The Experts below are selected from a list of 255 Experts worldwide ranked by ideXlab platform
Alan F. Hofmann - One of the best experts on this subject based on the ideXlab platform.
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the enterohepatic circulation of Bile Acids in mammals form and functions
Frontiers in Bioscience, 2009Co-Authors: Alan F. HofmannAbstract:The features of the enterohepatic circulation of Bile Acids in mammals are reviewed. Inputs into the circulating Bile Acids are primary Bile Acids synthesized from cholesterol in the hepatocyte and secondary Bile Acids formed by bacterial modification of primary Bile Acids in the distal intestine. Intestinal conservation of Bile Acids generates pools of individual Bile Acids whose relative sizes determine biliary Bile acid composition. Efficient hepatic clearance results in low plasma Bile acid levels, and virtually no renal excretion. Methods for characterizing the enterohepatic circulation are summarized. Bile Acids have numerous physiological functions in the liver, biliary tract, and intestine resulting from their signaling and physicochemical properties.
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Bile Acids chemistry pathochemistry biology pathobiology and therapeutics
Cellular and Molecular Life Sciences, 2008Co-Authors: Alan F. Hofmann, Lee R HageyAbstract:Bile Acids and Bile alcohols in the form of their conjugates are amphipathic end products of cholesterol metabolism with multiple physiological functions. The great variety of Bile Acids and Bile alcohols that are present in vertebrates are tabulated. Bile salts have an enterohepatic circulation resulting from efficient vectorial transport of Bile salts through the hepatocyte and the ileal enterocyte; such transport leads to the accumulation of a pool of Bile salts that cycles between the liver and intestine. Bile salt anions promote lipid absorption, enhance tryptic cleavage of dietary proteins, and have antimicrobial effects. Bile salts are signaling molecules, activating nuclear receptors in the hepatocyte and ileal enterocyte, as well as an increasing number of G-protein coupled receptors. Bile Acids are used therapeutically to correct deficiency states, to decrease the cholesterol saturation of Bile, or to decrease the cytotoxicity of retained Bile Acids in cholestatic liver disease.
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how Bile Acids confer gut mucosal protection against bacteria
Proceedings of the National Academy of Sciences of the United States of America, 2006Co-Authors: Alan F. Hofmann, Lars EckmannAbstract:Bile is a complex mixture of organic and inorganic molecules that is stored in the gallbladder and released into the proximal small intestine when a meal is eaten. Bile is both an excretory secretion, to eliminate cholesterol, bilirubin, and waste products, and a digestive secretion, to promote lipid absorption. The dominant organic constituents of Bile are conjugated Bile Acids (also termed Bile salts), glycine or taurine N-acyl amidated derivatives of Bile Acids that are formed from cholesterol in the liver cell. Bile Acids are wedge-shaped, water soluble, amphipathic molecules with a hydrophobic side and a hydrophilic side. Adsorption of Bile acid anions to lipid bilayers of dietary membrane lipids or fatty Acids (derived by pancreatic lipase acting on triglyceride) increases the curvature of the bilayers, ultimately converting them to mixed micelles (1, 2). Such micellar solubilization of polar lipids greatly increases their rate of diffusion to the epithelial surface of the small intestine, and micellar solubilization is essential for the efficient absorption of lipids. Although most lipid absorption occurs in the proximal small intestine, conjugated Bile Acids themselves are not absorbed together with the solubilized lipids in the jejunum but pass to the distal small intestine, where they are efficiently absorbed by an active transport system present in the epithelium of the terminal ileum. Efficient intestinal reclamation of Bile Acids leads to the accumulation of a recycling pool of conjugated Bile Acids that circulates one or more times with each meal (3). Enterohepatic cycling of Bile Acids provides large quantities of Bile Acids for digestion.
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the continuing importance of Bile Acids in liver and intestinal disease
JAMA Internal Medicine, 1999Co-Authors: Alan F. HofmannAbstract:Bile Acids, the water-soluble, amphipathic end products of cholesterol metabolism, are involved in liver, biliary, and intestinal disease. Formed in the liver, Bile Acids are absorbed actively from the small intestine, with each molecule undergoing multiple enterohepatic circulations before being excreted. After their synthesis from cholesterol, Bile Acids are conjugated with glycine or taurine, a process that makes them impermeable to cell membranes and permits high concentrations to persist in Bile and intestinal content. The relation between the chemical structure and the multiple physiological functions of Bile Acids is reviewed. Bile Acids induce biliary lipid secretion and solubilize cholesterol in Bile, promoting its elimination. In the small intestine, Bile Acids solubilize dietary lipids promoting their absorption. Bile Acids are cytotoxic when present in abnormally high concentrations. This may occur intracellularly, as occurs in the hepatocyte in cholestasis, or extracellulary, as occurs in the colon in patients with Bile acid malabsorption. Disturbances in Bile acid metabolism can be caused by (1) defective biosynthesis from cholesterol or defective conjugation, (2) defective membrane transport in the hepatocyte or ileal enterocyte, (3) defective transport between organs or biliary diversion, and (4) increased bacterial degradation during enterohepatic cycling. Bile acid therapy involves Bile acid replacement in deficiency states or Bile acid displacement by ursodeoxycholic acid, a noncytotoxic Bile acid. In cholestatic liver disease, administration of ursodeoxycholic acid decreases hepatocyte injury by retained Bile Acids, improving liver tests, and slowing disease progression. Bile acid malabsorption may lead to high concentrations of Bile Acids in the colon and impaired colonic mucosal function; Bile acid sequestrants provide symptomatic benefit for diarrhea. A knowledge of Bile acid physiology and the perturbations of Bile acid metabolism in liver and digestive disease should be useful for the internist.
