Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Outros Autores: | , , , , , , , , , , , |
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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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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1814268463358672896 |