The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
UCP2-induced fatty acid synthase promotes NLRP3 inflammasome activation during sepsis
Open accessAbstract
Cellular lipid metabolism has been linked to immune responses; however, the precise mechanisms by which de novo fatty acid synthesis can regulate inflammatory responses remain unclear. The NLRP3 inflammasome serves as a platform for caspase-1-dependent maturation and secretion of proinflammatory cytokines. Here, we demonstrated that the mitochondrial uncoupling protein-2 (UCP2) regulates NLRP3-mediated caspase-1 activation through the stimulation of lipid synthesis in macrophages. UCP2-deficient mice displayed improved survival in a mouse model of polymicrobial sepsis. Moreover, UCP2 expression was increased in human sepsis. Consistently, UCP2-deficient mice displayed impaired lipid synthesis and decreased production of IL-1β and IL-18 in response to LPS challenge. In macrophages, UCP2 deficiency suppressed NLRP3-mediated caspase-1 activation and NLRP3 expression associated with inhibition of lipid synthesis. In UCP2-deficient macrophages, inhibition of lipid synthesis resulted from the downregulation of fatty acid synthase (FASN), a key regulator of fatty acid synthesis. FASN inhibition by shRNA and treatment with the chemical inhibitors C75 and cerulenin suppressed NLRP3-mediated caspase-1 activation and inhibited NLRP3 and pro-IL-1β gene expression in macrophages. In conclusion, our results suggest that UCP2 regulates the NLRP3 inflammasome by inducing the lipid synthesis pathway in macrophages. These results identify UCP2 as a potential therapeutic target in inflammatory diseases such as sepsis.
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“the uncoupling protein 2, a driver for fatty acid synthesis, activates NLRP3 inflammasome [70].”
From HIV-TAT dysregulates microglial lipid metabolism through SREBP2/miR-124 axis: Implication of lipid droplet accumulation microglia in NeuroHIV (2025) · cites this paper as [70]
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Cites
Chen, Y., Wang, L., Kang, Q., Zhang, X., Yu, G., Wan, X., Wang, J., & Zhu, K. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000477308 · Cited by 10,730
Intensive insulin therapy in critically ill patients.
Van den Berghe, G., Wouters, P., Weekers, F., Verwaest, C., Bruyninckx, F., Schetz, M., Vlasselaers, D., Ferdinande, P., Lauwers, P., & Bouillon, R. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa011300 · Cited by 9,977
Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock
Dellinger, R. P., Levy, M. M., Rhodes, A., Annane, D., Gerlach, H., Opal, S. M., Sevransky, J. E., Sprung, C. L., Douglas, I. S., Jaeschke, R., et al. (2013) · Critical Care Medicine · doi:10.1097/ccm.0b013e31827e83af · Cited by 9,694
Dellinger, R. P., Levy, M. M., Rhodes, A., Annane, D., Gerlach, H., Opal, S. M., Sevransky, J., Sprung, C. L., Douglas, I. S., Jaeschke, R., et al. (2013) · Intensive Care Medicine · doi:10.1007/s00134-012-2769-8 · Cited by 7,371
Intravenous Fluids and Acute Kidney Injury
Ding, X., Cheng, Z., & Qian, Q. (2017) · Blood Purification · doi:10.1159/000452702 · Cited by 6,868
2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference
Levy, M. M., Fink, M. P., Marshall, J. C., Abraham, E. H., Angus, D. C., Cook, D., Cohen, J., Opal, S. M., Vincent, J., & Ramsay, G. (2003) · Critical Care Medicine · doi:10.1097/01.ccm.0000050454.01978.3b · Cited by 5,976
Schroder, K., & Tschopp, J. (2010) · Cell · doi:10.1016/j.cell.2010.01.040 · Cited by 5,475
The Pathophysiology and Treatment of Sepsis
Hotchkiss, R. S., & Karl, I. E. (2003) · New England Journal of Medicine · doi:10.1056/nejmra021333 · Cited by 4,134
Severe Sepsis and Septic Shock
Angus, D. C., & van der Poll, T. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1208623 · Cited by 4,119
The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation
DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G., & Thompson, C. B. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.002 · Cited by 4,088
Research works printed but not linked: 2
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Metadata
- Authors
- Moon, J.-S., Lee, S., Park, M.-A., Siempos, I. I., Haslip, M., Lee, P. J., Yun, M., Kim, C. K., Howrylak, J., Ryter, S. W., Nakahira, K., & Choi, A. M. K.
- Affiliations
- NewYork–Presbyterian Hospital (US)
- Brigham and Women's Hospital (US)
- Yale University (US)
- Pennsylvania State University (US)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2015-01-09
- Volume
- 125
- Issue
- 2
- Pages
- 665-680
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC4319445
- OpenAlex
- W2064173000
- Cited by
- 238
- References
- 70
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 16 · 2023: 23 · 2022: 26 · 2021: 33 · 2020: 32 · 2019: 24 · 2018: 24 · 2017: 28 · 2016: 15 · 2015: 9
- FWCI
- 11.01
- Type
- journal article
- Language
- en
- Status
- Retracted
- Update notices
- retraction (2023-03-15)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Strong
- European Society of Intensive Care Medicine
- National Institutes of Health
- College of Veterinary Medicine, Cornell University
- Weill Cornell Medical College
- National Heart, Lung, and Blood Institute (R01HL055330, R01HL079904, P01HL108801, R01HL060234, R01HL112747, P01HL114501)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- UCP2, fatty acid synthase, NLRP3 inflammasome, sepsis, macrophages, lipid metabolism, caspase-1 activation, IL-1β, IL-18, lipopolysaccharide, mitochondrial uncoupling, cerulenin, C75, therapeutic target
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Uncoupling Protein 2, Animals, Carrier Proteins, Enzyme Induction, Humans, Ion Channels, Lipids, Macrophages, Down-Regulation, Mice, Knockout, Sepsis, Caspase 1, Interleukin-18, Mitochondrial Proteins, Mice, Interleukin-1beta, Fatty Acid Synthase, Type I, Inflammasomes
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