The modulation of inflammatory adipokines by n-3 and n-6 polyunsaturated fatty acids using in vitro models that mimic obese adipose tissue

Liddle, Danyelle M.
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University of Guelph

Obese adipose tissue (AT) is characterized by chronic low-grade inflammation, driven by changes in circulating endotoxin (lipopolysaccharide, LPS) and inflammatory adipokine-mediated cross-talk between adipocytes and AT-infiltrated immune cell populations, including CD8+ T cells. Evidence suggests that long-chain n-3 polyunsaturated fatty acids (PUFA) are anti-inflammatory nutrients, whereas few studies have explored the relative effects of n-6 PUFA or potential mechanisms underlying immunomodulation by n-3 and n-6 PUFA in conjunction with LPS. Findings in this thesis suggest that LC n-3 and n-6 PUFA differentially modulate inflammatory adipokine production within LPS-stimulated adipocytes via G protein-coupled 120- and Toll-like receptor (TLR) 4-dependent mechanisms, respectively. In LPS-stimulated CD8+ T cell/adipocyte co-cultures, our findings suggest that the anti-inflammatory action of LC n-3 PUFA versus n-6 PUFA was dependent on, in part, reduction of secreted tumour necrosis factor-α; a TLR4-induced inflammatory adipokine. Overall, this thesis supports LC n-3 PUFA as a nutritional strategy to mitigate AT inflammation.

obesity, adipose tissue, inflammatory adipokines, adipocytes, CD8+ T cells, macrophages, n-3 polyunsaturated fatty acids, n-6 polyunsaturated fatty acids, Toll-like receptor, NLRP3 inflammasome, GPR120