T-cell recruitment and Th1 polarization in adipose tissue during diet-induced obesity in C57BL/6 mice

Obesity (Silver Spring). 2010 Oct;18(10):1918-25. doi: 10.1038/oby.2010.1. Epub 2010 Jan 28.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adipose Tissue / immunology*
  • Adipose Tissue / metabolism
  • Animals
  • CD11c Antigen / metabolism
  • CD3 Complex / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism
  • Dietary Fats / adverse effects
  • Gene Expression
  • Inflammation / etiology*
  • Inflammation / immunology
  • Insulin Resistance*
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-12 Subunit p40 / genetics
  • Interleukin-12 Subunit p40 / metabolism
  • Lymphocyte Activation
  • Macrophages / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / etiology
  • Obesity / immunology*
  • Obesity / metabolism
  • T-Lymphocytes / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Th1 Cells / metabolism*


  • CD11c Antigen
  • CD3 Complex
  • Chemokine CCL5
  • Dietary Fats
  • Interleukin-12 Subunit p40
  • Interferon-gamma
  • Tetradecanoylphorbol Acetate