Omega-3 mechanism of action in inflammation and endoplasmic reticulum stress in mononuclear cells from overweight non-alcoholic fatty liver disease participants: study protocol for the ``Brazilian Omega Study{''} (BROS)-a randomized controlled trial

Author(s):Show less -

Batista, Ellencristina Silva ^{[1, 2, 3, 4]} ; da Silva Rios, Thaiane ^{[2, 4]} ; Munoz, Vitor Rosetto ^{[5, 4]} ; Jesus, Joyce Santos ^[3] ; Vasconcelos, Marcel Monteiro ^[3] ; da Cunha, Diogo Thimoteo ^[6] ; Marques-Rocha, Jose Luis ^[7] ; Nakandakari, Susana Castelo Branco Ramos ^{[2, 4]} ; Lara, Roberta ^[2] ; da Silva, Adelino Sanchez Ramos ^[8] ; Pauli, Jose Rodrigo ^{[5, 4]} ; Ropelle, Eduardo Rochete ^{[5, 4]} ; Mekary, Rania Angelina ^{[9, 10]} ; de Moura, Leandro Pereira ^[5] ; Camargo, Enilton Aparecido ^[11] ; Cintra, Dennys Esper ^{[2, 4]}

Affiliation:Show less -

^[1] Univ Fed Sergipe, Graduate Program Hlth Sci PPGCS, Aracaju, Sergipe - Brazil

^[2] Univ Estadual Campinas, Sch Appl Sci, Lab Nutr Genom, 1300 Zip, BR-13484350 Pedro Zaccaria, Limeira - Brazil

^[3] Univ Fed Sergipe, Nutr Dept, Lagarto, Sergipe - Brazil

^[4] Univ Estadual Campinas, Sch Appl Sci, Lipids & Nutrigen Res Ctr, Limeira - Brazil

^[5] Univ Estadual Campinas, Sch Appl Sci, Lab Mol Biol Exercise, Limeira - Brazil

^[6] Univ Estadual Campinas, Sch Appl Sci, Multidisciplinary Lab Food & Hlth, Limeira - Brazil

^[7] Fed Univ Espirito, Dept Integrated Hlth Educ, Vitoria, ES - Brazil

^[8] Univ Sao Paulo, Sch Phys Educ & Sport Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[9] Massachusetts Coll Pharm & Hlth Sci MCPHS Univ, Boston, MA - USA

^[10] Harvard Med Sch, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 - USA

^[11] Univ Fed Sergipe, Dept Physiol, Sao Cristovao, Sergipe - Brazil

• Document type: Journal article
• Source: Trials; v. 22, n. 1 DEC 18 2021.
• Web of Science Citations: 0

Abstract

The low-grade inflammation is pivotal in obesity and its comorbidities; however, the inflammatory proteins are out of target for traditional drug therapy. Omega-3 (omega 3) fatty acids can modulate the downstream signaling of Toll-like receptor (TLR) and tumor necrosis factor-alpha receptor (TNF alpha) through GPR120, a G-protein-coupled receptor, a mechanism not yet elucidated in humans. This work aims to investigate if the omega 3 supplementation, at a feasible level below the previously recommended level in the literature, is enough to disrupt the inflammation and endoplasmic reticulum stress (ER-stress), and also if in acute treatment (3 h) omega 3 can activate the GPR120 in peripheral blood mononuclear cells (PBMC) and leukocytes from overweight non-alcoholic fatty liver disease (NAFLD) participants. The R270H variant of the Ffar4 (GPR120 gene) will also be explored about molecular responses and blood lipid profiles. A triple-blind, prospective clinical trial will be conducted in overweight men and women, aged 19-75 years, randomized into placebo or supplemented (2.2 g of omega 3 {[}EPA+DHA]) groups for 28 days. For sample calculation, it was considered the variation of TNF alpha protein and a 40% dropout rate, obtaining 22 individuals in each group. Volunteers will be recruited among patients with NAFLD diagnosis. Anthropometric parameters, food intake, physical activity, total serum lipids, complete fatty acid blood profile, and glycemia will be evaluated pre- and post-supplementation. In the PBMC and neutrophils, the protein content and gene expression of markers related to inflammation (TNF alpha, MCP1, IL1 beta, IL6, IL10, JNK, and TAK1), ER-stress (ATF1, ATF6, IRE1, XBP1, CHOP, eIF2 alpha, eIF4, HSP), and omega 3 pathway (GPR120, beta-arrestin2, Tab1/2, and TAK1) will be evaluated using Western blot and RT-qPCR. Participants will be genotyped for the R270H (rs116454156) variant using the TaqMan assay. It is hypothesized that attenuation of inflammation and ER-stress signaling pathways in overweight and NAFLD participants will be achieved through omega 3 supplementation through binding to the GPR120 receptor. (AU)

• FAPESP's process: 12/07129-6 - W3 and W9 fatty acids as inflammatory pathway blockers through GPR120 receptor: a multi-organic approach
• Grantee: Dennys Esper Corrêa Cintra
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center
• Grantee: Licio Augusto Velloso
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC