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Bile acids as regulatory molecules
Open accessAbstract
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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In the citing paper
“This process is controlled by a negative-feedback loop through the activation of the nuclear farnesoid X receptor (FXR) in the ileum and liver (7, 8).”
In the citing paper
“BAs are synthesized from cholesterol by CYP7A1 in the liver and play a central role in cholesterol homoeostasis (8).”
In the citing paper
“Bile acids are cholesterol metabolites that facilitate the absorption of dietary fat and fat-soluble molecules and are now also recognized as regulators of energy metabolism through activation of the receptors TGR5 and FXR (Hylemon et al., 2009; Lefebvre et al., 2009).”
From Roux-en-Y Gastric Bypass and Vertical Banded Gastroplasty Induce Long-Term Changes on the Human Gut Microbiome Contributing to Fat Mass Regulation (2015) · cites this paper as Hylemon et al., 2009
In the citing paper
“Following systemic adsorption, some secondary BAs in turn impact host physiology though interaction with a variety of host nuclear receptors including FXR, liver X receptor (LXR), pregnane X receptor (PXR), and specific G-protein coupled receptors like TGR5 (Figure 1)40–44.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [40]
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Metadata
- 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.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 50
- Issue
- 8
- Pages
- 1509-1520
- ISSN
- 0022-2275 (ISSN-L)
- 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
- 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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