STING orchestrates the crosstalk between polyunsaturated fatty acid metabolism and inflammatory responses.
FADS2
STING
cGAS
cytosolic DNA
delta-6 Desaturase
inflammation
interferon responses
metabolism
nucleic acid immunity
polyunsaturated fatty acids
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
04 01 2022
04 01 2022
Historique:
received:
28
01
2021
revised:
28
09
2021
accepted:
06
12
2021
entrez:
5
1
2022
pubmed:
6
1
2022
medline:
8
4
2022
Statut:
ppublish
Résumé
Concerted alteration of immune and metabolic homeostasis underlies several inflammation-related pathologies, ranging from metabolic syndrome to infectious diseases. Here, we explored the coordination of nucleic acid-dependent inflammatory responses and metabolic homeostasis. We reveal that the STING (stimulator of interferon genes) protein regulates metabolic homeostasis through inhibition of the fatty acid desaturase 2 (FADS2) rate-limiting enzyme in polyunsaturated fatty acid (PUFA) desaturation. STING ablation and agonist-mediated degradation increased FADS2-associated desaturase activity and led to accumulation of PUFA derivatives that drive thermogenesis. STING agonists directly activated FADS2-dependent desaturation, promoting metabolic alterations. PUFAs in turn inhibited STING, thereby regulating antiviral responses and contributing to resolving STING-associated inflammation. Thus, we have unveiled a negative regulatory feedback loop between STING and FADS2 that fine-tunes inflammatory responses. Our results highlight the role of metabolic alterations in human pathologies associated with aberrant STING activation and STING-targeting therapies.
Identifiants
pubmed: 34986331
pii: S1550-4131(21)00626-4
doi: 10.1016/j.cmet.2021.12.007
pmc: PMC8733004
pii:
doi:
Substances chimiques
Fatty Acids, Unsaturated
0
Fatty Acid Desaturases
EC 1.14.19.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
125-139.e8Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests J.M. is a joint PhD student in Azelead, a startup company, and the Laguette laboratory. All other authors declare no competing interests.
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