|Perrard, Xiao-yuan Dai|
Submitted to: Circulation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/27/2007
Publication Date: 2/27/2007
Citation: Wu, H., Ghosh, S., Perrard, X.D., Feng, L., Garcia, G.E., Perrard, J.L., Sweeney, J.F., Peterson, L.E., Chan, L., Smith, C.W., Ballantyne, C.M. 2007. T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity. Circulation. 115(80):1029-1038. Interpretive Summary: This manuscript demonstrates for the first time the increase in T cell lymphocytes in adipose tissue of animals on a high-fat diet, and the occurrence of T cells in adipose tissue of obese humans. The problem being addressed is that obesity has associated inflammation that contributes to complications such as atherosclerosis, liver and kidney injury and dysfunction. Lymphocytes are known to release inflammatory mediators that can promote tissue injury. In addition, this manuscript demonstrates for the first time the production of a protein called CCL5 produced by adipose tissue that has the ability to attract and activate T cells. This protein is increased in the blood of obese humans and animals, and the impact of this work is that this protein may be a sensitive marker for impending inflammatory complications of diet-induced obesity.
Technical Abstract: Obesity is associated with chronic inflammation, which includes increased macrophage accumulation in adipose tissue (AT) and upregulation of chemokines and cytokines. T cells also play important roles in chronic inflammatory diseases such as atherosclerosis but have not been well studied in obesity. Flow cytometric analysis showed higher numbers of T cells and macrophages in AT of diet-induced obese insulin-resistant male mice than in lean mice and obese females (P<0.05). RNase protection assay, ELISA, and flow cytometry indicated gender-dependent upregulation of mRNA and protein levels of regulated on activation, normal T cell expressed and secreted (RANTES) and its receptor CCR5 in AT of obese mice. Adipocytes, stromal/vascular cells from mouse AT, and human and murine adipocytes expressed RANTES. RANTES mRNA levels were negatively correlated with adiponectin in mouse AT. Adiponectin-deficient mice fed high-fat diet showed higher RANTES mRNA levels in AT than wild-type mice. Activated T cells coincubated with preadipocytes in vitro significantly suppressed preadipocyte-to-adipocyte differentiation. Obese humans with metabolic syndrome had higher mRNA levels of RANTES and CCR5 in subcutaneous AT than lean humans. RANTES and CCR5 mRNA levels were significantly higher in visceral than subcutaneous AT of morbidly obese humans. RANTES mRNA levels were positively correlated with CD3 and CD11b in human visceral AT. Obesity is associated with increased accumulation of T cells and macrophages in AT, which may play important roles in obesity-related disease by influencing preadipocyte/adipocyte functions. RANTES is an adipokine that is upregulated in AT by obesity in both mice and humans.