Attenuated adipose tissue and skeletal muscle inflammation in obese mice with combined CD4+ and CD8+ T cell deficiency
| Autor: | Amir Mansoori, Christie M. Ballantyne, Jerry L. Perrard, Ilvira M. Khan, Huaizhu Wu, Xiao Yuan Dai Perrard, C. Wayne Smith |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
CD4-Positive T-Lymphocytes
medicine.medical_specialty Receptors Antigen T-Cell alpha-beta Glucose uptake Adipose tissue macrophages Muscle Fibers Skeletal Adipose tissue Inflammation White adipose tissue CD8-Positive T-Lymphocytes Biology Article Cell Line Interferon-gamma Mice Insulin resistance T-Lymphocyte Subsets 3T3-L1 Cells Lymphopenia Internal medicine medicine Animals Cytotoxic T cell Obesity Muscle Skeletal Hypertriglyceridemia Mice Knockout Myositis Gene Expression Profiling Skeletal muscle Th1 Cells medicine.disease Adoptive Transfer Dietary Fats Mice Inbred C57BL Endocrinology medicine.anatomical_structure Adipose Tissue Culture Media Conditioned Hyperglycemia Insulin Resistance medicine.symptom Cardiology and Cardiovascular Medicine |
| Zdroj: | Atherosclerosis. 233:419-428 |
| ISSN: | 0021-9150 |
| Popis: | 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.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.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.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. |
| Databáze: | OpenAIRE |
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