DLK proteins modulate NOTCHsignaling to influence a brown orwhite 3T3-L1 adipocyte fate

The role of NOTCH signaling in adipogenesis is highly controversial, with data indicating null, positive or negative efects on this diferentiation process. We hypothesize that these contradictory results could be due to the diferent global NOTCH signaling levels obtained in diferent experimental set...

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Autores: Nueda Sanz, María Luisa, González Gómez, María Julia, Rodríguez Cano, María Milagros, Monsalve Argandoña, Eva María, Martínez Díaz-Guerra, María José, Sánchez Solana, Beatriz, Laborda Fernández, Jorge, Baladrón García, Victoriano
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/32192
Acceso en línea:https://hdl.handle.net/10578/32192
Access Level:acceso abierto
Palabra clave:DLK proteins
Adipogenesis
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spelling DLK proteins modulate NOTCHsignaling to influence a brown orwhite 3T3-L1 adipocyte fateNueda Sanz, María LuisaGonzález Gómez, María JuliaRodríguez Cano, María MilagrosMonsalve Argandoña, Eva MaríaMartínez Díaz-Guerra, María JoséSánchez Solana, BeatrizLaborda Fernández, JorgeBaladrón García, VictorianoDLK proteinsAdipogenesisThe role of NOTCH signaling in adipogenesis is highly controversial, with data indicating null, positive or negative efects on this diferentiation process. We hypothesize that these contradictory results could be due to the diferent global NOTCH signaling levels obtained in diferent experimental settings, because of a specifc modulation of NOTCH receptors’ activity by their ligands. We have previously demonstrated that DLK1 and DLK2, two non-canonical NOTCH1 ligands that inhibit NOTCH1 signaling in a dose-dependent manner, modulate the adipogenesis process of 3T3-L1 preadipocytes. In this work, we show that over-expression of any of the four NOTCH receptors enhanced adipogenesis of 3T3-L1 preadipocytes. We also determine that DLK proteins inhibit not only the activity of NOTCH1, but also the activity of NOTCH2, 3 and 4 receptors to diferent degrees. Interestingly, we have observed, by diferent approaches, that NOTCH1 over-expression seems to stimulate the diferentiation of 3T3-L1 cells towards a brown-like adipocyte phenotype, whereas cells over-expressing NOTCH2, 3 or 4 receptors or DLK proteins would rather diferentiate towards a white-like adipocyte phenotype. Finally, our data also demonstrate a complex feed-back mechanism involving Notch and Dlk genes in the regulation of their expression, which suggest that a precise level of global NOTCH expression and NOTCH-dependent transcriptional activity of specifc targets could be necessary to determine the fnal phenotype of 3T3-L1 adipocytes.Springer Nature202320232018info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://hdl.handle.net/10578/32192reponame:RUIdeRA. Repositorio Institucional de la UCLMinstname:Universidad de Castilla-La ManchaInglésBFU2010-16433PII1I09-0164-00PEII11-0062-2456info:eu-repo/semantics/openAccessoai:ruidera.uclm.es:10578/321922026-05-27T07:36:41Z
dc.title.none.fl_str_mv DLK proteins modulate NOTCHsignaling to influence a brown orwhite 3T3-L1 adipocyte fate
title DLK proteins modulate NOTCHsignaling to influence a brown orwhite 3T3-L1 adipocyte fate
spellingShingle DLK proteins modulate NOTCHsignaling to influence a brown orwhite 3T3-L1 adipocyte fate
Nueda Sanz, María Luisa
DLK proteins
Adipogenesis
title_short DLK proteins modulate NOTCHsignaling to influence a brown orwhite 3T3-L1 adipocyte fate
title_full DLK proteins modulate NOTCHsignaling to influence a brown orwhite 3T3-L1 adipocyte fate
title_fullStr DLK proteins modulate NOTCHsignaling to influence a brown orwhite 3T3-L1 adipocyte fate
title_full_unstemmed DLK proteins modulate NOTCHsignaling to influence a brown orwhite 3T3-L1 adipocyte fate
title_sort DLK proteins modulate NOTCHsignaling to influence a brown orwhite 3T3-L1 adipocyte fate
dc.creator.none.fl_str_mv Nueda Sanz, María Luisa
González Gómez, María Julia
Rodríguez Cano, María Milagros
Monsalve Argandoña, Eva María
Martínez Díaz-Guerra, María José
Sánchez Solana, Beatriz
Laborda Fernández, Jorge
Baladrón García, Victoriano
author Nueda Sanz, María Luisa
author_facet Nueda Sanz, María Luisa
González Gómez, María Julia
Rodríguez Cano, María Milagros
Monsalve Argandoña, Eva María
Martínez Díaz-Guerra, María José
Sánchez Solana, Beatriz
Laborda Fernández, Jorge
Baladrón García, Victoriano
author_role author
author2 González Gómez, María Julia
Rodríguez Cano, María Milagros
Monsalve Argandoña, Eva María
Martínez Díaz-Guerra, María José
Sánchez Solana, Beatriz
Laborda Fernández, Jorge
Baladrón García, Victoriano
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DLK proteins
Adipogenesis
topic DLK proteins
Adipogenesis
description The role of NOTCH signaling in adipogenesis is highly controversial, with data indicating null, positive or negative efects on this diferentiation process. We hypothesize that these contradictory results could be due to the diferent global NOTCH signaling levels obtained in diferent experimental settings, because of a specifc modulation of NOTCH receptors’ activity by their ligands. We have previously demonstrated that DLK1 and DLK2, two non-canonical NOTCH1 ligands that inhibit NOTCH1 signaling in a dose-dependent manner, modulate the adipogenesis process of 3T3-L1 preadipocytes. In this work, we show that over-expression of any of the four NOTCH receptors enhanced adipogenesis of 3T3-L1 preadipocytes. We also determine that DLK proteins inhibit not only the activity of NOTCH1, but also the activity of NOTCH2, 3 and 4 receptors to diferent degrees. Interestingly, we have observed, by diferent approaches, that NOTCH1 over-expression seems to stimulate the diferentiation of 3T3-L1 cells towards a brown-like adipocyte phenotype, whereas cells over-expressing NOTCH2, 3 or 4 receptors or DLK proteins would rather diferentiate towards a white-like adipocyte phenotype. Finally, our data also demonstrate a complex feed-back mechanism involving Notch and Dlk genes in the regulation of their expression, which suggest that a precise level of global NOTCH expression and NOTCH-dependent transcriptional activity of specifc targets could be necessary to determine the fnal phenotype of 3T3-L1 adipocytes.
publishDate 2018
dc.date.none.fl_str_mv 2018
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10578/32192
url https://hdl.handle.net/10578/32192
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv BFU2010-16433
PII1I09-0164-00
PEII11-0062-2456
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:RUIdeRA. Repositorio Institucional de la UCLM
instname:Universidad de Castilla-La Mancha
instname_str Universidad de Castilla-La Mancha
reponame_str RUIdeRA. Repositorio Institucional de la UCLM
collection RUIdeRA. Repositorio Institucional de la UCLM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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