title: T-cell recruitment and Th1 polarization in adipose tissue during diet-induced obesity in C57BL/6 mice.
abstract: The role of adaptive immunity in obesity-associated adipose tissue (AT) inflammation and insulin resistance (IR) is controversial. We employed flow cytometry and quantitative PCR to assess T-cell recruitment and activation in epididymal AT (eAT) of C57BL/6 mice during 4-22 weeks of a high-fat diet (HFD (60% energy)). By week 6, eAT mass and stromal vascular cell (SVC) number increased threefold in mice fed HFD, coincident with onset of IR. We observed no increase in the proportion of CD3(+) SVCs or in gene expression of CD3, interferon-γ (IFN-γ), or regulated upon activation, normal T-cell expressed and secreted (RANTES) during the first 16 weeks of HFD. In contrast, CD11c(+) macrophages (MΦ) were enriched sixfold by week 8 (P < 0.01). SVC enrichment for T cells (predominantly CD4(+) and CD8(+)) and elevated IFN-γ and RANTES gene expression were detected by 20-22 weeks of HFD (P < 0.01), coincident with the resolution of eAT remodeling. HFD-induced T-cell priming earlier in the obesity time course is suggested by (i) elevated (fivefold) interleukin-12 (IL-12)p40 gene expression in eAT by week 12 (P ≤ 0.01) and (ii) greater IFN-γ secretion from phorbol myristate acetate (PMA)/ionophore-stimulated eAT explants at week 6 (onefold, P = 0.08) and week 12 (fivefold, P < 0.001). In conclusion, T-cell enrichment and IFN-γ gene induction occur subsequent to AT macrophage (ATMΦ) recruitment, onset of IR and resolution of eAT remodeling. However, enhanced priming for IFN-γ production suggests the contribution of CD4(+) and/or CD8(+) effectors to cell-mediated immune responses promoting HFD-induced AT inflammation and IR.
authors.affiliation: Obesity and Metabolism Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA. katherine.strissel@tufts.edu
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Strissel
authors.forename: Jason
authors.initials: J
authors.lastname: DeFuria
authors.forename: Merav E
authors.initials: ME
authors.lastname: Shaul
authors.forename: Grace
authors.initials: G
authors.lastname: Bennett
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Greenberg
authors.forename: Martin S
authors.initials: MS
authors.lastname: Obin
mesh_terms: D000273:Adipose Tissue / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects; D015870:Gene Expression; D007249:Inflammation / Q000209:etiology* / Q000276:immunology; D007333:Insulin Resistance; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000378:metabolism*
chemical_list: D039521:CD11c Antigen; D017252:CD3 Complex; D018946:Chemokine CCL5; D004041:Dietary Fats; D053762:Interleukin-12 Subunit p40; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate