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(Circulation Research. 2009;104:961.)
© 2009 American Heart Association, Inc.

Molecular Medicine

T Cell–Mediated Inflammation in Adipose Tissue Does Not Cause Insulin Resistance in Hyperlipidemic Mice

Ariane Sultan, Daniela Strodthoff, Anna-Karin Robertson, Gabrielle Paulsson-Berne, Jeremy Fauconnier, Paolo Parini, Mikael Rydén, Nicolas Thierry-Mieg, Maria E. Johansson, Alexander V. Chibalin, Juleen R. Zierath, Peter Arner, Göran K. Hansson

From the Center for Molecular Medicine and Department of Medicine (A.S., D.S., A.-K.R., G.P.B., M.E.J., G.K.H.), Karolinska University Hospital, Stockholm, Sweden; Institut National de la Santé et de la Recherche Médicale (A.S.), ERI 25 and Université de Montpellier 1, Unité de Formation et de Recherche, Médecine, Montpellier, France; Departments of Physiology and Pharmacology (J.F.) and Molecular Medicine and Surgery (A.V.C., J.R.Z.), Karolinska Institutet, Stockholm, Sweden; Departments Laboratory Medicine (P.P.) and Medicine (M.R., P.A.), Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden; and Laboratoire Techniques de l’Ingénierie Médicale et de la Complexité–Informatique, Mathématiques et Applications de Grenoble (N.T.-M.), Faculte de Medecine, La Tronche, France.

Correspondence to Dr Goran K. Hansson, Center for Molecular Medicine L8:03, Karolinska University Hospital, SE-17176 Stockholm, Sweden. E-mail Goran.Hansson{at}ki.se

Obesity is associated with chronic inflammation in adipose tissue. Proinflammatory cytokines including tumor necrosis factor- and interleukin-6 secreted by adipose tissue during the metabolic syndrome are proposed to cause local and general insulin resistance and promote development of type 2 diabetes. We have used a compound mutant mouse, Apoe^–/–xCD4dnTGFbR, with dysregulation of T-cell activation, excessive production of proinflammatory cytokines, hyperlipidemia, and atherosclerosis, to dissect the role of inflammation in adipose tissue metabolism. These mice are lean, which avoids confounding effects of concomitant obesity. Expression and secretion of a set of proinflammatory factors including tumor necrosis factor-, interferon-, and monocyte chemoattractant protein-1 was increased in adipose tissue of Apoe^–/–xCD4dnTGFbR mice, as was the enzyme 11β-hydroxysteroid dehydrogenase type 1, which converts cortisone to bioactive cortisol. Interleukin-6, which has an inhibitory glucocorticoid response element in its promoter, was not upregulated. In spite of intense local inflammation, insulin sensitivity was not impaired in adipose tissue of Apoe^–/–xCD4dnTGFbR mice unless exogenous interleukin-6 was administered. In conclusion, T-cell activation causes inflammation in adipose tissue but does not lead to insulin resistance in this tissue in the absence of interleukin-6.

Key Words: adipose tissue • cytokines • inflammation • insulin resistance • interleukin-6 • T cells

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