Cited by 697Drug Transport and Resistance MechanismsCholesterol and Lipid MetabolismLipid metabolism and disorders

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Bile acids as regulatory molecules

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Hylemon, Phillip B., Zhou, Huiping, Pandak, William M., Ren, Shunlin, Gil, Gregorio, Dent, Paul·2009·Journal of Lipid Research

DOI 10.1194/jlr.r900007-jlr200PMC PMC2724047

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Abstract

In the past, bile acids were considered to be just detergent molecules derived from cholesterol in the liver. They were known to be important for the solubilization of cholesterol in the gallbladder and for stimulating the absorption of cholesterol, fat-soluble vitamins, and lipids from the intestines. However, during the last two decades, it has been discovered that bile acids are regulatory molecules. Bile acids have been discovered to activate specific nuclear receptors (farnesoid X receptor, preganane X receptor, and vitamin D receptor), G protein coupled receptor TGR5 (TGR5), and cell signaling pathways (c-jun N-terminal kinase 1/2, AKT, and ERK 1/2) in cells in the liver and gastrointestinal tract. Activation of nuclear receptors and cell signaling pathways alter the expression of numerous genes encoding enzyme/proteins involved in the regulation of bile acid, glucose, fatty acid, lipoprotein synthesis, metabolism, transport, and energy metabolism. They also play a role in the regulation of serum triglyceride levels in humans and rodents. Bile acids appear to function as nutrient signaling molecules primarily during the feed/fast cycle as there is a flux of these molecules returning from the intestines to the liver following a meal. In this review, we will summarize the current knowledge of how bile acids regulate hepatic lipid and glucose metabolism through the activation of specific nuclear receptors and cell signaling pathways.

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Authors: Hylemon, P. B., Zhou, H., Pandak, W. M., Ren, S., Gil, G., & Dent, P.
Affiliations: Virginia Commonwealth University (US)
Corresponding author: Hylemon, Phillip B.
ORCID: Hylemon, Phillip B.
Zhou, Huiping
Pandak, William M.
Ren, Shunlin
Gil, Gregorio
Dent, Paul
Venue: Journal of Lipid Research
Publisher: Elsevier BV
Published: 2009-08
Volume: 50
Issue: 8
Pages: 1509-1520
ISSN: 0022-2275 (ISSN-L)
DOI: 10.1194/jlr.r900007-jlr200
PMC: PMC2724047
OpenAlex: W2165877587
Cited by: 694
References: 99
Citations by year: 2026: 25 · 2025: 29 · 2024: 37 · 2023: 40 · 2022: 43 · 2021: 51 · 2020: 37 · 2019: 52 · 2018: 36 · 2017: 43 · 2016: 43 · 2015: 50 · 2014: 50 · 2013: 46 · 2012: 39
FWCI: 3.30
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 4039 d)
Locations: Journal of Lipid Research (publishedVersion, cc-by)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK52825, R01DK052825, DK-057543, R01DK057543)
Topics: Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords: bile acids, bile acid signaling, farnesoid X receptor, pregnane X receptor, vitamin D receptor, TGR5, c-Jun N-terminal kinase, Akt signaling, ERK signaling, hepatic lipid metabolism, hepatic glucose metabolism, nutrient sensing, serum triglycerides, bile acid transport, energy metabolism
MeSH terms: Animals, Bile, Bile Acids and Salts, Digestion, Enterohepatic Circulation, Fibroblast Growth Factors, Humans, Liver, Signal Transduction, Receptors, Cytoplasmic and Nuclear, Gastrointestinal Tract, Receptors, G-Protein-Coupled

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