Published online before print February 12, 2007, doi: 10.1161/CIRCULATIONAHA.106.638379
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(Circulation. 2007;115:1029-1038.)
© 2007 American Heart Association, Inc.
Molecular Cardiology |
T-Cell Accumulation and Regulated on Activation, Normal T Cell Expressed and Secreted Upregulation in Adipose Tissue in Obesity
From the Section of Atherosclerosis and Vascular Medicine (H.W., S.G., X.D.P., J.L.P., C.M.B.), the Division of Nephrology (L.F., G.E.G.), and the Division of Diabetes, Endocrinology and Metabolism (L.C.), Department of Medicine; the Section of Leukocyte Biology (C.W.S.), Department of Pediatrics; the Division of General Surgery (J.F.S.), Department of Surgery, Baylor College of Medicine, Houston, Tex; the Department of Public Health (L.E.P.), The Methodist Hospital, and the Center for Cardiovascular Disease Prevention (C.M.B.), Methodist DeBakey Heart Center, Houston, Tex; and the National Institute of Nutrition (S.G.), Jamai Osmania PO, Hyderabad, India.
Correspondence to Dr Christie M. Ballantyne, Baylor College of Medicine, 6565 Fannin, Mailstop A-601, Houston, TX 77030. E-mail cmb{at}bcm.tmc.edu
Received May 8, 2006; accepted December 11, 2006.
Background— 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.
Methods and Results— 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.
Conclusions— 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.
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