR and TGR5 .
We also explore a possible link between BAs and carcinogenesis following bariatric surgery .
Conclusions : Overall there is good evidence to support the role of BAs in the metabolic effects of bariatric surgery through the above mechanisms .
BAs could serve as a novel therapeutic pharmacological target for the treatment of obesity and its associated co-morbidities
Background : Bariatric surgery is currently the most efficacious treatment for obesity and its associated metabolic co-morbidities , such as diabetes .
The metabolic improvements occur through both weight-dependent and weight-independent mechanisms .
Bile acids ( BAs ) have emerged as key signalling molecules that have a central role in modulating many of the physiological effects seen after bariatric surgery .
This systematic review assesses the evidence from both human and animal studies for the role of BAs in reducing the metabolic complications of obesity following bariatric surgery .
Genomic analysis of hepatic farnesoid X receptor binding sites reveals altered binding in obesity and direct gene repression by farnesoid X receptor in mice.
UNLABELLED The nuclear bile acid receptor , farnesoid X receptor ( FXR ) , is an important transcriptional regulator of liver metabolism . Despite recent advances in underst and ing its functions , how FXR regulates genomic targets and whether the transcriptional regulation by FXR is altered in obesity remain largely unknown . Here , we analyzed hepatic genome-wide binding sites of FXR in healthy and dietary obese mice by chromatin immunoprecipitation sequencing ( ChIP-seq ) analysis . A total of 15,263 and 5,272 FXR binding sites were identified in livers of healthy and obese mice , respectively , after a short 1-hour treatment with the  synthetic FXR agonist , GW4064 . Of these sites , 7,440 and 2,344 were detected uniquely in healthy and obese mice .  FXR-binding sites were localized mostly in intergenic and intron regions at an inverted repeat 1 motif in both groups , but also clustered within 1 kilobase of transcription start sites . FXR-binding sites were detected near previously unknown target genes with novel functions , including diverse cellular signaling pathways , apoptosis , autophagy , hypoxia , inflammation , RNA processing , metabolism of amino acids , and transcriptional regulators . Further analyses of r and omly selected genes from both healthy and obese mice suggested that more FXR-binding sites are likely functionally inactive in obesity . Surprisingly , occupancies of FXR , retinoid X receptor alpha , RNA polymerase II , and epigenetic gene activation and repression histone marks , and messenger RNA levels of genes examined , suggested that direct gene repression by agonist-activated FXR is common . CONCLUSION Comparison of genomic FXR-binding sites in healthy and obese mice suggested that FXR transcriptional signaling is altered in dietary obese mice , which may underlie aberrant metabolism and liver function in obesity
The findings support the effects of BAs on satiety , lipid and cholesterol metabolism , incretins and glucose homoeostasis , energy metabolism , gut microbiota and endoplasmic reticulum stress following bariatric surgery .
Many of these metabolic effects are modulated through the BA receptors FXR and TGR5 .
We also explore a possible link between BAs and carcinogenesis following bariatric surgery .
Conclusions : Overall there is good evidence to support the role of BAs in the metabolic effects of bariatric surgery through the above mechanisms .
BAs could serve as a novel therapeutic pharmacological target for the treatment of obesity and its associated co-morbidities
Background : Bariatric surgery is currently the most efficacious treatment for obesity and its associated metabolic co-morbidities , such as diabetes .
The metabolic improvements occur through both weight-dependent and weight-independent mechanisms .
Bile acids ( BAs ) have emerged as key signalling molecules that have a central role in modulating many of the physiological effects seen after bariatric surgery .
This systematic review assesses the evidence from both human and animal studies for the role of BAs in reducing the metabolic complications of obesity following bariatric surgery .