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...
| Autores: | , , , , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2018 |
| País: | España |
| Recursos: | Universidad de Castilla-La Mancha |
| Repositorio: | RUIdeRA. Repositorio Institucional de la UCLM |
| OAI Identifier: | oai:ruidera.uclm.es:10578/32192 |
| Acesso em linha: | https://hdl.handle.net/10578/32192 |
| Access Level: | acceso abierto |
| Palavra-chave: | DLK proteins Adipogenesis |
| Resumo: | 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. |
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