title: Attenuated adipose tissue and skeletal muscle inflammation in obese mice with combined CD4+ and CD8+ T cell deficiency.
abstract: OBJECTIVE
  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.
authors: Division of Atherosclerosis and Vascular Medicine, Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, USA.
authors: Ilvira M
authors: IM
authors: Khan
authors: Division of Atherosclerosis and Vascular Medicine, Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors: Xiao-Yuan
authors: XY
authors: Dai Perrard
authors: Division of Atherosclerosis and Vascular Medicine, Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors: Jerry L
authors: JL
authors: Perrard
authors: Division of Atherosclerosis and Vascular Medicine, Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors: Amir
authors: A
authors: Mansoori
authors: Section of Leukocyte Biology, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors: C
authors: C
authors: Wayne Smith
authors: Division of Atherosclerosis and Vascular Medicine, Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Section of Leukocyte Biology, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors: Huaizhu
authors: H
authors: Wu
authors: Division of Atherosclerosis and Vascular Medicine, Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Section of Leukocyte Biology, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. Electronic address: cmb@bcm.tmc.edu.
authors: Christie M
authors: CM
authors: Ballantyne
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000276:immunology / Q000473:pathology*; D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D017077:Culture Media, Conditioned; D004041:Dietary Fats / Q000633:toxicity; D020869:Gene Expression Profiling; D006943:Hyperglycemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D015228:Hypertriglyceridemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D007371:Interferon-gamma / Q000502:physiology; D008231:Lymphopenia / Q000150:complications / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal; D018482:Muscle, Skeletal / Q000276:immunology / Q000473:pathology*; D009220:Myositis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D009765:Obesity / Q000150:complications / Q000276:immunology / Q000473:pathology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000172:deficiency; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation
chemical_list: D017077:Culture Media, Conditioned; D004041:Dietary Fats; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma
keywords: Inflammation; Obesity; Skeletal muscle; T cells