Published online before print April 17, 2008, doi: 10.1161/ATVBAHA.108.165100
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© 2008 American Heart Association, Inc.
Integrative Physiology/Experimental Medicine |
T-lymphocyte Infiltration in Visceral Adipose Tissue
A Primary Event in Adipose Tissue Inflammation and the Development of Obesity-Mediated Insulin Resistance
From the Center for Cardiovascular Research (U.K., M.H., A.F.-L., M.C., T.U.), Institute of Pharmacology, Charité-Universitaetsmedizin, Berlin, Germany; the Department of Internal Medicine II – Cardiology (K.H., V.H., N.M.), University of Ulm, Germany; the Division of Pediatric Endocrinology, Department of Pediatrics and Adolescent Medicine (M.W., P.F.-P.), University of Ulm, Germany; the Department of Pathology (T.F.E.B.), University of Ulm, Germany; the Department of Nephrology, Campus Virchow Clinic and Center for Cardiovascular Research (D.D.), Charité-Universitaetsmedizin Berlin, Germany; Else Kröner-Fresenius-Centre for Nutritional Medicine (T.S., H.H.), Technische Universität München, Germany; the Department of Medicine (M.B.), University of Leipzig, Germany; and the Department of General, Visceral, and Transplantation Surgery (A.-M.W., U.K.), University of Ulm, Germany.
Correspondence to Nikolaus Marx, MD, Department of Internal Medicine II – Cardiology, University of Ulm, Robert-Koch-Str 8, D-89081 Ulm, Germany. E-mail nikolaus.marx{at}uniklinik-ulm.de
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
, 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.
In a mouse model of insulin resistance (IR), high-fat diet induced IR after 5 weeks, which was associated with a marked proinflammatory T-lymphocyte infiltration in visceral adipose tissue, whereas macrophage recruitment was delayed after 10 weeks of diet, suggesting a dissociation of macrophage invasion into adipose tissue and IR initiation.
Key Words: inflammation • insulin resistance • monocytes • lymphocytes
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