RESUMO
BACKGROUND: Tumor necrosis factor (TNF)-α, which is released as a soluble form by ectodomain shedding of TNF-α converting enzyme (Tace), is known to play a pivotal role in obesity-induced insulin resistance. The role of Tace in obesity-induced metabolic disorders was to be clarified in this study. METHODS AND RESULTS: Transgenic mice with temporal systemic Tace deletion (TaceMx1) and their non-transgenic littermates (CON) were fed a standard diet or a high-fat diet (HFD) from 6 weeks of age. The increased body, liver and epididymal adipose tissue (EAT) weights, systolic blood pressure, and fasting glucose and lipid levels and decreased serum adiponectin level 12 weeks after starting a HFD were suppressed by Tace inactivation. A HFD/TaceMx1 showed ameliorated glucose tolerance and insulin sensitivity compared with HFD/CON. Indirect calorimetry showed that energy expenditure and oxidation of both fat and carbohydrate were higher in HFD/TaceMx1 than HFD/CON. Marked hepatosteatosis, increased triglyceride content and TNF-α expression in liver, and increased adipocyte size, macrophage infiltration and TNF-α and monocyte chemoattractant protein-1 expression in EAT induced by a HFD were attenuated in HFD/TaceMx1. CONCLUSIONS: Inactivation of Tace suppressed HFD-induced obesity, insulin resistance, hepatosteatosis and adipose tissue remodeling in association with increased energy expenditure, suggesting an important role of Tace in the development of obesity-induced metabolic disorders.
Assuntos
Proteínas ADAM/fisiologia , Gorduras na Dieta/farmacologia , Metabolismo Energético/genética , Homeostase/genética , Resistência à Insulina , Proteínas ADAM/deficiência , Proteínas ADAM/genética , Proteína ADAM17 , Tecido Adiposo , Animais , Fígado Gorduroso/etiologia , Deleção de Genes , Camundongos , Camundongos Transgênicos , Obesidade , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Intravascular large B-cell lymphoma (IVL) is a rare subtype of B-cell lymphoma presenting with neurological and dermatological lesions in addition to generalized symptoms such as fever and malaise. It may also be associated with variable manifestations of affected organs due to extranodal progression predominantly in the lumen of the small vessels. Here, we report a case of IVL with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) as the sole manifestation at the initial presentation. The present case suggests that hormonal disturbances may progress in advance in IVL, before generalized symptoms develop.