title: Reduction of hypothalamic protein tyrosine phosphatase improves insulin and leptin resistance in diet-induced obese rats.
abstract: 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 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 diabetes-induced obese rats.
authors.affiliation: Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.
authors.forename: Paty Karoll
authors.initials: PK
authors.lastname: Picardi
authors.forename: Vivian Cristine
authors.initials: VC
authors.lastname: Calegari
authors.forename: Patricia Oliveira
authors.initials: PO
authors.lastname: Prada
authors.forename: Patrícia de Oliveira
authors.initials: Pde O
authors.lastname: Prada
authors.forename: Juliana Contin
authors.initials: JC
authors.lastname: Moraes
authors.forename: Eliana
authors.initials: E
authors.lastname: Araújo
authors.forename: Maria Cristina Cintra Gomes
authors.initials: MC
authors.lastname: Marcondes
authors.forename: Miriam
authors.initials: M
authors.lastname: Ueno
authors.forename: José Barreto Campello
authors.initials: JB
authors.lastname: Carvalheira
authors.forename: Licio Augusto
authors.initials: LA
authors.lastname: Velloso
authors.forename: Mario José Abdalla
authors.initials: MJ
authors.lastname: Saad
mesh_terms: D050154:Adiposity / Q000187:drug effects / Q000235:genetics; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D004036:Diet, Atherogenic; D004351:Drug Resistance / Q000187:drug effects* / Q000235:genetics; D004435:Eating / Q000187:drug effects / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007276:Injections, Intraventricular; D007328:Insulin / Q000494:pharmacology*; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012527:Satiation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007328:Insulin; D020738:Leptin; D016376:Oligonucleotides, Antisense; D017027:Protein Tyrosine Phosphatases; D005947:Glucose