Anti‐inflammatory and anti‐chemotactic effects of dietary flaxseed oil on CD8+ T cell/adipocyte‐mediated cross‐talk

• Published in: Molecular nutrition & food research 2016-03, Vol.60 (3), p.621-630
• Main Authors: Monk, Jennifer M, Liddle, Danyelle M, Brown, Morgan J, Zarepoor, Leila, Boer, Anna A, Ma, David W. L, Power, Krista A, Robinson, Lindsay E
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; alpha-linolenic acid; Animals; anti-inflammatory activity; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; CD8+ T cells; CD8-positive T-lymphocytes; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - metabolism; Cell Communication - drug effects; chemoattractants; chemokine CCL3; chemokine CCL4; chemokine CCL5; chemotaxis; Chemotaxis - drug effects; coculture; Coculture Techniques; corn oil; diet; Dietary Fats, Unsaturated - pharmacology; endotoxins; Fatty Acids - metabolism; Fatty Acids, Omega-3 - pharmacology; Flaxseed oil; Gene Expression Regulation - drug effects; interleukin-1beta; interleukin-6; linseed oil; Linseed Oil - pharmacology; Lipopolysaccharides - pharmacology; macrophages; Male; mice; Mice, Inbred C57BL; Obesity; omega-3 fatty acids; Paracrine cross-talk; phenotype; secretion; signal transduction; transcription factor NF-kappa B; tumor necrosis factor-alpha
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201500541

SCOPE: CD8⁺ T cell/adipocyte paracrine interactions represent a critical step in the development of the obese inflammatory phenotype that is disrupted by long‐chain n‐3 PUFA. Our objective was to determine the effect of flaxseed‐derived n‐3 PUFA (α‐linolenic acid) on these paracrine interactions. METHODS AND RESULTS: C57BL/6 mice were fed 3.5% flaxseed oil (FX) + 3.5% corn oil diet w/w or an isocaloric 7% corn oil w/w control diet (CON) for 3 wk. 3T3‐L1 adipocytes and purified primary splenic CD8⁺ T cells were cocultured at an obese cellular ratio (10% CD8⁺ T cells) and LPS‐stimulated (10 ng/mL mimicking obese circulating endotoxin levels) for 24 h. FX cocultures reduced (i) secreted IL‐6, tumor necrosis factor α (TNF‐α), macrophage chemoattractant protein 1 (MCP‐1), macrophage inflammatory protein 1α (MIP‐1α), and RANTES (regulated on activation, normal T cell expressed and secreted) levels; (ii) activation of inflammatory transcription factors NFκB (nuclear factor kappa‐light‐chain‐enhancer of activated B cell) p65 and signal transducer and activator of transcription‐3 (STAT3); and (iii) RAW264.7 macrophage chemotaxis versus CON (p ≤ 0.05). Coculture of pre‐inflamed adipocytes (10 ng/mL LPS, 24 h prior to CD8⁺ T‐cell addition) resulted in reduced secretion of IL‐6, IL‐1β, MCP‐1, MCP‐3, MIP‐1β, and RANTES in FX cocultures versus CON (p ≤ 0.05). CONCLUSION: FX exerts an anti‐chemotactic and anti‐inflammatory effect on CD8⁺ T cell/adipocyte paracrine interactions (cross‐talk), which has the potential to mitigate macrophage chemotaxis which drives components of the obese phenotype.