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Cited by 580Drug Transport and Resistance MechanismsCholesterol and Lipid MetabolismLiver Disease Diagnosis and Treatment

Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy

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Chiang, John Y. L., Ferrell, Jessica M.·2020·American Journal of Physiology-Gastrointestinal and Liver Physiology
DOI 10.1152/ajpgi.00223.2019PMC PMC7099488
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Abstract

Bile acid synthesis is the most significant pathway for catabolism of cholesterol and for maintenance of whole body cholesterol homeostasis. Bile acids are physiological detergents that absorb, distribute, metabolize, and excrete nutrients, drugs, and xenobiotics. Bile acids also are signal molecules and metabolic integrators that activate nuclear farnesoid X receptor (FXR) and membrane Takeda G protein-coupled receptor 5 (TGR5; i.e., G protein-coupled bile acid receptor 1) to regulate glucose, lipid, and energy metabolism. The gut-to-liver axis plays a critical role in the transformation of primary bile acids to secondary bile acids, in the regulation of bile acid synthesis to maintain composition within the bile acid pool, and in the regulation of metabolic homeostasis to prevent hyperglycemia, dyslipidemia, obesity, and diabetes. High-fat and high-calorie diets, dysbiosis, alcohol, drugs, and disruption of sleep and circadian rhythms cause metabolic diseases, including alcoholic and nonalcoholic fatty liver diseases, obesity, diabetes, and cardiovascular disease. Bile acid-based drugs that target bile acid receptors are being developed for the treatment of metabolic diseases of the liver.

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  • Bile acids regulate liver growth via FXR and TGR5 receptors, which stimulate hepatocyte division and protect liver tissue from inflammatory damage.

    “Bile acids regulate liver growth via the farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5) receptors[70], which stimulate hepatocyte division and protect liver tissue from inflammatory damage.”

    From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [70]

    The Introduction describes anti-inflammatory effects of FXR and TGR5 signaling and says FXR helps prevent cholestatic liver injury. It does not establish that these receptors regulate liver growth or stimulate hepatocyte division; it also states that TGR5 is not expressed in hepatocytes. No page numbers are available in our copy. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Chiang, J. Y. L., & Ferrell, J. M.
Affiliations
Northeast Ohio Medical University (US)
Corresponding author
Chiang, John Y. L.
ORCID
Venue
American Journal of Physiology-Gastrointestinal and Liver Physiology
Publisher
American Physiological Society
Published
2020-03-01
Volume
318
Issue
3
Pages
G554-G573
ISSN
  • 0193-1857 (ISSN-L)
  • 1522-1547
DOI
10.1152/ajpgi.00223.2019
PMC
PMC7099488
OpenAlex
W3003103558
Cited by
580
References
29
Citations by year
2026: 191 · 2025: 115 · 2024: 88 · 2023: 67 · 2022: 68 · 2021: 33 · 2020: 18
FWCI
4.99
Type
journal article
Language
en
Open access
Locations
  • American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (44442, 58379)
Topics
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
Keywords
bile acid receptors, farnesoid X receptor, TGR5, hepatic steatosis, non-alcoholic fatty liver disease, alcoholic fatty liver, bile acid synthesis, cholesterol homeostasis, secondary bile acids, dysbiosis, metabolic homeostasis, metabolic disorders
MeSH terms
Receptor, Farnesoid X-Activated, Animals, Bile Acids and Salts, Fatty Liver, Gastrointestinal Agents, Humans, Liver, Signal Transduction, Receptors, Cytoplasmic and Nuclear, Receptors, G-Protein-Coupled

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