The benevolent bile: bile acids as stimulants of liver regeneration
Open accessAbstract
Bile acids are amphiphilic signaling molecules involved in a number of pathophysiological processes including digestion and adsorption of fats, inflammation, cell proliferation, and cancer.1–3 Whereas an increase in the intracellular levels of bile acid is generally associated with pathogenic outcomes, bile acids are critical for multiple nondigestive physiological processes at normal levels. One such process is liver regeneration, where bile acid plays a critical regulatory role.4–7 The liver is known for its remarkable capacity to regenerate after surgical resection or injury induced by viruses and chemicals.
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Elevated concentrations and a more hydrophilic BA pool promote liver regeneration after PHx.
“Growing evidence shows that elevated concentrations and a more hydrophilic BA pool promote liver regeneration after PHx.4,26,27”
From Constitutive Androstane Receptor Regulates Bile Acid Homeostasis and Metabolism During Liver Regeneration (2026) · cites this paper as [26]
In the main text (page not available), the paper says moderate bile-acid supplementation stimulates liver regeneration after partial hepatectomy. It does not say that a more hydrophilic bile-acid pool promotes regeneration, and it emphasizes physiological rather than generally elevated levels. (LLM, conf=0.86)
Experimental — accuracy not yet measuredHydrophobic BAs are cytotoxic but at tolerated concentrations can promote proliferation, whereas hydrophilic BAs, particularly UDCA and MCA, are cytoprotective.
“Hydrophobic BAs are cytotoxic but at tolerated concentrations can promote proliferation,26,27,31 whereas hydrophilic BAs, particularly ursodeoxycholic acid and MCA, are cytoprotective.32,33”
From Constitutive Androstane Receptor Regulates Bile Acid Homeostasis and Metabolism During Liver Regeneration (2026) · cites this paper as [26]
The opening section (page not provided) says increased intracellular bile-acid levels are generally associated with pathogenic outcomes, while bile acids at physiological levels stimulate liver regeneration. That supports the concentration-dependent contrast attributed to this source, but it does not identify hydrophobic bile acids specifically or establish that they are cytotoxic. The hydrophilic-bile-acid clause has separate citations and is not assessed against this source. (LLM, conf=0.84)
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Cites
Liver regeneration: biological and pathological mechanisms and implications
Michalopoulos, G. K., & Bhushan, B. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0342-4 · Cited by 998 · see citing works
Self-citationBile acids as regulatory molecules
Hylemon, P. B., Zhou, H., Pandak, W. M., Ren, S., Gil, G., & Dent, P. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r900007-jlr200 · Cited by 694 · see citing works
The receptor TGR5 protects the liver from bile acid overload during liver regeneration in mice
Péan, N., Doignon, I., Garcin, I., Besnard, A., Julien, B., Liu, B., Branchereau, S., Spraul, A., Guettier, C., Humbert, L., et al. (2013) · Hepatology · doi:10.1002/hep.26463 · Cited by 193 · see citing works
Promotion of liver regeneration/repair by farnesoid X receptor in both liver and intestine in mice
Zhang, L., Wang, Y.-D., Chen, W.-D., Wang, X., Lou, G., Liu, N., Lin, M., Forman, B. M., & Huang, W. (2012) · Hepatology · doi:10.1002/hep.25905 · Cited by 151 · see citing works
Bile Acid Flux Is Necessary for Normal Liver Regeneration
Naugler, W. E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097426 · Cited by 65 · see citing works
Flagged first, then by citations
Research works printed but not linked: 13
- [1]Li T. Apte U. Bile acid metabolism and signaling in cholestasis, inflammation, and cancer Adv Pharmacol 74 2015 263 302 26233910 PMC4615692
