Bile Acid Metabolism and Signaling
TLDR
Enterohepatic circulation of bile acids from the liver to intestine and back to the liver plays a central role in nutrient absorption and distribution, and metabolic regulation and homeostasis.Abstract:
Bile acids are important physiological agents for intestinal nutrient absorption and biliary secretion of lipids, toxic metabolites, and xenobiotics. Bile acids also are signaling molecules and metabolic regulators that activate nuclear receptors and G protein-coupled receptor (GPCR) signaling to regulate hepatic lipid, glucose, and energy homeostasis and maintain metabolic homeostasis. Conversion of cholesterol to bile acids is critical for maintaining cholesterol homeostasis and preventing accumulation of cholesterol, triglycerides, and toxic metabolites, and injury in the liver and other organs. Enterohepatic circulation of bile acids from the liver to intestine and back to the liver plays a central role in nutrient absorption and distribution, and metabolic regulation and homeostasis. This physiological process is regulated by a complex membrane transport system in the liver and intestine regulated by nuclear receptors. Toxic bile acids may cause inflammation, apoptosis, and cell death. On the other hand, bile acid-activated nuclear and GPCR signaling protects against inflammation in liver, intestine, and macrophages. Disorders in bile acid metabolism cause cholestatic liver diseases, dyslipidemia, fatty liver diseases, cardiovascular diseases, and diabetes. Bile acids, bile acid derivatives, and bile acid sequestrants are therapeutic agents for treating chronic liver diseases, obesity, and diabetes in humans.read more
Citations
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Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis.
TL;DR: The mechanistic links between bile acids and gastrointestinal carcinogenesis in CRC and HCC are discussed, which involve two major bile acid-sensing receptors, farnesoid X receptor (FXR) and G protein-coupled bile Acid receptor 1 (TGR5).
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The gut–liver axis and the intersection with the microbiome
Anupriya Tripathi,Anupriya Tripathi,Justine W. Debelius,David A. Brenner,Michael Karin,Rohit Loomba,Bernd Schnabl,Bernd Schnabl,Rob Knight +8 more
TL;DR: Gut–liver communications in liver disease is reviewed, exploring the molecular, genetic and microbiome relationships and discussing prospects for exploiting the microbiome to determine liver disease stage and to predict the effects of pharmaceutical, dietary and other interventions at a population and individual level.
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Bile Acid Signaling in Metabolic Disease and Drug Therapy
Tiangang Li,John Y.L. Chiang +1 more
TL;DR: An interaction of liver bile acids and gut microbiota in the regulation of liver metabolism and potential therapeutic agents for treating metabolic diseases of the liver are revealed.
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Mechanisms and disease consequences of nonalcoholic fatty liver disease
TL;DR: In this paper, the authors provide an in-depth discussion of the underlying pathogenetic mechanisms that lead to progressive liver injury, including the metabolic origins of NAS, the effect of NAFLD on hepatic glucose and lipid metabolism, bile acid toxicity, macrophage dysfunction, and hepatic stellate cell activation, and consider the role of genetic, epigenetic and environmental factors that promote fibrosis progression and risk of hepatocellular carcinoma in NASH.
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Metabolomics for Investigating Physiological and Pathophysiological Processes
TL;DR: How metabolomics is yielding important new insights into a number of important biological and physiological processes is explored, with a major focus on illustrating how metabolomics and discoveries made through metabolomics are improving the understanding of both normal physiology and the pathophysiology of many diseases.
References
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TL;DR: This research was supported by grants from the National Institutes of Health (HL20948) and the Perot Family Foundation.
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Identification of a Nuclear Receptor for Bile Acids
Makoto Makishima,Arthur Y. Okamoto,Joyce J. Repa,Hua Tu,R. Marc Learned,Alvin Luk,Mitchell V. Hull,Kevin D. Lustig,David J. Mangelsdorf,Bei Shan +9 more
TL;DR: Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor, which demonstrates a mechanism by which bile acid transcriptionally regulate their biosynthesis and enterohepatic transport.