Fsp27/CIDEC is a CREB target gene induced during fasting and regulated by fatty acid oxidation rate

Detalhes bibliográficos
Autor(a) principal: Gonçalves, Joana Fernandes
Data de Publicação: 2012
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/8198
Resumo: Dissertação para obtenção do Grau de Mestre em Biotecnologia
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spelling Fsp27/CIDEC is a CREB target gene induced during fasting and regulated by fatty acid oxidation rateCIDEC/Fsp27FastingFAOCREBSIRT1Amino-acid deprivationDissertação para obtenção do Grau de Mestre em BiotecnologiaFsp27 (CIDEC the human homologue) is a lipid droplet protein that when overexpressed down regulates fatty acid oxidation (FAO). Previous results of this group showed that Fsp27/CIDEC expression is regulated by fasting in liver in a time-dependent manner. The present study aimed to elucidate the mechanism by which Fsp27/CIDEC is mediating fasting adaptation and regulated by FAO rate in liver. We showed that induction of Fsp27/CIDEC expression during fasting is not regulated by PPARα. Pharmacological inhibition of FAO by etomoxir induces Fsp27/CIDEC in fasting conditions and this regulation is not mediated by PPAR – a master regulator in triglyceride accumulation. The early response to fasting can be explained by a canonical PKA-CREB-CRTC2 signaling pathway, since CIDEC expression was increased by forskolin which effect was lost when a vector containing a dominant negative of CREB construct(KCREB) was co-transfected in HepG2 cells, and, consistently, Fsp27 promoter activity was increased by CREB. Also, CIDEC expression was up-regulated by specific Sirt1 depletion by siRNA in HepG2 cells. Our data demonstrate that Fsp27/CIDEC is a CREB target gene that could be up-regulated when FAO is reduced and that fluctuations in SIRT1 activity, in response to nutrient availability, mediate this mechanism. The peroxissome proliferator-activated receptor gamma coactivator-1α (PGC-1α) induces and coordinates gene expression that stimulates metabolic pathways linked to the fasted response in liver including gluconeogenesis. We observed that Pgc-1α expression was increased in late fasting in the liver of mice previously subjected to a leucin deprived diet. These conditions also enhanced transcription from Foxa2 gene. This study showed that the mechanism regulating the induction of Pgc-1α expression under these conditions is not mediated by the recruitment of CREB by Foxa2 to the Pgc-1α or the Pepck promoters, since both promoters activities were not enhanced by the co-transfection of FOXA2 with CREB in HepG2 cells.Faculdade de Ciências e TecnologiaHaro Bustista, DiegoMarrero González, PedroRUNGonçalves, Joana Fernandes2012-11-23T12:14:50Z20122012-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10362/8198enginfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T03:40:42Zoai:run.unl.pt:10362/8198Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:18:00.706892Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Fsp27/CIDEC is a CREB target gene induced during fasting and regulated by fatty acid oxidation rate
title Fsp27/CIDEC is a CREB target gene induced during fasting and regulated by fatty acid oxidation rate
spellingShingle Fsp27/CIDEC is a CREB target gene induced during fasting and regulated by fatty acid oxidation rate
Gonçalves, Joana Fernandes
CIDEC/Fsp27
Fasting
FAO
CREB
SIRT1
Amino-acid deprivation
title_short Fsp27/CIDEC is a CREB target gene induced during fasting and regulated by fatty acid oxidation rate
title_full Fsp27/CIDEC is a CREB target gene induced during fasting and regulated by fatty acid oxidation rate
title_fullStr Fsp27/CIDEC is a CREB target gene induced during fasting and regulated by fatty acid oxidation rate
title_full_unstemmed Fsp27/CIDEC is a CREB target gene induced during fasting and regulated by fatty acid oxidation rate
title_sort Fsp27/CIDEC is a CREB target gene induced during fasting and regulated by fatty acid oxidation rate
author Gonçalves, Joana Fernandes
author_facet Gonçalves, Joana Fernandes
author_role author
dc.contributor.none.fl_str_mv Haro Bustista, Diego
Marrero González, Pedro
RUN
dc.contributor.author.fl_str_mv Gonçalves, Joana Fernandes
dc.subject.por.fl_str_mv CIDEC/Fsp27
Fasting
FAO
CREB
SIRT1
Amino-acid deprivation
topic CIDEC/Fsp27
Fasting
FAO
CREB
SIRT1
Amino-acid deprivation
description Dissertação para obtenção do Grau de Mestre em Biotecnologia
publishDate 2012
dc.date.none.fl_str_mv 2012-11-23T12:14:50Z
2012
2012-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/8198
url http://hdl.handle.net/10362/8198
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Faculdade de Ciências e Tecnologia
publisher.none.fl_str_mv Faculdade de Ciências e Tecnologia
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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