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Potential of omega-3 and conjugated fatty acids to control microglia inflammatory imbalance elicited by obesogenic nutrients

Authors :
Salsinha, A. S.
Socodato, R.
Rodrigues, A.
Vale-Silva, R.
Relvas, J. B.
Pintado, M.
Rodríguez-Alcalá, L. M.
Veritati - Repositório Institucional da Universidade Católica Portuguesa
Source :
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1868:159331
Publication Year :
2023
Publisher :
Elsevier BV, 2023.

Abstract

High-fat diet-induced obesity detrimentally affects brain function by inducing chronic low-grade inflammation. This neuroinflammation is, at least in part, likely to be mediated by microglia, which are the main immune cell population in the brain. Microglia express a wide range of lipid-sensitive receptors and their activity can be modulated by fatty acids that cross the blood-brain barrier. Here, by combining live cell imaging and FRET technology we assessed how different fatty acids modulate microglia activity. We demonstrate that the combined action of fructose and palmitic acid induce Ikβα degradation and nuclear translocation of the p65 subunit nuclear factor kB (NF-κB) in HCM3 human microglia. Such obesogenic nutrients also lead to reactive oxygen species production and LynSrc activation (critical regulators of microglia inflammation). Importantly, short-time exposure to omega-3 (EPA and DHA), CLA and CLNA are sufficient to abolish NF-κB pathway activation, suggesting a potential neuroprotective role. Omega-3 and CLA also show an antioxidant potential by inhibiting reactive oxygen species production, and the activation of LynSrc in microglia. Furthermore, using chemical agonists (TUG-891) and antagonists (AH7614) of GPR120/FFA4, we demonstrated that omega-3, CLA and CLNA inhibition of the NF-κB pathway is mediated by this receptor, while omega-3 and CLA antioxidant potential occurs through different signaling mechanisms.

Details

ISSN :
13881981
Volume :
1868
Database :
OpenAIRE
Journal :
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
Accession number :
edsair.doi.dedup.....f6d38e349f43d631b3639444eb23994d
Full Text :
https://doi.org/10.1016/j.bbalip.2023.159331