The E2F2 Transcription Factor Sustains Hepatic Glycerophospholipid Homeostasis in Mice

Autores
Maldonado, Eduardo N.; Delgado, Igotz; Furland, Natalia Edith; Buqué, Xabier; Iglesias, Ainhoa; Aveldaño, Marta Isabel; Zubiaga, Ana; Fresnedo, Olatz; Ocho, Begoña
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Increasing evidence links metabolic signals to cell proliferation, but the molecular wiring that connects the two core machineries remains largely unknown. E2Fs are master regulators of cellular proliferation. We have recently shown that E2F2 activity facilitates the completion of liver regeneration after partial hepatectomy (PH) by regulating the expression of genes required for S-phase entry. Our study also revealed that E2F2 determines the duration of hepatectomy-induced hepatic steatosis. A transcriptomic analysis of normal adult liver identified "lipid metabolism regulation" as a major E2F2 functional target, suggesting that E2F2 has a role in lipid homeostasis. Here we use wild-type (E2F2+/+) and E2F2 deficient (E2F2-/-) mice to investigate the in vivo role of E2F2 in the composition of liver lipids and fatty acids in two metabolically different contexts: quiescence and 48-h post-PH, when cellular proliferation and anabolic demands are maximal. We show that liver regeneration is accompanied by large triglyceride and protein increases without changes in total phospholipids both in E2F2+/+ and E2F2-/- mice. Remarkably, we found that the phenotype of quiescent liver tissue from E2F2-/- mice resembles the phenotype of proliferating E2F2+/+ liver tissue, characterized by a decreased phosphatidylcholine to phosphatidylethanolamine ratio and a reprogramming of genes involved in generation of choline and ethanolamine derivatives. The diversity of fatty acids in total lipid, triglycerides and phospholipids was essentially preserved on E2F2 loss both in proliferating and non-proliferating liver tissue, although notable exceptions in inflammation-related fatty acids of defined phospholipid classes were detected. Overall, our results indicate that E2F2 activity sustains the hepatic homeostasis of major membrane glycerolipid components while it is dispensable for storage glycerolipid balance.
Fil: Maldonado, Eduardo N.. Universidad del Pais Vasco; España
Fil: Delgado, Igotz. University Of The Basque Country (upv/ehu). Department Of Chemical And Environmental Engineering, Polytechnic School; España
Fil: Furland, Natalia Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Buqué, Xabier. Universidad del Pais Vasco; España
Fil: Iglesias, Ainhoa. Universidad del Pais Vasco; España
Fil: Aveldaño, Marta Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Zubiaga, Ana. Universidad del Pais Vasco; España
Fil: Fresnedo, Olatz. Universidad del Pais Vasco; España
Fil: Ocho, Begoña. Universidad del Pais Vasco; España
Materia
CELLS MEMBRANES
FATTY ACIDS
FATTY LIVER
GENE EXPRESSION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/4506
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/4506
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The E2F2 Transcription Factor Sustains Hepatic Glycerophospholipid Homeostasis in MiceMaldonado, Eduardo N.Delgado, IgotzFurland, Natalia EdithBuqué, XabierIglesias, AinhoaAveldaño, Marta IsabelZubiaga, AnaFresnedo, OlatzOcho, BegoñaCELLS MEMBRANESFATTY ACIDSFATTY LIVERGENE EXPRESSIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Increasing evidence links metabolic signals to cell proliferation, but the molecular wiring that connects the two core machineries remains largely unknown. E2Fs are master regulators of cellular proliferation. We have recently shown that E2F2 activity facilitates the completion of liver regeneration after partial hepatectomy (PH) by regulating the expression of genes required for S-phase entry. Our study also revealed that E2F2 determines the duration of hepatectomy-induced hepatic steatosis. A transcriptomic analysis of normal adult liver identified "lipid metabolism regulation" as a major E2F2 functional target, suggesting that E2F2 has a role in lipid homeostasis. Here we use wild-type (E2F2+/+) and E2F2 deficient (E2F2-/-) mice to investigate the in vivo role of E2F2 in the composition of liver lipids and fatty acids in two metabolically different contexts: quiescence and 48-h post-PH, when cellular proliferation and anabolic demands are maximal. We show that liver regeneration is accompanied by large triglyceride and protein increases without changes in total phospholipids both in E2F2+/+ and E2F2-/- mice. Remarkably, we found that the phenotype of quiescent liver tissue from E2F2-/- mice resembles the phenotype of proliferating E2F2+/+ liver tissue, characterized by a decreased phosphatidylcholine to phosphatidylethanolamine ratio and a reprogramming of genes involved in generation of choline and ethanolamine derivatives. The diversity of fatty acids in total lipid, triglycerides and phospholipids was essentially preserved on E2F2 loss both in proliferating and non-proliferating liver tissue, although notable exceptions in