Reduction hypothalamic of PTP-1B improves the sensibility to the insulin and leptin in normal and obese rats / Redução hipotalamica da PTP-1B melhora a sensibilidade a insulina e leptina em ratos normais e obesos

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

Protein tyrosine phosphatase (PTP1B) has been implicated in the negative regulation of insulin and leptin signaling. PTP1B knockout mice are hypersensitive to insulin and leptin and resistant to obesity when fed a high-fat diet. We investigated the role of hypothalamic PTP1B in the regulation of food intake, insulin and leptin actions and signaling in rats through selective decreases in PTP1B expression in discrete hypothalamic nuclei. We generated a selective, transient reduction in PTP1B by infusion of an antisense oligonucleotide designed to blunt the expression of PTP1B in rat hypothalamic areas surrounding the third ventricle, in control and obese rats. The selective decrease in hypothalamic PTP1B resulted in decreased food intake, reduced body weight, reduced adiposity and reduced leptin levels after high-fat feeding, improved leptin and insulin action and signaling in hypothalamus and also in insulin action in liver and muscle. Our results show that hypothalamic PTP1B reduction should be sufficient to promote appreciable weight reduction and improve insulin and leptin sensitivity and signaling and glucose homeostasis in DIO rats

ASSUNTO(S)

leptin protein tyrosine phosphatase insulin proteina tirosina fosfatase leptina insulina

ACESSO AO ARTIGO

Documentos Relacionados