Attenuated adipose tissue and skeletal muscle inflammation in obese mice with combined CD4+ and CD8+ T cell deficiency

Atherosclerosis. 2014 Apr;233(2):419-428. doi: 10.1016/j.atherosclerosis.2014.01.011. Epub 2014 Jan 21.


Objectives: High-fat diet (HFD) feeding in mice is characterized by accumulation of αβ T cells in adipose tissue. However, the contribution of αβ T cells to obesity-induced inflammation of skeletal muscle, a major organ of glucose uptake, is unknown. This study was undertaken to evaluate the effect of αβ T cells on insulin sensitivity and inflammatory state of skeletal muscle and adipose tissue in obesity. Furthermore, we investigated whether CD4+IFNγ+ (TH1) cells are involved in skeletal muscle and adipose tissue metabolic dysfunction that accompanies obesity.

Methods: Mice lacking αβ T cells (T cell receptor beta chain-deficient [TCRb-/-] mice) were fed HFD for 12 weeks. Obesity-induced skeletal muscle and adipose tissue inflammation was assessed by flow cytometry and quantitative RT-PCR. To investigate the effect of TH1 cells on skeletal muscle and adipose tissue inflammation and metabolic functions, we injected 5×10(5) TH1 cells or PBS weekly over 12 weeks into HFD-fed TCRb-/- mice. We also cultured C2C12 myofibers and 3T3-L1 adipocytes with TH1-conditioned medium.

Results: We showed that similar to adipose tissue, skeletal muscle of obese mice have higher αβ T cell content, including TH1 cells. TCRb-/- mice were protected against obesity-induced hyperglycemia and insulin resistance. We also demonstrated suppressed macrophage infiltration and reduced inflammatory cytokine expression in skeletal muscle and adipose tissue of TCRb-/- mice on HFD compared to wild-type obese controls. Adoptive transfer of TH1 cells into HFD-fed TCRb-/- mice resulted in increased skeletal muscle and adipose tissue inflammation and impaired glucose metabolism. TH1 cells directly impaired functions of C2C12 myotubes and 3T3-L1 adipocytes in vitro.

Conclusions: We conclude that reduced adipose tissue and skeletal muscle inflammation in obese TCRb-/- mice is partially attributable to the absence of TH1 cells. Our results suggest an important role of TH1 cells in regulating inflammation and insulin resistance in obesity.

Keywords: Inflammation; Obesity; Skeletal muscle; T cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3T3-L1 Cells
  • Adipose Tissue / immunology
  • Adipose Tissue / pathology*
  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Culture Media, Conditioned
  • Dietary Fats / toxicity
  • Gene Expression Profiling
  • Hyperglycemia / etiology
  • Hyperglycemia / metabolism
  • Hyperglycemia / pathology
  • Hypertriglyceridemia / etiology
  • Hypertriglyceridemia / metabolism
  • Hypertriglyceridemia / pathology
  • Insulin Resistance
  • Interferon-gamma / physiology
  • Lymphopenia / complications
  • Lymphopenia / immunology
  • Lymphopenia / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle Fibers, Skeletal
  • Muscle, Skeletal / immunology
  • Muscle, Skeletal / pathology*
  • Myositis / etiology
  • Myositis / immunology
  • Myositis / prevention & control*
  • Obesity / complications
  • Obesity / immunology
  • Obesity / pathology*
  • Receptors, Antigen, T-Cell, alpha-beta / analysis
  • Receptors, Antigen, T-Cell, alpha-beta / deficiency
  • T-Lymphocyte Subsets / immunology*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th1 Cells / transplantation


  • Culture Media, Conditioned
  • Dietary Fats
  • Receptors, Antigen, T-Cell, alpha-beta
  • Interferon-gamma