Publicação
Fsp27/CIDEC is a CREB target gene induced during fasting and regulated by fatty acid oxidation rate
| dc.contributor.advisor | Haro Bustista, Diego | |
| dc.contributor.advisor | Marrero González, Pedro | |
| dc.contributor.author | Gonçalves, Joana Fernandes | |
| dc.date.accessioned | 2012-11-23T12:14:50Z | |
| dc.date.available | 2012-11-23T12:14:50Z | |
| dc.date.issued | 2012 | |
| dc.description | Dissertação para obtenção do Grau de Mestre em Biotecnologia | por |
| dc.description.abstract | Fsp27 (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. | por |
| dc.identifier.uri | http://hdl.handle.net/10362/8198 | |
| dc.language.iso | eng | por |
| dc.publisher | Faculdade de Ciências e Tecnologia | por |
| dc.subject | CIDEC/Fsp27 | por |
| dc.subject | Fasting | por |
| dc.subject | FAO | por |
| dc.subject | CREB | por |
| dc.subject | SIRT1 | por |
| dc.subject | Amino-acid deprivation | por |
| dc.title | Fsp27/CIDEC is a CREB target gene induced during fasting and regulated by fatty acid oxidation rate | por |
| dc.type | master thesis | |
| dspace.entity.type | Publication | |
| rcaap.rights | openAccess | por |
| rcaap.type | masterThesis | por |