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J Nutr Biochem. 2018 Mar;53:9-19. doi: 10.1016/j.jnutbio.2017.09.015. Epub 2017 Oct 18.

Flaxseed oil rich in omega-3 protects aorta against inflammation and endoplasmic reticulum stress partially mediated by GPR120 receptor in obese, diabetic and dyslipidemic mice models.

Author information

1
Laboratory of Nutritional Genomics, School of Applied Sciences of University of Campinas Limeira, São Paulo, Brazil.
2
Lipids Laboratory (LIM10), Faculty of Medical Sciences of University of São Paulo, São Paulo, Brazil.
3
Laboratory of Cell Signaling, Faculty of Medical Sciences of University of Campinas, São Paulo, Brazil.
4
INNOVARE Biomarkers Laboratory, Faculty of Medical Sciences of University of Campinas, São Paulo, Brazil.
5
School of Physical Education and Sport of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
6
Laboratory of Molecular Biology of Exercise, School of Applied Sciences of University of Campinas Limeira, São Paulo, Brazil.
7
Laboratory of Nutritional Genomics, School of Applied Sciences of University of Campinas Limeira, São Paulo, Brazil; Nutrigenomics and Lipids Center, School of Applied Sciences of University of Campinas Limeira, São Paulo, Brazil. Electronic address: dcintra@yahoo.com.

Abstract

The "first hit" to atherogenesis is driven by toll-like receptor 4, endoplasmic reticulum stress and ultimately metabolic dysfunction. In this study, we hypothesized that a flaxseed oil-enriched diet (FS) abolishes these inflammatory signaling pathway and restore metabolic homeostasis by activating the fatty acid receptor GPR120 in aorta of obese mice. Glucose homeostasis was assessed by GTT and ITT; lipidomics was performed using a Hybrid Ion Trap-Orbitrap Mass Spectrometer; serum lipids were measured using colorimetric assays; GPR120 and infiltrating macrophages were analyzed by immunofluorescence; protein immunoprecipitation and gene expression were evaluated by Western blot and RT-PCR, respectively. There were no differences in body weight and food intake between the groups from both strains (Swiss and LDLr-KO mice). GTT and cholesterol levels were improved by FS in both mice models. Lipidomics showed an increase in ω3 (C18:3) content, meanwhile stearic acid (C18:0) was not detected in endothelial tissue in response to FS. Moreover, FS markedly decreased pro-inflammatory (IL-1β, TNF-α, pIκBα, pIKKβ) and unfolded protein response markers (ATF6 and GRP78) in aorta. In Swiss mice, GPR120 was partially involved in the ω3-mediated anti-inflammatory actions, disrupting TLR4 pathway, but not in LDLr-KO mice. Partial replacement of dietary saturated by unsaturated ω3 fatty acids contributes to inhibition of cardiovascular risk markers, pro-inflammatory cytokines and ER stress sensors and effectors in the aorta. However, downregulation of inflammation is not mediated by arterial GPR120 activation.

KEYWORDS:

Atherogenesis; ER stress; GPR120; Inflammation; Nutrigenomics; Obesity; n-3 fatty acids

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