The emerging role of metabolic regulation in the functioning of Toll‐like receptors and the NOD‐like receptor Nlrp3
Open accessAbstract
While it has long been suspected that inflammation participates in the pathogenesis of metabolic disorders such as the insulin resistance that occurs in type 2 diabetes, recent work suggests that this is not the only important interaction between metabolism and inflammation. Inroads into the understanding of the relationship between metabolic pathways and inflammation are indicating that signaling by innate immune receptors such as TLR4 and Nlrp3 regulate metabolism. TLRs have been shown to promote glycolysis, whilst Nlrp3‐mediated production of IL‐1β causes insulin resistance. A key role for the hypoxia‐sensing transcription factor HIF1α in the functioning of macrophages activated by TLRs has also recently emerged. This review will assess recent evidence for these complex interactions and speculate on their importance for innate immunity and inflammation.
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Ligation of TLR4 by LPS can transcriptionally induce HIF-1α and a range of HIF-1α target genes under hypoxic and normoxic conditions in an NF-κB-dependent manner.
“Ligation of TLR4 by LPS can transcriptionally induce HIF-1α and the induction of a range of HIF-1α target genes under hypoxic and also normoxic conditions2, in an NF-κB-dependent manner19.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [19]
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- Authors
- Tannahill, G. M., & O'Neill, L. A. J.
- Affiliations
- Trinity College Dublin (IE)
- Corresponding author
- Tannahill, Gillian M.
- ORCID
- O'Neill, Luke A.J.
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2011-05-06
- Volume
- 585
- Issue
- 11
- Pages
- 1568-1572
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2013404857
- Cited by
- 84
- References
- 55
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 3 · 2021: 6 · 2020: 8 · 2019: 5 · 2018: 6 · 2017: 1 · 2016: 5 · 2015: 3 · 2014: 5 · 2013: 12 · 2012: 11
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- FEBS Letters (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- Toll-like receptors, metabolic regulation, inflammation, insulin resistance, type 2 diabetes, glycolysis, IL-1β, HIF-1α, hypoxia, macrophages, innate immunity
- MeSH terms
- Animals, Carrier Proteins, Dendritic Cells, Glycolysis, Humans, Macrophages, Myeloid Cells, Toll-Like Receptors
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