Published online before print February 12, 2007, doi: 10.1161/CIRCULATIONAHA.106.638379
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(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.
CLINICAL PERSPECTIVE
This article has been cited by other articles:
 |
|
 |
|
  S. J van Dijk, E. J. Feskens, M. B Bos, D. W. Hoelen, R. Heijligenberg, M. G. Bromhaar, L. C. de Groot, J. H. de Vries, M. Muller, and L. A Afman A saturated fatty acid-rich diet induces an obesity-linked proinflammatory gene expression profile in adipose tissue of subjects at risk of metabolic syndrome Am. J. Clinical Nutrition, December 1, 2009; 90(6): 1656 - 1664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Jiang, H. Zhang, W. Zhang, W. Kong, Y. Zhu, H. Zhang, Q. Xu, Y. Li, and X. Wang Homocysteine promotes vascular smooth muscle cell migration by induction of the adipokine resistin Am J Physiol Cell Physiol, December 1, 2009; 297(6): C1466 - C1476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. C. McGillicuddy, E. H. Chiquoine, C. C. Hinkle, R. J. Kim, R. Shah, H. M. Roche, E. M. Smyth, and M. P. Reilly Interferon {gamma} Attenuates Insulin Signaling, Lipid Storage, and Differentiation in Human Adipocytes via Activation of the JAK/STAT Pathway J. Biol. Chem., November 13, 2009; 284(46): 31936 - 31944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Patsouris, J. G. Neels, W. Fan, P.-P. Li, M. T. A. Nguyen, and J. M. Olefsky Glucocorticoids and Thiazolidinediones Interfere with Adipocyte-mediated Macrophage Chemotaxis and Recruitment J. Biol. Chem., November 6, 2009; 284(45): 31223 - 31235. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Duffaut, A. Zakaroff-Girard, V. Bourlier, P. Decaunes, M. Maumus, P. Chiotasso, C. Sengenes, M. Lafontan, J. Galitzky, and A. Bouloumie Interplay Between Human Adipocytes and T Lymphocytes in Obesity: CCL20 as an Adipochemokine and T Lymphocytes as Lipogenic Modulators Arterioscler Thromb Vasc Biol, October 1, 2009; 29(10): 1608 - 1614. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Shah, Y. Lu, C. C. Hinkle, F. C. McGillicuddy, R. Kim, S. Hannenhalli, T. P. Cappola, S. Heffron, X. Wang, N. N. Mehta, et al. Gene Profiling of Human Adipose Tissue During Evoked Inflammation In Vivo Diabetes, October 1, 2009; 58(10): 2211 - 2219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Mack, R. S. BelAiba, T. Djordjevic, A. Gorlach, H. Hauner, and B. L. Bader Functional analyses reveal the greater potency of preadipocytes compared with adipocytes as endothelial cell activator under normoxia, hypoxia, and TNF{alpha} exposure Am J Physiol Endocrinol Metab, September 1, 2009; 297(3): E735 - E748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wu and C. M. Ballantyne Inflammation, Adipose Tissue, and T Cells: What Is the "Straight Skinny" on Lean Versus Fat Mice? Circ. Res., July 17, 2009; 105(2): e3 - e4. [Full Text] [PDF]
|
|
|
|
|
|
A. Sultan and G. K. Hansson Response to the Letter by Wu and Ballantyne Circ. Res., July 17, 2009; 105(2): e5 - e5. [Full Text] [PDF]
|
|
|
|
|
|
R. Madani, K. Karastergiou, N. C. Ogston, N. Miheisi, R. Bhome, N. Haloob, G. D. Tan, F. Karpe, J. Malone-Lee, M. Hashemi, et al. RANTES release by human adipose tissue in vivo and evidence for depot-specific differences Am J Physiol Endocrinol Metab, June 1, 2009; 296(6): E1262 - E1268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Matter and M. A. S. Stein A Dual Role of CD4+ T Cells in Adipose Tissue? Circ. Res., April 24, 2009; 104(8): 928 - 930. [Full Text] [PDF]
|
|
|
|
|
|
A. Sultan, D. Strodthoff, A.-K. Robertson, G. Paulsson-Berne, J. Fauconnier, P. Parini, M. Ryden, N. Thierry-Mieg, M. E. Johansson, A. V. Chibalin, et al. T Cell-Mediated Inflammation in Adipose Tissue Does Not Cause Insulin Resistance in Hyperlipidemic Mice Circ. Res., April 24, 2009; 104(8): 961 - 968. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bour, S. Caspar-Bauguil, Z. Iffiu-Soltesz, M. Nibbelink, B. Cousin, M. Miiluniemi, M. Salmi, C. Stolen, S. Jalkanen, L. Casteilla, et al. Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein-1 Deficiency Reduces Leukocyte Infiltration into Adipose Tissue and Favors Fat Deposition Am. J. Pathol., March 1, 2009; 174(3): 1075 - 1083. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. T. Robinson and W. R. Taylor Beyond the Adventitia: Exploring the Outer Limits of the Blood Vessel Wall Circ. Res., February 27, 2009; 104(4): 416 - 418. [Full Text] [PDF]
|
|
|
|
|
|
