Autor(es): Salsinha, A. S. ; Socodato, R. ; Rodrigues, A. ; Vale-Silva, R. ; Relvas, J. B. ; Pintado, M. ; Rodríguez-Alcalá, L. M.
Data: 2023
Identificador Persistente: http://hdl.handle.net/10400.14/41171
Origem: Veritati - Repositório Institucional da Universidade Católica Portuguesa
Assunto(s): Microglia activation; Omega-3 fatty acids; Conjugated fatty acids; Obesity; Palmitic acid; Fructose
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.
