Bile Acids in Physiology, Pathology and Pharmacology

Abstract

Bile acids, synthesized by hepatocytes from cholesterol, are specific and quantitatively important organic components of bile, where they are the main driving force of the osmotic process that generates bile flow toward the canaliculus. The bile acid pool comprises a variety of species of amphipathic acidic steroids. They are not mere detergent molecules that play a key role in fat digestion and the intestinal absorption of hydrophobic compounds present in the intestinal lumen after meals, including liposoluble vitamins. They are now known to be involved in the regulation of multiple functions in liver cells, mainly hepatocytes and cholangiocytes, and also in extrahepatic tissues. The identification of nuclear receptors, such as farnesoid X receptor (FXR or NR1H4), and plasma membrane receptors, such as the G protein-coupled bile acid receptor (TGR5, GPBAR1 or MBAR), which are able to trigger specific and complex responses upon activation (with dissimilar sensitivities) by different bile acid molecular species and synthetic agonists, has opened a new and promising field of research whose implications extend to physiology, pathology and pharmacology. In addition, pharmacological development has taken advantage of advances in the understanding of the chemistry and biology of bile acids and the biological systems that interact with them, which in addition to the receptors include several families of transporters and export pumps, to generate novel bile acid derivatives aimed at treating different liver diseases, such as cholestasis, biliary diseases, metabolic disorders and cancer. This review is an update of the role of bile acids in health and disease.

The Lactobacillus Bile Salt Hydrolase Repertoire Reveals Niche-Specific Adaptation

“…Bile acids are synthesized by the liver from cholesterol and are essential for lipoprotein, glucose, drug, and energy metabolism ( 1 , 2 ). Primary bile acids are made by the host and make their way through the small intestine, where 95% of bile acids are absorbed in the terminal ileum through the activity of the enterohepatic system ( 3 ). The remaining 5% that enter the large intestine can be modified by members of the gut microbiota to form secondary bile acids ( 4 ).…”

“…The remaining 5% that enter the large intestine can be modified by members of the gut microbiota to form secondary bile acids ( 4 ). Bile acids function to emulsify bile lipids such as cholesterol, facilitating adsorption into the bloodstream through the intestinal epithelium ( 3 ). In addition to facilitating adsorption of fats and cholesterol, bile acids can directly shape host physiology in a variety of ways, including acting as signaling molecules for the nuclear receptor farnesoid X receptor (FXR) ( 5 , 6 ) and the G-protein-coupled TGR5 receptor ( 7 ).…”

Cross-Species Molecular Imaging of Bile Salts and Lipids in Liver: Identification of Molecular Structural Markers in Health and Disease

“…During the past two decades, bile salts have been upgraded from molecules required for absorption of dietary lipids and fat-soluble vitamins, to signaling molecules regulating biological processes as diverse as nutrient metabolism, inflammation, and liver regeneration. 1 − 4 The discovery of bile salt receptors that mediate these signaling activities was key to the renewed interest in bile salts by academic and pharmaceutical communities. In particular, Farnesoid-X Receptor (FXR), a bile salt-activated transcription factor with an essential role in bile salt homeostasis, has been studied extensively.…”

Plasma Membrane Transporters as Biomarkers and Molecular Targets in Cholangiocarcinoma

“…The latter ones are of particular interest as biomarkers, since they may permit to distinguish different types of tumors based on the organ or the cell type from where they are originated (Table 1). Regarding the liver, transport proteins involved in the uptake and efflux of bile acids [3] meet these requirements and have been proposed as biomarkers [4]. This is the case of the apical sodium-dependent bile acid transporter (ASBT, gene symbol SLC10A2), located in the apical membrane of cholangiocytes, whose expression is maintained or slightly increased in CCA [5].…”