Dietary n-3 Polyunsaturated Fatty Acids (PUFA) Decrease Obesity-Associated Th17 Cell-Mediated Inflammation during Colitis

作者：Monk Jennifer M; Hou Tim Y; Turk Harmony F; Weeks Brad; Wu Chaodong; McMurray David N; Chapkin Robert S^*

来源：PLos One, 2012, 7(11): e49739.

DOI：10.1371/journal.pone.0049739

Clinical and experimental evidence suggests that obesity-associated inflammation increases disease activity during colitis, attributed in part to the effects of Th17 cells. Using a model of concurrent obesity and colitis, we monitored changes in critical immune cell subsets and inflammatory biomarker expression in three key tissues: visceral adipose tissue, colon (local inflammatory site) and spleen (systemic inflammatory site), and we hypothesized that n-3 PUFA would reduce the percentage of inflammatory immune cell subsets and suppress inflammatory gene expression, thereby improving the disease phenotype. Obesity was induced in C57BL/6 mice by feeding a high fat (HF) diet (59.2% kcal) alone or an isocaloric HF diet supplemented with fish oil (HF-FO) for 12 weeks. Colitis was induced via a 2.5% trinitrobenzene sulfonic acid (TNBS) enema. The HF-FO diet improved the obese phenotype by reducing i) serum hormone concentrations (leptin and resistin), ii) adipose tissue mRNA expression of inflammatory cytokines (MCP-1, IFN gamma, IL-6, IL17F and IL-21) and iii) total (F4/80(+) CD11b(+)) and inflammatory adipose tissue M1 (F4/80(+) CD11c(+)) macrophage content compared to HF (P<0.05). In addition, the HF-FO diet reduced both colitis-associated disease severity and colonic mRNA expression of the Th17 cell master transcription factor (ROR gamma tau) and critical cytokines (IL-6, IL-17A, IL-17F, IL-21, IL-23 and IFN gamma) versus HF (P<0.05). Compared to HF, the percentage of both splenic Th17 and Th1 cells were reduced by the HF-FO group (P<0.05). Under ex vivo polarizing conditions, the percentage of HF-FO derived CD4(+) T cells that reached Th17 cell effector status was suppressed (P = 0.05). Collectively, these results indicate that n-3 PUFA suppress Th1/Th17 cells and inflammatory macrophage subsets and reconfigure the inflammatory gene expression profile in diverse tissue sites in obese mice following the induction of colitis.

• 出版日期2012-11-16