title: Dietary n-3 polyunsaturated fatty acids (PUFA) decrease obesity-associated Th17 cell-mediated inflammation during colitis.
abstract: 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, IFNγ, 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 (RORγτ) and critical cytokines (IL-6, IL-17A, IL-17F, IL-21, IL-23 and IFNγ) 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.
authors.affiliation: Program in Integrative Nutrition & Complex Diseases, Texas A&M University, College Station, Texas, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Monk
authors.forename: Tim Y
authors.initials: TY
authors.lastname: Hou
authors.forename: Harmony F
authors.initials: HF
authors.lastname: Turk
authors.forename: Brad
authors.initials: B
authors.lastname: Weeks
authors.forename: Chaodong
authors.initials: C
authors.lastname: Wu
authors.forename: David N
authors.initials: DN
authors.lastname: McMurray
authors.forename: Robert S
authors.initials: RS
authors.lastname: Chapkin
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000818:Animals; D003092:Colitis / Q000150:complications* / Q000178:diet therapy / Q000235:genetics / Q000276:immunology*; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D059305:Diet, High-Fat; D004041:Dietary Fats; D019587:Dietary Supplements; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology*; D020869:Gene Expression Profiling; D007249:Inflammation / Q000150:complications / Q000178:diet therapy / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D009765:Obesity / Q000150:complications*; D010641:Phenotype; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D016207:Cytokines; D004041:Dietary Fats; D015525:Fatty Acids, Omega-3