Pintado, Manuela E.

Relvas, João B.

Rodrigues, Artur

Rodríguez-Alcalá, Luis Miguel

Salsinha, Ana Sofia

Socodato, Renato

English

Repositório Institucional da Universidade Católica Portuguesa

CLA and CLNA ameliorate neuroinflammation and cellular oxidation related with western dietsAna Sofia Salsinhaa,b, Renato Socodatob, Artur Rodriguesb, Luis Miguel Rodríguez-Alcaláa*, João B. Relvasb, Manuela E. Pintadoa*.a. Universidade Católica Portuguesa, CBQF - Centro de Biotecnologia e Química Fina –Laboratório Associado, Escola Superior deBiotecnologia, Rua de Diogo Botelho, 1327, 4169-005 Porto, Portugalb. Instituto de Investigação e Inovação em Saúde and Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto – RuaAlfredo Allen, 208, 4200-135 Porto, Portugal*corresponding authors: Rodríguez-Alcalá LM: lalcala@ucp.pt, Pintado ME: mpintado@ucp.ptBy using chemical agonists and antagonists of GPR120/FFA4 it was demonstrated that while omega-3, CLA and CLNA effect on NFkB pathway inhibition is mediated by this receptor, the antioxidant ability of omega-3 and CLA occurs through different signaling mechanisms. It was suggested, for the first time, that CLA and CLNA have a similar action to omega-3 on microglia, probably via GPR120 activation and modulation of NFkB-associated inflammatory pathways. Introduction and objectivesExperimental design and ResultsAcknowledgementsHigh-fat diet has been associated with a chronic-low grade inflammation in both adipose tissue and central nervous system. Moreover, fatty acids (FAs) are known tocross the blood-brain barrier and reach the central nervous system. Microglia express a wide range of lipid-sensitive receptors, potentially triggering inflammatoryresponses. Therefore, FAs can exert both pro (e.g. saturated fatty acids, SFAs) and anti-inflammatory (e.g. polyunsaturated fatty acids, PUFAs) effects in thehypothalamus. Although the mechanisms of action have not been fully described yet, GPR120/FFA4 receptor activation by omega-3 FA results into the inhibition of theNFkB pathway. Considering the beneficial role of conjugated linoleic acid (CLA) and conjugated linolenic acid isomers (CLNA) in obesity, namely their anti-inflammatoryproperties, we hypothesized that they may present similar properties as omega-3 fatty acids in hypothalamus. Thus, in this work through live cell imaging and FRETtechnology, and using a human microglia cell model (HMC3), we assessed the modulatory potential of a solution mimicking the western pattern diet (palmitic acid, a SFA,and fructose) and the preventive role of different PUFAs (Omega-3 – EPA and DHA-, CLA and CLNA isomers), specifically targeting the NFkB pathway and oxidative stressthrough reactive oxygen species (ROS) production. By using chemical agonists (TUG-891) and antagonists (AH-7614) of GPR120/FFA4 we determined if Omega-3, CLAand CLNA modulatory effects are mediated by this receptor.Author Ana Sofia Salsinha would like to thank FCT for her PhD grant (SFRH/BD/136857/2018). The authors would also like to thank the scientific collaboration under the FCT projectUID/Multi/50016/2020. Furthermore, the authors acknowledge the support of i3S Scientific Platform Advanced Light Microscopy, member of the national infrastructure PPBI-PortuguesePlatform of BioImaging (supported by POCI-01-0145-FEDER-022122).Two-way ANOVA in relation to Frut+PA, where no pre-incubation with the selected fatty acids was performed: *p<0.05, **p<0.01,***p<0.001, ****p<0.0001 and in relation to cells which were pre-incubated with omega 3/CLA/CLNA and AH7614, a GPR120/FFA4inhibitor: #p<0.05, ##p<0.01, ###p<0.001, ####p<0.0001.Two-way ANOVA in relation toFrut+PA, where no pre-incubationwith the selected fatty acids wasperformed. *p<0.05, **p<0.01,***p<0.001, ****p<0.0001.Omega-3, CLA and CLNA fatty acids inhibit Fructose+Palmitic acid (Frut+PA)induced-NFkB pathway activation through GPR120/FFA4 receptor activation.It was suggested, for the first time, that CLA and CLNA have a similar actionto omega-3 on microglia. Omega-3 and CLA present antioxidant capacity byinhibiting Fructose+Palmitic acid (Frut+PA) induced-ROS production, butsuch effect is not mediated by GPR120/FFA4 (results not shown).

CLA and CLNA ameliorate neuroinflammation and cellular oxidation related with western diets

https://repositorio.ucp.pt/bitstream/10400.14/36781/1/10713_29260_HENU_019.pdf

CLA and CLNA ameliorate neuroinflammation and cellular oxidation related with western diets

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