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

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Abstract
Obesity is associated with chronic inflammation in adipose tissue. Proinflammatory cytokines including tumor necrosis factor-α 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−/−×CD4dnTGFbR, 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-α, interferon-γ, and monocyte chemoattractant protein-1 was increased in adipose tissue of Apoe−/−×CD4dnTGFbR mice, as was the enzyme 11β-hydroxysteroid dehydrogenase type 1, which converts cortisone to bioactive cortisol. Interleukin-6, which has an inhibitory glucocorticoid response eleme...