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A proposed nomenclature for Bile Acids
Journal of lipid research, 1992Co-Authors: Alan F. Hofmann, J. Sjövall, G. Kurz, A Radominska, C D Schteingart, G. S. Tint, Z. R. Vlahcevic, Kenneth D. R. SetchellAbstract:A proposal is made for a system of nomenclature of the more common unconjugated and conjugated Bile Acids. Acceptable trivial names for Bile Acids are tabulated, and guidelines are proposed for using these existing trivial names as roots to create acceptable semi-systematic names for other Bile Acids, as well as for new natural Bile Acids that will be discovered in the future. The term alpha-hyocholic is recommended to replace hyocholic, and beta-hyocholic to replace omega-muricholic. The term murideoxycholic acid is recommended for 3 alpha,6 beta-dihydroxy-5 beta-cholan-24-oic acid. Proposals are also made for Bile Acids with epimeric hydroxy groups, for unsaturated Bile Acids, and for Bile Acids with oxo- and/or hydroxy-oxo- substituents on the nucleus and/or on the side chain. For conjugated Bile Acids, the term "aminoacyl amidates" is recommended to replace "amidates" for Bile Acids conjugated in N-acyl linkage with amino Acids. Nomenclature for other types of conjugates (sulfates, glucuronides, glucosides) is included as well as abbreviations. It is recommended that the historic tradition of naming a newly discovered Bile acid after the species from which it was isolated be abandoned, and that in the future such a Bile acid should be named using the principles contained in this paper.
Ronald J.a. Wanders - One of the best experts on this subject based on the ideXlab platform.
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Bile Acids: the role of peroxisomes
Journal of lipid research, 2009Co-Authors: Sacha Ferdinandusse, Simone Denis, Phyllis L. Faust, Ronald J.a. WandersAbstract:It is well established that peroxisomes play a crucial role in de novo Bile acid synthesis. Studies in patients with a peroxisomal disorder have been indispensable for the elucidation of the precise role of peroxisomes. Several peroxisomal disorders are associated with distinct Bile acid abnormalities and each disorder has a characteristic pattern of abnormal Bile Acids that accumulate, which is often used for diagnostic purposes. The patients have also been important for determining the pathophysiological consequences of defects in Bile acid biosynthesis. In this review, we will discuss all the peroxisomal steps involved in Bile acid synthesis and the Bile acid abnormalities in patients with peroxisomal disorders. We will show the results of Bile acid measurements in several tissues from patients, including brain, and we will discuss the toxicity and the pathological effects of the abnormal Bile Acids.
Maryelizabeth Patti - One of the best experts on this subject based on the ideXlab platform.
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Bile Acids obesity and the metabolic syndrome
Best Practice & Research in Clinical Gastroenterology, 2014Co-Authors: Maryelizabeth PattiAbstract:Bile Acids are increasingly recognized as key regulators of systemic metabolism. While Bile Acids have long been known to play important and direct roles in nutrient absorption, Bile Acids also serve as signalling molecules. Bile acid interactions with the nuclear hormone receptor farnesoid X receptor (FXR) and the membrane receptor G-protein-coupled Bile acid receptor 5 (TGR5) can regulate incretin hormone and fibroblast growth factor 19 (FGF19) secretion, cholesterol metabolism, and systemic energy expenditure. Bile acid levels and distribution are altered in type 2 diabetes and increased following bariatric procedures, in parallel with reduced body weight and improved insulin sensitivity and glycaemic control. Thus, modulation of Bile acid levels and signalling, using Bile acid binding resins, TGR5 agonists, and FXR agonists, may serve as a potent therapeutic approach for the treatment of obesity, type 2 diabetes, and other components of the metabolic syndrome in humans.
Fredrik Backhed - One of the best experts on this subject based on the ideXlab platform.
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intestinal crosstalk between Bile Acids and microbiota and its impact on host metabolism
Cell Metabolism, 2016Co-Authors: Annika Wahlstrom, Hannsulrich Marschall, Sama I Sayin, Fredrik BackhedAbstract:The gut microbiota is considered a metabolic "organ" that not only facilitates harvesting of nutrients and energy from the ingested food but also produces numerous metabolites that signal through their cognate receptors to regulate host metabolism. One such class of metabolites, Bile Acids, is produced in the liver from cholesterol and metabolized in the intestine by the gut microbiota. These bioconversions modulate the signaling properties of Bile Acids via the nuclear farnesoid X receptor and the G protein-coupled membrane receptor 5, which regulate numerous metabolic pathways in the host. Conversely, Bile Acids can modulate gut microbial composition both directly and indirectly through activation of innate immune genes in the small intestine. Thus, host metabolism can be affected through microbial modifications of Bile Acids, which lead to altered signaling via Bile acid receptors, but also by altered microbiota composition.
Stephen R. Bloom - One of the best experts on this subject based on the ideXlab platform.
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Bile Acids and the metabolic syndrome
Annals of clinical biochemistry, 2019Co-Authors: Emma Rose Mcglone, Stephen R. BloomAbstract:Bile Acids have important roles in the regulation of lipid, glucose and energy metabolism. Metabolic diseases linked to obesity, including type 2 diabetes mellitus and non-alcoholic fatty liver disease, are associated with dysregulation of Bile acid homeostasis. Here, the basic chemistry and regulation of Bile Acids as well as their metabolic effects will be reviewed. Changes in circulating Bile Acids associated with obesity and related diseases will be reviewed. Finally, pharmaceutical manipulation of Bile acid homeostasis as therapy for metabolic diseases will be outlined.