inflammation-related fatty acids of defined phospholipid classes were detected. Overall, our results indicate that E2F2 activity sustains the hepatic homeostasis of major membrane glycerolipid components while it is dispensable for storage glycerolipid balance.Fil: Maldonado, Eduardo N.. Universidad del Pais Vasco; EspañaFil: Delgado, Igotz. University Of The Basque Country (upv/ehu). Department Of Chemical And Environmental Engineering, Polytechnic School; EspañaFil: Furland, Natalia Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); ArgentinaFil: Buqué, Xabier. Universidad del Pais Vasco; EspañaFil: Iglesias, Ainhoa. Universidad del Pais Vasco; EspañaFil: Aveldaño, Marta Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); ArgentinaFil: Zubiaga, Ana. Universidad del Pais Vasco; EspañaFil: Fresnedo, Olatz. Universidad del Pais Vasco; EspañaFil: Ocho, Begoña. Universidad del Pais Vasco; EspañaPublic Library Of Science2014-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/4506Maldonado, Eduardo N.; Delgado, Igotz; Furland, Natalia Edith; Buqué, Xabier; Iglesias, Ainhoa; et al.; The E2F2 Transcription Factor Sustains Hepatic Glycerophospholipid Homeostasis in Mice; Public Library Of Science; Plos One; 9; 11; 11-2014; e1126201932-6203enginfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0112620info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:00:20Zoai:ri.conicet.gov.ar:11336/4506instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:00:20.369CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The E2F2 Transcription Factor Sustains Hepatic Glycerophospholipid Homeostasis in Mice
title The E2F2 Transcription Factor Sustains Hepatic Glycerophospholipid Homeostasis in Mice
spellingShingle The E2F2 Transcription Factor Sustains Hepatic Glycerophospholipid Homeostasis in Mice
Maldonado, Eduardo N.
CELLS MEMBRANES
FATTY ACIDS
FATTY LIVER
GENE EXPRESSION
title_short The E2F2 Transcription Factor Sustains Hepatic Glycerophospholipid Homeostasis in Mice
title_full The E2F2 Transcription Factor Sustains Hepatic Glycerophospholipid Homeostasis in Mice
title_fullStr The E2F2 Transcription Factor Sustains Hepatic Glycerophospholipid Homeostasis in Mice
title_full_unstemmed The E2F2 Transcription Factor Sustains Hepatic Glycerophospholipid Homeostasis in Mice
title_sort The E2F2 Transcription Factor Sustains Hepatic Glycerophospholipid Homeostasis in Mice
dc.creator.none.fl_str_mv Maldonado, Eduardo N.
Delgado, Igotz
Furland, Natalia Edith
Buqué, Xabier
Iglesias, Ainhoa
Aveldaño, Marta Isabel
Zubiaga, Ana
Fresnedo, Olatz
Ocho, Begoña
author Maldonado, Eduardo N.
author_facet Maldonado, Eduardo N.
Delgado, Igotz
Furland, Natalia Edith
Buqué, Xabier
Iglesias, Ainhoa
Aveldaño, Marta Isabel
Zubiaga, Ana
Fresnedo, Olatz
Ocho, Begoña
author_role author
author2 Delgado, Igotz
Furland, Natalia Edith
Buqué, Xabier
Iglesias, Ainhoa
Aveldaño, Marta Isabel
Zubiaga, Ana
Fresnedo, Olatz
Ocho, Begoña
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CELLS MEMBRANES
FATTY ACIDS
FATTY LIVER
GENE EXPRESSION
topic CELLS MEMBRANES
FATTY ACIDS
FATTY LIVER
GENE EXPRESSION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Increasing evidence links metabolic signals to cell proliferation, but the molecular wiring that connects the two core machineries remains largely unknown. E2Fs are master regulators of cellular proliferation. We have recently shown that E2F2 activity facilitates the completion of liver regeneration after partial hepatectomy (PH) by regulating the expression of genes required for S-phase entry. Our study also revealed that E2F2 determines the duration of hepatectomy-induced hepatic steatosis. A transcriptomic analysis of normal adult liver identified "lipid metabolism regulation" as a major E2F2 functional target, suggesting that E2F2 has a role in lipid homeostasis. Here we use wild-type (E2F2+/+) and E2F2 deficient (E2F2-/-) mice to investigate the in vivo role of E2F2 in the composition of liver lipids and fatty acids in two metabolically different contexts: quiescence and 48-h post-PH, when cellular proliferation and anabolic demands are maximal. We show that liver regeneration is accompanied by large triglyceride and protein increases without changes in total phospholipids both in E2F2+/+ and E2F2-/- mice. Remarkably, we found that the phenotype of quiescent liver tissue from E2F2-/- mice resembles the phenotype of proliferating E2F2+/+ liver tissue, characterized by a decreased phosphatidylcholine to phosphatidylethanolamine ratio and a reprogramming of genes involved in generation of choline and ethanolamine derivatives. The diversity of fatty acids in total lipid, triglycerides and phospholipids was essentially preserved on E2F2 loss both in proliferating and non-proliferating liver tissue, although notable exceptions in inflammation-related fatty acids of defined phospholipid classes were detected. Overall, our results indicate that E2F2 activity sustains the hepatic homeostasis of major membrane glycerolipid components while it is dispensable for storage glycerolipid balance.
