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

Objectives: High-fat diet (HFD) feeding in mice is characterized by accumulation of alpha beta T cells in adipose tissue. However, the contribution of alpha beta 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 alpha beta T cells on insulin sensitivity and inflammatory state of skeletal muscle and adipose tissue in obesity. Furthermore, we investigated whether CD4+IFN gamma+(T(H)1) cells are involved in skeletal muscle and adipose tissue metabolic dysfunction that accompanies obesity. Methods: Mice lacking alpha beta 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 T(H)1 cells on skeletal muscle and adipose tissue inflammation and metabolic functions, we injected 5 x 10(5) T(H)1 cells or PBS weekly over 12 weeks into HFD-fed TCRb-/- mice. We also cultured C2C12 myofibers and 3T3-L1 adipocytes with T(H)1conditioned medium. Results: We showed that similar to adipose tissue, skeletal muscle of obese mice have higher alpha beta 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 wildtype 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 T(H)1 cells. Our results suggest an important role of T(H)1 cells in regulating inflammation and insulin resistance in obesity. (C) 2014 Elsevier Ireland Ltd. All rights reserved.