Cited by 935Drug Transport and Resistance MechanismsCholesterol and Lipid MetabolismGut microbiota and health

Bile acid signaling in metabolic disease and drug therapy

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Li, Tiangang, Chiang, John Y.L.·2014·Pharmacological Reviews

Abstract

Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates hepatobiliary secretion of lipids, lipophilic metabolites, and xenobiotics. In the intestine, bile acids are essential for the absorption, transport, and metabolism of dietary fats and lipid-soluble vitamins. Extensive research in the last 2 decades has unveiled new functions of bile acids as signaling molecules and metabolic integrators. The bile acid-activated nuclear receptors farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, and G protein-coupled bile acid receptor play critical roles in the regulation of lipid, glucose, and energy metabolism, inflammation, and drug metabolism and detoxification. Bile acid synthesis exhibits a strong diurnal rhythm, which is entrained by fasting and refeeding as well as nutrient status and plays an important role for maintaining metabolic homeostasis. Recent research revealed an interaction of liver bile acids and gut microbiota in the regulation of liver metabolism. Circadian disturbance and altered gut microbiota contribute to the pathogenesis of liver diseases, inflammatory bowel diseases, nonalcoholic fatty liver disease, diabetes, and obesity. Bile acids and their derivatives are potential therapeutic agents for treating metabolic diseases of the liver.

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Crossref · 10.1124/pr.113.008201

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  • Secondary bile acids antagonize the nuclear membrane farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5 in the intestines.

    “Secondary bile acids antagonize the nuclear membrane farnesoid X receptor (FXR) and the G protein–coupled receptor TGR5103 in the intestines.”

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Authors
Li, T., & Chiang, J. Y. L.
Affiliations
University of Kansas Medical Center (US)
Venue
Pharmacological Reviews
Publisher
Elsevier BV
Published
2014-10
Volume
66
Issue
4
Pages
948-983
ISSN
0031-6997 (ISSN-L)
OpenAlex
W2123561714
Cited by
935
References
435
Citations by year
2026: 82 · 2025: 73 · 2024: 93 · 2023: 89 · 2022: 117 · 2021: 88 · 2020: 95 · 2019: 81 · 2018: 71 · 2017: 74 · 2016: 39 · 2015: 26 · 2014: 7
FWCI
5.53
Type
journal article
Language
en
Open access
Locations
  • Pharmacological Reviews (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01dk044442-26, DK58379, DK44442)
  • National Institute of General Medical Sciences (P20GM103549)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 58379, DK44442, R01-DK-044442, R01DK058379, R37DK058379, R01DK102487)
  • National Center for Research Resources (P20RR021940)
Topics
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords
bile acids, bile acid signaling, farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, G protein-coupled bile acid receptor, bile acid synthesis, diurnal cycle, gut microbiota, non-alcoholic fatty liver disease, inflammatory bowel disease, diabetes mellitus, obesity, drug metabolism, metabolic disorders, bile acid derivatives
MeSH terms
Animals, Bile Acids and Salts, Circadian Rhythm, Glucose, Humans, Liver, Metabolic Diseases, Models, Biological, Signal Transduction, MicroRNAs, Receptors, G-Protein-Coupled, Lipid Metabolism, Microbiota

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