Abstract
Obesity is associated with chronic inflammation in adipose tissue. Proinflammatory cytokines including tumor necrosis factor-alpha 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-alpha, interferon-gamma, and monocyte chemoattractant protein-1 was increased in adipose tissue of Apoe(-/-)xCD4dnTGFbR mice, as was the enzyme 11beta-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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
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Adipokines / metabolism
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Adipose Tissue, White / immunology*
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Adipose Tissue, White / physiopathology
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Animals
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Apolipoproteins E / deficiency
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Apolipoproteins E / genetics
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Atherosclerosis / genetics
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Atherosclerosis / immunology*
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Atherosclerosis / physiopathology
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Blood Glucose / metabolism
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Body Weight
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CD4 Antigens / genetics
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CD4-Positive T-Lymphocytes / immunology*
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Chemokine CCL2 / metabolism
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Disease Models, Animal
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Female
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Gene Expression Profiling
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Hydrocortisone / metabolism
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Hyperlipidemias / genetics
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Hyperlipidemias / immunology*
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Hyperlipidemias / physiopathology
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Inflammation / genetics
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Inflammation / immunology*
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Inflammation / physiopathology
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Inflammation Mediators / metabolism
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Insulin Resistance*
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Interferon-gamma / metabolism
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Interleukin-6 / metabolism
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Lipogenesis
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Promoter Regions, Genetic
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Protein Serine-Threonine Kinases / genetics
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Receptor, Transforming Growth Factor-beta Type II
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Receptors, Transforming Growth Factor beta / genetics
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Time Factors
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Adipokines
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Apolipoproteins E
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Blood Glucose
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CD4 Antigens
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Ccl2 protein, mouse
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Chemokine CCL2
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Inflammation Mediators
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Interleukin-6
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Receptors, Transforming Growth Factor beta
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Tumor Necrosis Factor-alpha
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Interferon-gamma
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11-beta-Hydroxysteroid Dehydrogenase Type 1
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Protein Serine-Threonine Kinases
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Receptor, Transforming Growth Factor-beta Type II
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Hydrocortisone