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

Trials

Jose Luis Marques-Rocha¹  Enilton Aparecido Camargo²  Ellencristina Silva Batista³  Leandro Pereira de Moura⁴  José Rodrigo Pauli⁵  Eduardo Rochete Ropelle⁵  Vitor Rosetto Muñoz⁵  Roberta Lara⁶  Thaiane da Silva Rios⁷  Susana Castelo Branco Ramos Nakandakari⁷  Dennys Esper Cintra⁷  Rania Angelina Mekary⁸  Diogo Thimóteo da Cunha⁹  Marcel Monteiro Vasconcelos^1,10  Joyce Santos Jesus^1,10  Adelino Sanchez Ramos da Silva^1,11 

[1] Department of Integrated Health Education, Federal University of Espírito Santo, Vitoria, Brazil;Department of Physiology, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil;Graduate Program of Health Sciences (PPGCS), Federal University of Sergipe, Aracaju, Sergipe, Brazil;Laboratory of Nutritional Genomics, School of Applied Sciences, University of Campinas, Pedro Zaccaria, 1300 Zip, 13484-350, Limeira, Brazil;Nutrition Department, Federal University of Sergipe, Lagarto, Sergipe, Brazil;Lipids and Nutrigenomics Research Center, School of Applied Sciences, University of Campinas, Limeira, Brazil;Laboratory of Molecular Biology of Exercise, School of Applied Sciences, University of Campinas, Limeira, Brazil;Laboratory of Molecular Biology of Exercise, School of Applied Sciences, University of Campinas, Limeira, Brazil;Lipids and Nutrigenomics Research Center, School of Applied Sciences, University of Campinas, Limeira, Brazil;Laboratory of Nutritional Genomics, School of Applied Sciences, University of Campinas, Pedro Zaccaria, 1300 Zip, 13484-350, Limeira, Brazil;Laboratory of Nutritional Genomics, School of Applied Sciences, University of Campinas, Pedro Zaccaria, 1300 Zip, 13484-350, Limeira, Brazil;Lipids and Nutrigenomics Research Center, School of Applied Sciences, University of Campinas, Limeira, Brazil;Massachusetts College of Pharmacy and Health Sciences (MCPHS) University, Boston, MA, USA;Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA;Multidisciplinary Laboratory of Food and Health, School of Applied Sciences, University of Campinas, Limeira, Brazil;Nutrition Department, Federal University of Sergipe, Lagarto, Sergipe, Brazil;School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil;

关键词: Overweight;    GPR120;    Omega-3;    Inflammation;    Endoplasmic reticulum stress;    NAFLD;   

DOI  :  10.1186/s13063-021-05702-x

来源: Springer

【 摘 要 】

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 (ω3) fatty acids can modulate the downstream signaling of Toll-like receptor (TLR) and tumor necrosis factor-α receptor (TNFα) through GPR120, a G-protein-coupled receptor, a mechanism not yet elucidated in humans. This work aims to investigate if the ω3 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) ω3 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 ω3 [EPA+DHA]) groups for 28 days. For sample calculation, it was considered the variation of TNFα 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 (TNFα, MCP1, IL1β, IL6, IL10, JNK, and TAK1), ER-stress (ATF1, ATF6, IRE1, XBP1, CHOP, eIF2α, eIF4, HSP), and ω3 pathway (GPR120, β-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 ω3 supplementation through binding to the GPR120 receptor.Trial registrationClinicalTrials.gov #RBR-7x8tbx. Registered on May 10, 2018, with the Brazilian Registry of Clinical Trials.

【 授权许可】

CC BY