W.-Y. Zhang, E. A. Schwartz, P. A. Permana, and P. D. Reaven Pioglitazone Inhibits the Expression of Inflammatory Cytokines From Both Monocytes and Lymphocytes in Patients With Impaired Glucose Tolerance Arterioscler Thromb Vasc Biol, December 1, 2008; 28(12): 2312 - 2318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Nunemaker, M. Chen, H. Pei, S. D. Kimble, S. R. Keller, J. D. Carter, Z. Yang, K. M. Smith, R. Wu, M. H. Bevard, et al. 12-Lipoxygenase-knockout mice are resistant to inflammatory effects of obesity induced by western diet Am J Physiol Endocrinol Metab, November 1, 2008; 295(5): E1065 - E1075. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Murdolo, C. Herder, Z. Wang, B. Rose, M. Schmelz, and P.-A. Jansson In situ profiling of adipokines in subcutaneous microdialysates from lean and obese individuals Am J Physiol Endocrinol Metab, November 1, 2008; 295(5): E1095 - E1105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. D. Dixit Adipose-immune interactions during obesity and caloric restriction: reciprocal mechanisms regulating immunity and health span J. Leukoc. Biol., October 1, 2008; 84(4): 882 - 892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Z. Rocha, E. J. Folco, G. Sukhova, K. Shimizu, I. Gotsman, A. H. Vernon, and P. Libby Interferon-{gamma}, a Th1 Cytokine, Regulates Fat Inflammation: A Role for Adaptive Immunity in Obesity Circ. Res., August 29, 2008; 103(5): 467 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Huber, F. W. Kiefer, M. Zeyda, B. Ludvik, G. R. Silberhumer, G. Prager, G. J. Zlabinger, and T. M. Stulnig CC Chemokine and CC Chemokine Receptor Profiles in Visceral and Subcutaneous Adipose Tissue Are Altered in Human Obesity J. Clin. Endocrinol. Metab., August 1, 2008; 93(8): 3215 - 3221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Koizumi, T. Kurita-Ochiai, S. Oguchi, and M. Yamamoto Nasal Immunization with Porphyromonas gingivalis Outer Membrane Protein Decreases P. gingivalis-Induced Atherosclerosis and Inflammation in Spontaneously Hyperlipidemic Mice Infect. Immun., July 1, 2008; 76(7): 2958 - 2965. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Kintscher, M. Hartge, K. Hess, A. Foryst-Ludwig, M. Clemenz, M. Wabitsch, P. Fischer-Posovszky, T. F.E. Barth, D. Dragun, T. Skurk, et al. T-lymphocyte Infiltration in Visceral Adipose Tissue: A Primary Event in Adipose Tissue Inflammation and the Development of Obesity-Mediated Insulin Resistance Arterioscler Thromb Vasc Biol, July 1, 2008; 28(7): 1304 - 1310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Herder, T. Illig, J. Baumert, M. Muller, N. Klopp, N. Khuseyinova, C. Meisinger, U. Poschen, S. Martin, W. Koenig, et al. RANTES/CCL5 gene polymorphisms, serum concentrations, and incident type 2 diabetes: results from the MONICA/KORA Augsburg case-cohort study, 1984-2002 Eur. J. Endocrinol., May 1, 2008; 158(5): R1 - R5. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. W. Kiefer, M. Zeyda, J. Todoric, J. Huber, R. Geyeregger, T. Weichhart, O. Aszmann, B. Ludvik, G. R. Silberhumer, G. Prager, et al. Osteopontin Expression in Human and Murine Obesity: Extensive Local Up-Regulation in Adipose Tissue but Minimal Systemic Alterations Endocrinology, March 1, 2008; 149(3): 1350 - 1357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. Ohman, Y. Shen, C. I. Obimba, A. P. Wright, M. Warnock, D. A. Lawrence, and D. T. Eitzman Visceral Adipose Tissue Inflammation Accelerates Atherosclerosis in Apolipoprotein E-Deficient Mice Circulation, February 12, 2008; 117(6): 798 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Strissel, Z. Stancheva, H. Miyoshi, J. W. Perfield II, J. DeFuria, Z. Jick, A. S. Greenberg, and M. S. Obin Adipocyte Death, Adipose Tissue Remodeling, and Obesity Complications Diabetes, December 1, 2007; 56(12): 2910 - 2918. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C W. Smith Diet and leukocytes Am. J. Clinical Nutrition, November 1, 2007; 86(5): 1257 - 1258. [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Guzik, N. E. Hoch, K. A. Brown, L. A. McCann, A. Rahman, S. Dikalov, J. Goronzy, C. Weyand, and D. G. Harrison Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction J. Exp. Med., October 1, 2007; 204(10): 2449 - 2460. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Maury, K. Ehala-Aleksejev, Y. Guiot, R. Detry, A. Vandenhooft, and S. M. Brichard Adipokines oversecreted by omental adipose tissue in human obesity Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E656 - E665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Matter and C. Handschin RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted), Inflammation, Obesity, and the Metabolic Syndrome Circulation, February 27, 2007; 115(8): 946 - 948. [Full Text] [PDF]
|
|