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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #307517
Title: Attenuated adipose tissue and skeletal muscle inflammation in obese mice with combined CD4+ and CD8+ T cell deficiency

Author
item KHAN, ILVIRA - Baylor College Of Medicine
item PERRARD, XIAO-YUAN DAI - Baylor College Of Medicine
item PERRARD, JERRY - Baylor College Of Medicine
item MANSOORI, AMIR - Baylor College Of Medicine
item SMITH, CLIFTON - Children'S Nutrition Research Center (CNRC)
item WU, HUAIZHU - Baylor College Of Medicine
item BALLANTYNE, CHRISTIE - Baylor College Of Medicine

Submitted to: Atherosclerosis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/9/2014
Publication Date: 1/21/2014
Citation: Khan, I.M., Perrard, X., Perrard, J.L., Mansoori, A., Smith, C.W., Wu, H., Ballantyne, C.M. 2014. Attenuated adipose tissue and skeletal muscle inflammation in obese mice with combined CD4+ and CD8+ T cell deficiency. Atherosclerosis. 233(2):419-428.

Interpretive Summary: Diet-induced obesity in mice results in migration of some types of white blood cells into fat tissues and skeletal muscle. This study investigated the importance of one type of white blood cell, scientifically called Th1 cells, in causing obesity-related tissue inflammation. These normally help protect against infection, but can also cause inflammation. Our studies provide strong evidence that these cells participate in causing fat tissue and skeletal muscle inflammation, and symptoms of diabetes in obese mice.

Technical Abstract: High-fat diet feeding in mice is characterized by accumulation of alpha Beta Y+T cells in adipose tissue. However, the contribution of ab 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+IFNY+ (TH1) cells are involved in skeletal muscle and adipose tissue metabolic dysfunction that accompanies obesity. Mice lacking alpha Beta T cells (T cell receptor beta chain-deficient [TCRb-/-] mice) were fed high dfat diet 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 x 105 TH1 cells or PBS weekly over 12 weeks into high fat diet-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 ab 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. 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.