T-lymphocyte infiltration in visceral adipose tissue -: A primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance

被引:554
作者
Kintscher, Ulrich [2 ]
Hartge, Martin [2 ]
Hess, Katharina [1 ]
Foryst-Ludwig, Anna [2 ]
Clemenz, Markus [2 ]
Wabitsch, Martin [3 ]
Fischer-Posovszky, Pamela [3 ]
Barth, Thomas F. E. [4 ]
Dragun, Duska [5 ]
Skurk, Thomas [6 ]
Hauner, Hans [6 ]
Blueher, Matthias [7 ]
Unger, Thomas [2 ]
Wolf, Anna-Maria [8 ]
Knippschild, Uwe [8 ]
Hombach, Vinzenz [1 ]
Marx, Nikolaus [1 ]
机构
[1] Univ Ulm, Dept Internal Med 2 Cardiol, D-89081 Ulm, Germany
[2] Charite Univ Med Berlin, Inst Pharmacol, Cardiovasc Res Ctr, D-13353 Berlin, Germany
[3] Univ Ulm, Dept Pediat & Adolescent Med, Div Pediat Endocrinol, D-89081 Ulm, Germany
[4] Univ Ulm, Dept Pathol, D-89081 Ulm, Germany
[5] Charite Univ Med Berlin, Campus Virchow Clin, Dept Nephrol, D-13353 Berlin, Germany
[6] Tech Univ Munich, Else Kroner Fresenius Ctr Nutr Med, D-8000 Munich, Germany
[7] Univ Leipzig, Dept Med, Leipzig, Germany
[8] Univ Ulm, Dept Gen Visceral & Transplantat Surg, D-89081 Ulm, Germany
关键词
inflammation; insulin resistance; monocytes; lymphocytes;
D O I
10.1161/ATVBAHA.108.165100
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Adipose tissue inflammation may play a critical role in the pathogenesis of insulin resistance (IR). The present study examined the role of lymphocytes in adipose tissue inflammation and IR. Methods and Results-In a mouse model of obesity-mediated IR, high-fat diet (HFD) induced IR already after 5 weeks, which was associated with a marked T-lymphocyte infiltration in visceral adipose tissue. In contrast, recruitment of macrophages was delayed with an increase of MAC3-positive staining and F4/80 mRNA expression after 10 weeks of HFD, suggesting a dissociation of macrophage invasion into adipose tissue and IR initiation. In patients with type 2 diabetes, lymphocyte content in adipose tissue biopsies significantly correlated with waist circumference, a marker of IR. Immunohistochemical staining of human adipose tissue revealed the presence of mainly CD4-positive lymphocytes as well as macrophage infiltration. Most macrophages were HLA-DR-positive, reflecting activation through IFN gamma, a cytokine released from CD4-positive lymphocytes. Conclusions-Proinflammatory T-lymphocytes are present in visceral adipose tissue and may contribute to local inflammatory cell activation before the appearance of macrophages, suggesting that these cells could play an important role in the initiation and perpetuation of adipose tissue inflammation as well as the development of IR.
引用
收藏
页码:1304 / 1310
页数:7
相关论文
共 21 条
  • [21] Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance
    Xu, HY
    Barnes, GT
    Yang, Q
    Tan, Q
    Yang, DS
    Chou, CJ
    Sole, J
    Nichols, A
    Ross, JS
    Tartaglia, LA
    Chen, H
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2003, 112 (12) : 1821 - 1830