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


ABSTRACT: OBJECTIVES:High-fat diet (HFD) feeding in mice is characterized by accumulation of ?? T cells in adipose tissue. However, the contribution of ?? 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 ?? T cells on insulin sensitivity and inflammatory state of skeletal muscle and adipose tissue in obesity. Furthermore, we investigated whether CD4+IFN?+ (TH1) cells are involved in skeletal muscle and adipose tissue metabolic dysfunction that accompanies obesity. METHODS:Mice lacking ?? 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 ?? 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.

SUBMITTER: Khan IM 

PROVIDER: S-EPMC4094239 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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

Khan Ilvira M IM   Dai Perrard Xiao-Yuan XY   Perrard Jerry L JL   Mansoori Amir A   Wayne Smith C C   Wu Huaizhu H   Ballantyne Christie M CM  

Atherosclerosis 20140121 2


<h4>Objectives</h4>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  ...[more]

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