The atherosclerosis development requires additional
The atherosclerosis development requires additional pro-inflammatory response in the vascular tissue, promoting increased levels of adhesion molecules such as VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1). Cytokines such as TNF-α and IL-1β are able to upregulate these molecules, contributing to endothelial dysfunction and development of atherosclerosis and other inflammatory diseases , . During atherosclerosis progression, the accumulation of cholesterol in macrophages contribute to the formation of cholesterol crystals leading to inflammasome activation, and consequently the release of IL-1β and other proinflammatory cytokines , . Herein, mice fed with FS diet, especially the Swiss, had reduced aortic inflammatory and ER stress markers. Moreover, an increased expression of the anti-inflammatory cytokine IL-10 was observed in aortas from LDLr-KO mice. Altogether, these results indicate an attenuated inflammatory profile in the aortas of mice fed a FS diet. In fact, current findings show a remission of inflammation and stress-responsive signaling pathways by ω3. In 2012, Jung et al.  attributed to ω3-mediated IL 10 increase the main anti-inflammatory effects observed in the macrophages from the pmsf of HF fed mice. Spitler et al.  showed that suppression of ER stress led to recovery of endothelial contractile responses in aorta of hypertensive rats . Additionally, activation of unfolded protein response induced by chronic ER stress in arterial endothelium increases the susceptibility to atherogenesis .
Possibly, there are different receptors responsible for recognition and uptake of ω3 fatty acids into the cells. Although a number of receptors have been suggested to be involved in the metabolism of these fats, further studies are needed to clarify these questions. Wales et al. (2014)  showed an increase in resolvins in the arterial wall of APOE−/− mice fed with diets enriched with EPA and DHA. Resolvins can decrease inflammation by binding to its receptor; ChemR23 which activates Gαi/o, blocking TNF-α signaling via ERK . Alternatively, resolvins could bind to BLT1 (B-Leucotriene-1 receptor) and block the activation of adenylate cyclase and NF-κB signaling.
Interestingly, the expression of GPR120 was observed in the macrophages of the HF group, but its activation is dependent on the presence of unsaturated fatty acids (ALA, EPA, and DHA). Raptis et al. (2014)  detected GPR120 in Kupffer cells and showed hepatoprotective effects of ω3-fatty acids by modulating macrophage polarization towards M2 anti-inflammatory profile. We cannot rule out that, once activated by ω3-fatty acids, GPR120 may also contribute to M2 macrophage polarization in aorta, protecting the vascular tissue against atherogenesis.
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In mammals, adipose tissue serves as the principal store for lipids. White adipose tissue (WAT) stores triacylglycerol, which serves as the most efficient form of energy storage in times of energy excess. WAT plays a important role as an endocrine organ producing a variety of factors including leptin , adiponectin , and tumor necrosis factor α (TNFα) , which are thought to function in the regulation of metabolic homeostasis. Abnormal secretion of these factors often results in metabolic disorder. The major transcription factors of adipogenesis, including peroxisome proliferator-activated receptor-γ2 (PPAR-γ2) and CCAAT/enhancer binding protein α (C/EBPα), play a key role in complex transcriptional cascade during adipocyte differentiation . During periods of increased energy demand, hormones such as catecholamines activate lipolysis in adipocytes. The interaction of the hormones with G protein-coupled receptors (GPRs) increases the activity of adenylate cyclase, raises the level of adenosine 3′,5′-monophosphate (cAMP), and activates cAMP-dependent protein kinase (protein kinase A, PKA). Thus GPRs are important receptors for many aspects of cellular function. They are members of a large protein family that share common structural motifs such as seven transmembrane helices and can activate heterotrimeric G proteins, such as Gs, Gi, and Gq. Ligands bind specifically to the GPRs to stimulate and induce a variety of cellular responses via several second messenger pathways, for example, modulation of cAMP production, the phospholipase C pathway, ion channels, and mitogen-activated protein kinases .