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


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 IFNgamma, 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.
Kintscher
Ulrich
U
Department of Internal Medicine II-Cardiology, University of Ulm, Robert-Koch-Str 8, D-89081 Ulm, Germany.
Hartge
Martin
M
Hess
Katharina
K
Foryst-Ludwig
Anna
A
Clemenz
Markus
M
Wabitsch
Martin
M
Fischer-Posovszky
Pamela
P
Barth
Thomas F E
TF
Dragun
Duska
D
Skurk
Thomas
T
Hauner
Hans
H
Blüher
Matthias
M
Unger
Thomas
T
Wolf
Anna-Maria
AM
Knippschild
Uwe
U
Hombach
Vinzenz
V
Marx
Nikolaus
N
D017667:Adipocytes / Q000276:immunology; D000368:Aged; D000818:Animals; D049628:Body Size; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000503:physiopathology; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D006801:Humans; D007333:Insulin Resistance / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009765:Obesity / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D015434:Panniculitis / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D013997:Time Factors
C111835:CCL2 protein, human; C515255:CXCL12 protein, human; D018932:Chemokine CCL2; D054377:Chemokine CXCL12; D004041:Dietary Fats; D007371:Interferon-gamma