SREBP1 Contributes to Resolution of Pro-inflammatory TLR4 Signaling by Reprogramming Fatty Acid Metabolism
Open accessAbstract
Macrophages play pivotal roles in both the induction and resolution phases of inflammatory processes. Macrophages have been shown to synthesize anti-inflammatory fatty acids in an LXR-dependent manner, but whether the production of these species contributes to the resolution phase of inflammatory responses has not been established. Here, we identify a biphasic program of gene expression that drives production of anti-inflammatory fatty acids 12-24 hr following TLR4 activation and contributes to downregulation of mRNAs encoding pro-inflammatory mediators. Unexpectedly, rather than requiring LXRs, this late program of anti-inflammatory fatty acid biosynthesis is dependent on SREBP1 and results in the uncoupling of NFκB binding from gene activation. In contrast to previously identified roles of SREBP1 in promoting production of IL1β during the induction phase of inflammation, these studies provide evidence that SREBP1 also contributes to the resolution phase of TLR4-induced gene activation by reprogramming macrophage lipid metabolism.
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Upregulation of this lipid class is a common phenomenon in TLR4-mediated immune cell activation.
“upregulation of this lipid class is a common phenomenon in TLR4-mediated immune cell activation25.”
From Neurotoxic reactive astrocytes induce cell death via saturated lipids (2021) · cites this paper as [25]
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References 46 · Cited by 342
- Authors
- Oishi, Y., Spann, N. J., Link, V. M., Muse, E. D., Strid, T., Edillor, C., Kolar, M. J., Matsuzaka, T., Hayakawa, S., Tao, J., Kaikkonen, M. U., Carlin, A. F., Lam, M. T., Manabe, I., Shimano, H., Saghatelian, A., & Glass, C. K.
- Affiliations
- Tokyo Medical and Dental University (JP)
- University of California San Diego (US)
- Salk Institute for Biological Studies (US)
- University of Tsukuba (JP)
- University of Eastern Finland (FI)
- Chiba University (JP)
- Corresponding author
- Oishi, Yumiko
- Glass, Christopher K.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 25
- Issue
- 2
- Pages
- 412-427
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5568699
- OpenAlex
- W2566581841
- Cited by
- 342
- References
- 46
- Citations by year
- 2026: 29 · 2025: 40 · 2024: 31 · 2023: 43 · 2022: 45 · 2021: 49 · 2020: 40 · 2019: 23 · 2018: 27 · 2017: 15
- FWCI
- 22.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UEF eRepo (University of Eastern Finland) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- MEXT KAKENHI (24641142, 25H10)
- Naito Foundation
- Japan Heart Foundation
- Japan Foundation for Applied Enzymology
- Ono Medical Foundation
- Takeda Science Foundation
- Fondation Leducq Career Development Award
- Academy of Finland Research Fellowship
- Sigrid Jusélius
- ASLA-Fulbright
- Finnish Cultural Foundation
- Swedish Society for Medical Research
- NIH (DK091183, CA17390, HL088083, DK063491)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- SREBP1, TLR4 signaling, inflammation resolution, macrophages, fatty acid metabolism, anti-inflammatory fatty acids, NF-κB, lipid metabolism reprogramming, pro-inflammatory gene expression, IL-1β
- MeSH terms
- Liver X Receptors, Animals, Base Sequence, Enhancer Elements, Genetic, Fatty Acids, Inflammation, Lipopolysaccharides, Macrophages, Male, Mice, Inbred C57BL, Phenotype, Time Factors, Signal Transduction, Lipid Metabolism, Toll-Like Receptor 4, Sterol Regulatory Element Binding Protein 1, Biosynthetic Pathways
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