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TNF-alpha acts in the hypothalamus inhibiting food intake and increasing the respiratory quotient--effects on leptin and insulin signaling pathways.
Romanatto, Talita; Cesquini, Maristela; Amaral, Maria E; Roman, Erika A; Moraes, Juliana C; Torsoni, Márcio A; Cruz-Neto, Ariovaldo P; Velloso, Lício A.
Afiliação
  • Romanatto T; Department of Internal Medicine, State University of Campinas, Brazil.
Peptides ; 28(5): 1050-8, 2007 May.
Article em En | MEDLINE | ID: mdl-17459524
Acting in the hypothalamus, tumor necrosis factor-alpha (TNF-alpha) produces a potent anorexigenic effect. However, the molecular mechanisms involved in this phenomenon are poorly characterized. In this study, we investigate the capacity of TNF-alpha to activate signal transduction in the hypothalamus through elements of the pathways employed by the anorexigenic hormones insulin and leptin. High dose TNF-alpha promotes a reduction of 25% in 12h food intake, which is an inhibitory effect that is marginally inferior to that produced by insulin and leptin. In addition, high dose TNF-alpha increases body temperature and respiratory quotient, effects not reproduced by insulin or leptin. TNF-alpha, predominantly at the high dose, is also capable of activating canonical pro-inflammatory signal transduction in the hypothalamus, inducing JNK, p38, and NFkappaB, which results in the transcription of early responsive genes and expression of proteins of the SOCS family. Also, TNF-alpha activates signal transduction through JAK-2 and STAT-3, but does not activate signal transduction through early and intermediary elements of the insulin/leptin signaling pathways such as IRS-2, Akt, ERK and FOXO1. When co-injected with insulin or leptin, TNF-alpha, at both high and low doses, partially impairs signal transduction through IRS-2, Akt, ERK and FOXO1 but not through JAK-2 and STAT-3. This effect is accompanied by the partial inhibition of the anorexigenic effects of insulin and leptin, when the low, but not the high dose of TNF-alpha is employed. In conclusion, TNF-alpha, on a dose-dependent way, modulates insulin and leptin signaling and action in the hypothalamus.
Assuntos
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Base de dados: MEDLINE Assunto principal: Fator de Necrose Tumoral alfa / Respiração Celular / Leptina / Ingestão de Alimentos / Hipotálamo / Insulina Limite: Animals Idioma: En Ano de publicação: 2007 Tipo de documento: Article
Buscar no Google
Base de dados: MEDLINE Assunto principal: Fator de Necrose Tumoral alfa / Respiração Celular / Leptina / Ingestão de Alimentos / Hipotálamo / Insulina Limite: Animals Idioma: En Ano de publicação: 2007 Tipo de documento: Article