Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats

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dc.contributor.authorRopelle, Eduardo Rochete
dc.contributor.authorPauli, José Rodrigo [UNIFESP]
dc.contributor.authorPrada, Patrícia de Oliveira
dc.contributor.authorCintra, Dennys Esper
dc.contributor.authorRocha, Guilherme Zweig
dc.contributor.authorMoraes, Juliana Contin
dc.contributor.authorFrederico, Marisa Jadna Silva
dc.contributor.authorLuz, Gabrielle da
dc.contributor.authorPinho, Ricardo Aurino de
dc.contributor.authorCarvalheira, José Barreto Campello
dc.contributor.authorVelloso, Licio Augusto
dc.contributor.authorSaad, Mario Jose Abdalla
dc.contributor.authorSouza, Claudio Teodoro de
dc.contributor.institutionUniv Extremo Catarinense
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T13:52:32Z
dc.date.available2016-01-24T13:52:32Z
dc.date.issued2009-05-15
dc.description.abstractInsulin signalling in the hypothalamus plays a role in maintaining body weight. the forkhead transcription factor Foxo1 is an important mediator of insulin signalling in the hypothalamus. Foxo1 stimulates the transcription of the orexigenic neuropeptide Y and Agouti-related protein through the phosphatidylinositol-3-kinase/Akt signalling pathway, but the role of hypothalamic Foxo1 in insulin resistance and obesity remains unclear. Here, we identify that a high-fat diet impaired insulin-induced hypothalamic Foxo1 phosphorylation and degradation, increasing the nuclear Foxo1 activity and hyperphagic response in rats. Thus, we investigated the effects of the intracerebroventricular (i.c.v.) microinfusion of Foxo1-antisense oligonucleotide (Foxo1-ASO) and evaluated the food consumption and weight gain in normal and diet-induced obese (DIO) rats. Three days of Foxo1-ASO microinfusion reduced the hypothalamic Foxo1 expression by about 85%. i.c.v. infusion of Foxo1-ASO reduced the cumulative food intake (21%), body weight change (28%), epididymal fat pad weight (22%) and fasting serum insulin levels (19%) and increased the insulin sensitivity (34%) in DIO but not in control animals. Collectively, these data showed that the Foxo1-ASO treatment blocked the orexigenic effects of Foxo1 and prevented the hyperphagic response in obese rats. Thus, pharmacological manipulation of Foxo1 may be used to prevent or treat obesity.en
dc.description.affiliationUniv Extremo Catarinense, PPGCS, Programa Posgrad Ciencias Saude, BR-88806000 Criciuma, SC, Brazil
dc.description.affiliationUniv Estadual Campinas, FCM, Dept Clin Med, Campinas, SP, Brazil
dc.description.affiliationUNIFESP, Dept Biociencias, Curso Educ Fis Modalidade Saude, Santos, SP, Brazil
dc.description.affiliationUnifespUNIFESP, Dept Biociencias, Curso Educ Fis Modalidade Saude, Santos, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt
dc.format.extent2341-2351
dc.identifierhttps://dx.doi.org/10.1113/jphysiol.2009.170050
dc.identifier.citationJournal of Physiology-london. Malden: Wiley-Blackwell Publishing, Inc, v. 587, n. 10, p. 2341-2351, 2009.
dc.identifier.doi10.1113/jphysiol.2009.170050
dc.identifier.issn0022-3751
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/31520
dc.identifier.wosWOS:000266491300020
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofJournal of Physiology-london
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.titleInhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity ratsen
dc.typeinfo:eu-repo/semantics/article
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