- [2]Zhou H. Hylemon P.B. Bile acids are nutrient signaling hormones Steroids 86 2014 62 68 24819989 PMC4073476
- [4]Alvarez-Sola G. Uriarte I. Latasa M.U. Jimenez M. Barcena-Varela M. Santamaria E. Urtasun R. Rodriguez-Ortigosa C. Prieto J. Berraondo P. Fernandez-Barrena M.G. Berasain C. Avila M.A. Bile acids, FGF15/19 and liver regeneration: from mechanisms to clinical applications Biochim Biophys Acta Mol Basis Dis 1864 2018 1326 1334 28709961
- [5]Merlen G. Ursic-Bedoya J. Jourdainne V. Kahale N. Glenisson M. Doignon I. Rainteau D. Tordjmann T. Bile acids and their receptors during liver regeneration: "dangerous protectors" Mol Aspects Med 56 2017 25 33 28302491
- [6]Bhushan B. Apte U. Liver regeneration after acetaminophen hepatotoxicity: mechanisms and therapeutic opportunities Am J Pathol 189 2019 719 729 30653954 PMC6446224
- [7]Bhushan B. Borude P. Edwards G. Walesky C. Cleveland J. Li F. Ma X. Apte U. Role of bile acids in liver injury and regeneration following acetaminophen overdose Am J Pathol 183 2013 1518 1526 24007882 PMC3814573
- [9]Chiang J.Y. Bile acids: regulation of synthesis J Lipid Res 50 2009 1955 1966 19346330 PMC2739756
- [11]Huang W. Ma K. Zhang J. Qatanani M. Cuvillier J. Liu J. Dong B. Huang X. Moore D.D. Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration Science 312 2006 233 236 16614213
- [13]Borude P. Edwards G. Walesky C. Li F. Ma X. Kong B. Guo G.L. Apte U. Hepatocyte-specific deletion of farnesoid X receptor delays but does not inhibit liver regeneration after partial hepatectomy in mice Hepatology 56 2012 2344 2352 22730081 PMC3469721
- [15]Kong B. Huang J. Zhu Y. Li G. Williams J. Shen S. Aleksunes L.M. Richardson J.R. Apte U. Rudnick D.A. Guo G.L. Fibroblast growth factor 15 deficiency impairs liver regeneration in mice Am J Physiol Gastrointest Liver Physiol 306 2014 G893 G902 24699334 PMC4024724
- [16]Wang Y. Li J. Matye D. Zhang Y. Dennis K. Ding W.X. Li T. Bile acids regulate cysteine catabolism and glutathione regeneration to modulate hepatic sensitivity to oxidative injury JCI Insight 3 2018 PMC5931126 29669937
- [17]Huang M. Williams J. Kong B. Zhu Y. Li G. Zhu Z. Guo G.L. Fibroblast growth factor 15 deficiency increases susceptibility but does not improve repair to acetaminophen-induced liver injury in mice Dig Liver Dis 50 2018 175 180 28867475
- [18]Alvarez-Sola G. Uriarte I. Latasa M.U. Jimenez M. Barcena-Varela M. Santamaria E. Urtasun R. Rodriguez-Ortigosa C. Prieto J. Corrales F.J. Baulies A. García-Ruiz C. Fernandez-Checa J.C. Berraondo P. Fernandez-Barrena M.G. Berasain C. Avila M.A. Engineered fibroblast growth factor 19 protects from acetaminophen-induced liver injury and stimulates aged liver regeneration in mice Cell Death Dis 8 2017 e3083 PMC5682649 28981086
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Sorted by citations
Zhou, W., Chembazhi, U. V., Huang, J., Bangru, S., Dean, A. E., Asokakumar, A., Kalsotra, A., Rudnick, D. A., & Anakk, S. (2026) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2026.101858
- Authors
- Bhushan, B., & Apte, U.
- Affiliations
- University of Pittsburgh (US)
- University of Kansas Medical Center (US)
- Corresponding author
- Apte, Udayan
- Venue
- Cellular and Molecular Gastroenterology and Hepatology
- Publisher
- Elsevier BV
- Published
- 2022
- Volume
- 13
- Issue
- 5
- Pages
- 1478-1480
- ISSN
- 2352-345X (ISSN-L)
- PMC
- PMC9043297
- OpenAlex
- W4213289545
- Cited by
- 4
- References
- 5
- Citations by year
- 2026: 2 · 2024: 1 · 2022: 1
- FWCI
- 0.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cellular and Molecular Gastroenterology and Hepatology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (R01 DK98414)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- bile acids, liver regeneration, bile acid signaling, hepatocyte proliferation, liver injury, surgical resection, hepatoprotection
- MeSH terms
- Bile, Bile Acids and Salts, Hepatectomy, Humans, Hyperplasia, Liver, Liver Regeneration
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