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This version published online on May 8, 2008
Endocrinology, doi:10.1210/en.2007-1506
A more recent version of this article appeared on August 1, 2008
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Submitted on November 6, 2007
Accepted on April 25, 2008

Reduction of hypothalamic PTP1B improves insulin and leptin resistance in diet-induced obese rats

Paty Karoll Picardi, Vivian Cristine Calegari, Patrícia de Oliveira Prada, Juliana Contin Moraes, Eliana Araújo, Maria Cristina Cintra Gomes Marcondes, Miriam Ueno, José Barreto Campello Carvalheira, Licio Augusto Velloso, and Mario José Abdalla Saad*

Departamento de Clínica Médica, FCM, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil

* To whom correspondence should be addressed. E-mail: msaad{at}fcm.unicamp.com.br.

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 signalling 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 after high-fat feeding, improved leptin and insulin action and signaling in hypothalamus and may also have a role in the improvement in glucose metabolism in DIO rats.
Key words: PTP1B • obesity • insulin action • leptin action • insulin signaling






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