Fil: Maldonado, Eduardo N.. Universidad del Pais Vasco; España
Fil: Delgado, Igotz. University Of The Basque Country (upv/ehu). Department Of Chemical And Environmental Engineering, Polytechnic School; España
Fil: Furland, Natalia Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Buqué, Xabier. Universidad del Pais Vasco; España
Fil: Iglesias, Ainhoa. Universidad del Pais Vasco; España
Fil: Aveldaño, Marta Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Zubiaga, Ana. Universidad del Pais Vasco; España
Fil: Fresnedo, Olatz. Universidad del Pais Vasco; España
Fil: Ocho, Begoña. Universidad del Pais Vasco; España
description Increasing evidence links metabolic signals to cell proliferation, but the molecular wiring that connects the two core machineries remains largely unknown. E2Fs are master regulators of cellular proliferation. We have recently shown that E2F2 activity facilitates the completion of liver regeneration after partial hepatectomy (PH) by regulating the expression of genes required for S-phase entry. Our study also revealed that E2F2 determines the duration of hepatectomy-induced hepatic steatosis. A transcriptomic analysis of normal adult liver identified "lipid metabolism regulation" as a major E2F2 functional target, suggesting that E2F2 has a role in lipid homeostasis. Here we use wild-type (E2F2+/+) and E2F2 deficient (E2F2-/-) mice to investigate the in vivo role of E2F2 in the composition of liver lipids and fatty acids in two metabolically different contexts: quiescence and 48-h post-PH, when cellular proliferation and anabolic demands are maximal. We show that liver regeneration is accompanied by large triglyceride and protein increases without changes in total phospholipids both in E2F2+/+ and E2F2-/- mice. Remarkably, we found that the phenotype of quiescent liver tissue from E2F2-/- mice resembles the phenotype of proliferating E2F2+/+ liver tissue, characterized by a decreased phosphatidylcholine to phosphatidylethanolamine ratio and a reprogramming of genes involved in generation of choline and ethanolamine derivatives. The diversity of fatty acids in total lipid, triglycerides and phospholipids was essentially preserved on E2F2 loss both in proliferating and non-proliferating liver tissue, although notable exceptions in inflammation-related fatty acids of defined phospholipid classes were detected. Overall, our results indicate that E2F2 activity sustains the hepatic homeostasis of major membrane glycerolipid components while it is dispensable for storage glycerolipid balance.
publishDate 2014
dc.date.none.fl_str_mv 2014-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/4506
Maldonado, Eduardo N.; Delgado, Igotz; Furland, Natalia Edith; Buqué, Xabier; Iglesias, Ainhoa; et al.; The E2F2 Transcription Factor Sustains Hepatic Glycerophospholipid Homeostasis in Mice; Public Library Of Science; Plos One; 9; 11; 11-2014; e112620
1932-6203
url http://hdl.handle.net/11336/4506
identifier_str_mv Maldonado, Eduardo N.; Delgado, Igotz; Furland, Natalia Edith; Buqué, Xabier; Iglesias, Ainhoa; et al.; The E2F2 Transcription Factor Sustains Hepatic Glycerophospholipid Homeostasis in Mice; Public Library Of Science; Plos One; 9; 11; 11-2014; e112620
1932-6203
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0112620
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library Of Science
publisher.none.fl_str_mv Public Library Of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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