Obese adipose tissue (AT) inflammation is partly driven by accumulation of CD4⁺ T helper (Th)1 cells and reduced Th2 and T regulatory (Treg) subsets, which promotes macrophage chemotaxis and ensuing AT metabolic dysfunction. This study investigated CD4⁺ T cell/adipocyte cytokine-mediated paracrine interactions (cross-talk) as a target for dietary intervention to mitigate obese AT inflammation. Using an in vitro co-culture model designed to recapitulate CD4⁺ T cell accumulation in obese AT (5% of stromal vascular cellular fraction), 3 T3-L1 adipocytes were co-cultured with purified splenic CD4⁺ T cells from C57Bl/6 mice consuming one of two isocaloric diets containing either 10% w/w safflower oil (control, CON) or 7% w/w safflower oil+3% w/w fish oil (FO) for 4 wk. (n=8–11/diet). The FO diet provided 1.9% kcal from the long-chain (LC) n-3 polyunsaturated fatty acids (PUFA) EPA and DHA, a dose that can be achieved by supplementation. Co-cultures were stimulated for 48 h with lipopolysaccharide (LPS) to mimic in vivo obese endotoxin levels, or with conditioned media collected from LPS-stimulated visceral AT isolated from CON-fed mice. In both stimulation conditions, FO reduced mRNA expression and/or secreted protein levels of Th1 markers (T-bet, IFN-γ) and increased Th2 markers (GATA3, IL-4), concomitant with reduced inflammatory cytokines (IL-1β, IL-6, IL-12p70, TNF-α), macrophage chemokines (MCP-1, MCP-3, MIP-1α, MIP-2), and levels of activated central regulators of inflammatory signaling (NF-κB, STAT-1, STAT-3) (P<.05). Therefore, CD4⁺ T cell/adipocyte cross-talk represents as a potential target for LC n-3 PUFA to mitigate obese AT inflammation.

肥胖脂肪组织（AT）的炎症部分是由CD4 ⁺ T辅助（Th）1细胞的积累以及Th2和T调节（Treg）子集减少引起的，这促进了巨噬细胞的趋化性并导致AT代谢功能障碍。这项研究调查了CD4 ⁺ T细胞/脂肪细胞细胞因子介导的旁分泌相互作用（串扰）作为饮食干预减轻肥胖AT炎症的目标。使用旨在概括肥胖AT（基质血管细胞分数的5％）中CD4 ⁺ T细胞积累的体外共培养模型，将3枚T3-L1脂肪细胞与来自C57Bl / 6小鼠的纯化脾CD4 ⁺ T细胞共培养食用两种等热量饮食中的一种，其中两种饮食的含量均为10％w / w红花油（对照，CON）或7％w / w红花油+ 3％w / w鱼油（FO），连续4周。（n = 8-11 /饮食）。FO饮食从长链（LC）n-3多不饱和脂肪酸（PUFA）EPA和DHA中提供了1.9％kcal，该剂量可以通过补充获得。用脂多糖（LPS）刺激共培养48小时以模拟体内肥胖内毒素水平，或使用从CON喂养的小鼠中分离的LPS刺激的内脏AT收集的条件培养基。在两种刺激条件下，FO均可降低Th1标记（T-bet，IFN-γ）的mRNA表达和/或分泌的蛋白质水平，并增加Th2标记（GATA3，IL-4），并伴有炎性细胞因子（IL-1β，IL）减少-6，IL-12p70，TNF-α），巨噬细胞趋化因子（MCP-1，MCP-3，MIP-1α，MIP-2）和激活的炎症信号中央调节剂（NF-κB，STAT-1， STAT-3）（P <.05）。因此，CD4 ⁺ T细胞/脂肪细胞的串扰代表LC n-3 PUFA减轻肥胖AT炎症的潜在目标。