Dietary n-3 PUFA modulate CD4+ T cell subset markers, adipocyte antigen presentation potential and NLRP3 inflammasome activity in a co-culture model of obese adipose tissue
Danyelle M.Liddle Nutrition Available online 6 June 2021,
Highlights
• CD4+ T cell/adipocyte co-cultures mimicked obese adipose tissue pathophysiology
• Fish oil reduced adipocyte antigen presentation potential in co-culture
• Fish oil reduced adipocyte inflammasome priming and activity in co-culture
• Fish oil modulated markers of CD4+ T cell subsets in co-culture
• Fish oil reduced inflammatory CD4+ T cell/adipocyte cross-talk
Objective: Chronic low-grade inflammation in obesity is partly driven by inflammatory cross-talk between adipocytes and interferon (IFN)-γ-secreting CD4+ T helper (Th)1 cells; a process we showed may be mitigated by long-chain (LC) n-3 polyunsaturated fatty acids (PUFA). Our objective was to study pivotal mediators of Th1 cell/adipocyte interactions as potential mechanisms underlying LC n-3 PUFA anti-inflammatory effects. Research Methods & Procedures: Using an in vitro model, 3T3-L1 adipocytes were co-cultured with purified splenic CD4+ T cells from C57Bl/6 mice consuming one of two isocaloric high fat (HF) diets (60% kcal fat) containing either 41.2% kcal from lard + 18.7% kcal from corn oil (control, HF) or 41.2% kcal from lard + 13.4% kcal from corn oil + 5.3% kcal from fish oil (HF+FO). Co-cultures were stimulated for 48h with lipopolysaccharide (10 ng/mL). Results: Compared to HF co-cultures, HF+FO reduced Th1 cell markers (including secreted IFN-γ) and increased Th2 cell markers, consistent with reduced expression of major histocompatibility complex (MHC)II-related genes (P<0.05). HF+FO also blunted markers of NOD-like receptor family, pyrin domain containing (NLRP)3 inflammasome priming and activity (P<0.05). In confirmatory work, 3T3-L1 adipocyte pre-treatment with the LC n-3 PUFA docosahexaenoic acid (100 μM, 24h) blunted IFN-γ-induced (5 ng/mL, 24h) expression of MHCII-related genes and NLRP3 inflammasome priming and activity markers compared to control (P<0.05).
Conclusions: CD4+ T cell/adipocyte inflammatory interactions may provide a target for LC n-3 PUFA to mitigate obesity-associated inflammation.
