The Crosstalk between Hepatocytes, Hepatic Macrophages, and Hepatic Stellate Cells Facilitates Alcoholic Liver Disease
Open accessAbstract
Choi et al. (2019) explored the pathogenesis of alcohol-induced de novo lipogenesis in mice with ALD to reveal a novel mechanism of cannabinoid 1 receptor (CB1R)-SREB1-dependent triglyceride synthesis that requires crosstalk between hepatocytes and HSCs. Using genetic and pharmacological inhibition of the key components of the xCT-glutamate→mGluR5-2-AG→CB 1 R-SREBP1-FASN paracrine communication system, Choi et al. identified potential new targets for drugs for ALD.
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LPS-mediated activation of KCs via TLR4 leading to MyD88-dependent activation of NF-kB, production of proinflammatory cytokines and subsequent liver injury has been demonstrated for both MASH and ASH.
“LPS-mediated activation of KCs via TLR4 leading to MyD88-dependent activation of NF-kB, production of proinflammatory cytokines and subsequent liver injury have also been demonstrated for both MASH(214) and ASH(215).”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [215]
The available passage contains only a corrupted title and the Acknowledgments and References headings; it has no substantive text or page number. Searches for LPS/TLR4, MyD88, Kupffer cells, and alcoholic steatohepatitis returned no additional passage, so our copy cannot verify the ASH mechanism attributed to this paper. (LLM, conf=0.76)
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Cites
ER Stress Drives Lipogenesis and Steatohepatitis via Caspase-2 Activation of S1P
Kim, J. Y., Garcia-Carbonell, R., Yamachika, S., Zhao, P., Dhar, D., Loomba, R., Kaufman, R. J., Saltiel, A. R., & Karin, M. (2018) · Cell · doi:10.1016/j.cell.2018.08.020 · Cited by 333 · see citing works
Multigenerational epigenetic adaptation of the hepatic wound-healing response
Zeybel, M., Hardy, T., Wong, Y. K., Mathers, J. C., Fox, C. R., Gackowska, A., Oakley, F., Burt, A. D., Wilson, C. L., Anstee, Q. M., et al. (2012) · Nature Medicine · doi:10.1038/nm.2893 · Cited by 279 · see citing works
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Bi, Y., Guo, X., Zhang, M., Zhu, K., Shi, C., Fan, B., Wu, Y., Yang, Z., & Ji, G. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-021-02663-5 · Cited by 82 · see citing works
The liver as a central "hub" of the immune system: pathophysiological implications
Ronca, V., Gerussi, A., Collins, P., Parente, A., Oo, Y. H., & Invernizzi, P. (2025) · Physiological Reviews · doi:10.1152/physrev.00004.2023 · Cited by 59 · see citing works
- Authors
- Kisseleva, T., & Brenner, D. A.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Kisseleva, Tatiana
- Brenner, David A.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2019-11
- Volume
- 30
- Issue
- 5
- Pages
- 850-852
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2983390962
- Cited by
- 39
- References
- 2
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 6 · 2023: 7 · 2022: 4 · 2021: 8 · 2020: 2
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Foundation for the National Institutes of Health
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- alcoholic liver disease, hepatocytes, hepatic stellate cells, hepatic macrophages, de novo lipogenesis, triglyceride synthesis, cannabinoid 1 receptor, SREBP1, fatty acid synthase, mGluR5, 2-arachidonoylglycerol, paracrine signaling, therapeutic target
- MeSH terms
- Animals, Glutamates, Liver Diseases, Alcoholic, Macrophages, Hepatocytes, Mice, Hepatic Stellate Cells
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