T cell-mediated inflammation in adipose tissue does not cause insulin resistance in hyperlipidemic mice

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Nyckelord

11-beta-Hydroxysteroid Dehydrogenase Type 1/metabolism

Adipokines/metabolism

Adipose Tissue

White/*immunology/physiopathology

Animals

Antigens

CD4/genetics

Apolipoproteins E/deficiency/genetics

Atherosclerosis/genetics/*immunology/physiopathology

Blood Glucose/metabolism

Body Weight

CD4-Positive T-Lymphocytes/*immunology

Chemokine CCL2/metabolism

Disease Models

Animal

Female

Gene Expression Profiling

Hydrocortisone/metabolism

Hyperlipidemias/genetics/*immunology/physiopathology

Inflammation/genetics/*immunology/physiopathology

Inflammation Mediators/metabolism

*Insulin Resistance

Interferon-gamma/metabolism

Interleukin-6/metabolism

Lipogenesis

Mice

Mice

Inbred C57BL

Mice

Knockout

Mice

Transgenic

Promoter Regions

Genetic

Protein-Serine-Threonine Kinases/genetics

Receptors

Transforming Growth Factor beta/genetics

Time Factors

Tumor Necrosis Factor-alpha/metabolism

Publikations- och innehållstyp

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