The relationship between omega-3 sources and the GPR120 receptor in different inflammatory states

Author(s)

Susana Castelo Branco Ramos Nakandakari

• Document type: Doctoral Thesis
• Press: Limeira, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas
• Defense date: 2023-11-01

Examining board members

Dennys Esper Cintra; Maria Cláudia Gonçalves de Oliveira; Eli Mansur; Helen Hermana Miranda Hermsdorff; André Gustavo Vasconcelos Costa

• Advisor: Dennys Esper Cintra; José Rodrigo Pauli

Abstract

Omega 3 fatty acids ('omega'3) are target of current studies due to their anti-inflammatory effects, once the cellular signaling coordinated by GPR120 receptor appears to be one of the most relevant. When activated by 'omega'3, the GPR120 attenuates the inflammatory process by inhibiting NFkB, through the TAB1 protein, decreasing the inflammation. The presence of GPR120 was shown in central and peripheral tissues, but also in cells of the immune system, such as Kupffer cells and macrophages. Investigations on 'omega'3 supplementation in infectious diseases such as sepsis has evolved, but there is still no consensus on whether its use improves patient survival. The aim of this study is to evaluate the behavior of the GPR120 receptor in different inflammatory conditions and to establish the possible mechanisms associated with these changes. For in vivo experiments, C57BL/6J mice subjected to low or high-grade inflammation, through the protocols of high-fat diet (HF) intake, cecal ligation and puncture (CLP) or administration of lipopolysaccharides (LPS). For in vitro experiments, 3T3-L1 and RAW 264.7 cell lines, adipocytes and macrophages, respectively, were used, in addition to the primary culture of bone marrow-derived macrophages (BMDM), adipocytes and stromal vascular fraction (SVF). The response pattern of cytokines and the GPR120 receptor (Ffar4) in epididymal adipose tissue and cells were analyzed using RT-qPCR. In both in vivo and in vitro protocols, when stimulated with LPS, Ffar4 was reduced in relation to its control, while in vivo protocols under HF, Ffar4 did not change and in macrophages treated with palmitate, Ffar4 increased. Furthermore, sources of 'omega'3, flaxseed oil (FS) and fish oil (FO) were offered via gavage to mice prior to the development of sepsis and parameters such as survival were evaluated. The FO group had a lower survival rate compared to the other groups. Our findings suggest that GPR120 is not only a nutritional receptor, but also has a role in the inflammatory response. However, when 'omega'3 supplementation was used in sepsis, the groups with 'omega'3 sources were not able to improve the survival rate (AU)

• FAPESP's process: 19/13168-3 - The influence of GPR120 in the immune system
• Grantee: Susana Castelo Branco Ramos Nakandakari
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)