Bile Acid Receptors and the Gut–Liver Axis in Nonalcoholic Fatty Liver Disease
Open accessAbstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) has been significantly increased due to the global epidemic of obesity. The disease progression from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH) is closely linked to inflammation, insulin resistance, and dysbiosis. Although extensive efforts have been aimed at elucidating the pathological mechanisms of NAFLD disease progression, current understanding remains incomplete, and no effective therapy is available. Bile acids (BAs) are not only important physiological detergents for the absorption of lipid-soluble nutrients in the intestine but also metabolic regulators. During the last two decades, BAs have been identified as important signaling molecules involved in lipid, glucose, and energy metabolism. Dysregulation of BA homeostasis has been associated with NAFLD disease severity. Identification of nuclear receptors and G-protein-coupled receptors activated by different BAs not only significantly expanded the current understanding of NAFLD/NASH disease progression but also provided the opportunity to develop potential therapeutics for NAFLD/NASH. In this review, we will summarize the recent studies with a focus on BA-mediated signaling pathways in NAFLD/NASH. Furthermore, the therapeutic implications of targeting BA-mediated signaling pathways for NAFLD will also be discussed.
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Dysbiosis of bile acids has been associated with MAFLD and increased synthesis of primary bile acids has been observed in patients with NASH.
“Dysbiosis of bile acids has been associated with MAFLD and increased synthesis of pBAs has been observed in patients with NASH (Xue et al., 2021).”
From <i>Akkermansia muciniphila</i> alleviates <scp>high‐fat‐diet</scp> ‐related metabolic‐associated fatty liver disease by modulating gut microbiota and bile acids (2023) · cites this paper as Xue et al., 2021
The Introduction (§1; page unavailable) links disrupted bile-acid homeostasis with progression of NAFLD, and §4 reports increased circulating conjugated primary bile acids in patients with NASH. The paper discusses NAFLD rather than explicitly using MAFLD for this association, and increased circulating levels do not establish the claimed increase in primary bile-acid synthesis. (LLM, conf=0.86)
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- Authors
- Xue, R., Su, L., Lai, S., Wang, Y., Zhao, D., Fan, J., Chen, W., Hylemon, P. B., & Zhou, H.
- Affiliations
- Department of Gastroenterology, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 210092, China
- Virginia Commonwealth University (US)
- Anhui University of Traditional Chinese Medicine (CN)
- Corresponding author
- Zhou, Huiping
- Venue
- Cells
- Publisher
- MDPI AG
- Published
- 2021-10-20
- Volume
- 10
- Issue
- 11
- Pages
- 2806
- ISSN
- 2073-4409 (ISSN-L)
- PMC
- PMC8616422
- OpenAlex
- W3205794985
- Cited by
- 95
- References
- 110
- Citations by year
- 2026: 17 · 2025: 22 · 2024: 19 · 2023: 24 · 2022: 13
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cells (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (R01 DK104893 and R01DK-057543 to HZ and PBH, 1 R21 AA026629-01 to HZ)
- United States Department of Veterans Affairs (I01BX004033 to HZ and 1BX001328 to PBH); Research Career Scientist Award (IK6BX004477 to HZ); ShEEP grant (1 IS1 BX004777-01 to HZ);)
- National Natural Science Foundation of China (No. 81873565)
- National Key R&D Program of China (No.2017YFC0908903)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- bile acid receptors, gut-liver axis, non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, bile acids, nuclear receptors, G protein-coupled receptors, dysbiosis, insulin resistance, obesity
- MeSH terms
- Animals, Bile Acids and Salts, Humans, Liver, Receptors, Cell Surface, Signal Transduction, Gastrointestinal Tract, Non-alcoholic Fatty Liver Disease
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