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

Detalhes bibliográficos
Autor(a) principal: Ropelle, Eduardo Rochete
Data de Publicação: 2009
Outros Autores: Pauli, José Rodrigo [UNIFESP], Prada, Patrícia de Oliveira, Cintra, Dennys Esper, Rocha, Guilherme Zweig, Moraes, Juliana Contin, Frederico, Marisa Jadna Silva, Luz, Gabrielle da, Pinho, Ricardo Aurino de, Carvalheira, José Barreto Campello, Velloso, Licio Augusto, Saad, Mario Jose Abdalla, Souza, Claudio Teodoro de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: https://dx.doi.org/10.1113/jphysiol.2009.170050
https://repositorio.unifesp.br/handle/11600/31520
Resumo: Insulin 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.
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spelling Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity ratsInsulin 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.Univ Extremo Catarinense, PPGCS, Programa Posgrad Ciencias Saude, BR-88806000 Criciuma, SC, BrazilUniv Estadual Campinas, FCM, Dept Clin Med, Campinas, SP, BrazilUNIFESP, Dept Biociencias, Curso Educ Fis Modalidade Saude, Santos, SP, BrazilUNIFESP, Dept Biociencias, Curso Educ Fis Modalidade Saude, Santos, SP, BrazilWeb of ScienceFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Wiley-BlackwellUniv Extremo CatarinenseUniversidade Estadual de Campinas (UNICAMP)Universidade Federal de São Paulo (UNIFESP)Ropelle, Eduardo RochetePauli, José Rodrigo [UNIFESP]Prada, Patrícia de OliveiraCintra, Dennys EsperRocha, Guilherme ZweigMoraes, Juliana ContinFrederico, Marisa Jadna SilvaLuz, Gabrielle daPinho, Ricardo Aurino deCarvalheira, José Barreto CampelloVelloso, Licio AugustoSaad, Mario Jose AbdallaSouza, Claudio Teodoro de2016-01-24T13:52:32Z2016-01-24T13:52:32Z2009-05-15info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion2341-2351https://dx.doi.org/10.1113/jphysiol.2009.170050Journal of Physiology-london. Malden: Wiley-Blackwell Publishing, Inc, v. 587, n. 10, p. 2341-2351, 2009.10.1113/jphysiol.2009.1700500022-3751https://repositorio.unifesp.br/handle/11600/31520WOS:000266491300020engJournal of Physiology-londoninfo:eu-repo/semantics/openAccesshttp://olabout.wiley.com/WileyCDA/Section/id-406071.htmlreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2021-12-14T20:20:41Zoai:repositorio.unifesp.br/:11600/31520Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652021-12-14T20:20:41Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats
title Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats
spellingShingle Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats
Ropelle, Eduardo Rochete
title_short Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats
title_full Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats
title_fullStr Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats
title_full_unstemmed Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats
title_sort Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats
author Ropelle, Eduardo Rochete
author_facet Ropelle, Eduardo Rochete
Pauli, José Rodrigo [UNIFESP]
Prada, Patrícia de Oliveira
Cintra, Dennys Esper
Rocha, Guilherme Zweig
Moraes, Juliana Contin
Frederico, Marisa Jadna Silva
Luz, Gabrielle da
Pinho, Ricardo Aurino de
Carvalheira, José Barreto Campello
Velloso, Licio Augusto
Saad, Mario Jose Abdalla
Souza, Claudio Teodoro de
author_role author
author2 Pauli, José Rodrigo [UNIFESP]
Prada, Patrícia de Oliveira
Cintra, Dennys Esper
Rocha, Guilherme Zweig
Moraes, Juliana Contin
Frederico, Marisa Jadna Silva
Luz, Gabrielle da
Pinho, Ricardo Aurino de
Carvalheira, José Barreto Campello
Velloso, Licio Augusto
Saad, Mario Jose Abdalla
Souza, Claudio Teodoro de
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Univ Extremo Catarinense
Universidade Estadual de Campinas (UNICAMP)
Universidade Federal de São Paulo (UNIFESP)
dc.contributor.author.fl_str_mv Ropelle, Eduardo Rochete
Pauli, José Rodrigo [UNIFESP]
Prada, Patrícia de Oliveira
Cintra, Dennys Esper
Rocha, Guilherme Zweig
Moraes, Juliana Contin
Frederico, Marisa Jadna Silva
Luz, Gabrielle da
Pinho, Ricardo Aurino de
Carvalheira, José Barreto Campello
Velloso, Licio Augusto
Saad, Mario Jose Abdalla
Souza, Claudio Teodoro de
description Insulin 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.
publishDate 2009
dc.date.none.fl_str_mv 2009-05-15
2016-01-24T13:52:32Z
2016-01-24T13:52:32Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://dx.doi.org/10.1113/jphysiol.2009.170050
Journal of Physiology-london. Malden: Wiley-Blackwell Publishing, Inc, v. 587, n. 10, p. 2341-2351, 2009.
10.1113/jphysiol.2009.170050
0022-3751
https://repositorio.unifesp.br/handle/11600/31520
WOS:000266491300020
url https://dx.doi.org/10.1113/jphysiol.2009.170050
https://repositorio.unifesp.br/handle/11600/31520
identifier_str_mv Journal of Physiology-london. Malden: Wiley-Blackwell Publishing, Inc, v. 587, n. 10, p. 2341-2351, 2009.
10.1113/jphysiol.2009.170050
0022-3751
WOS:000266491300020
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal of Physiology-london
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
http://olabout.wiley.com/WileyCDA/Section/id-406071.html
eu_rights_str_mv openAccess
rights_invalid_str_mv http://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.format.none.fl_str_mv 2341-2351
dc.publisher.none.fl_str_mv Wiley-Blackwell
publisher.none.fl_str_mv Wiley-Blackwell
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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