Cargando…

Identification of Creb3l4 as an essential negative regulator of adipogenesis

Understanding the molecular networks that regulate adipogenesis is crucial for combating obesity. However, the identity and molecular actions of negative regulators that regulate the early development of adipocytes remain poorly understood. In this study, we investigated the role of CREB3L4, a membe...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, T-H, Jo, S-H, Choi, H, Park, J-M, Kim, M-Y, Nojima, H, Kim, J-W, Ahn, Y-H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260748/
https://www.ncbi.nlm.nih.gov/pubmed/25412305
http://dx.doi.org/10.1038/cddis.2014.490
_version_ 1782348216675598336
author Kim, T-H
Jo, S-H
Choi, H
Park, J-M
Kim, M-Y
Nojima, H
Kim, J-W
Ahn, Y-H
author_facet Kim, T-H
Jo, S-H
Choi, H
Park, J-M
Kim, M-Y
Nojima, H
Kim, J-W
Ahn, Y-H
author_sort Kim, T-H
collection PubMed
description Understanding the molecular networks that regulate adipogenesis is crucial for combating obesity. However, the identity and molecular actions of negative regulators that regulate the early development of adipocytes remain poorly understood. In this study, we investigated the role of CREB3L4, a member of the CREB3-like family, in the regulation of adiposity. Constitutive overexpression of CREB3L4 resulted in the inhibition of adipocyte differentiation, whereas knockdown of Creb3l4 expression caused differentiation of preadipocytes into mature adipocytes, bypassing the mitotic clonal expansion step. In 3T3-L1 preadipocytes, Creb3l4 knockdown resulted in increased expression of peroxisome proliferator-activated receptor γ (PPARγ2) and CCAAT/enhancer binding protein (C/EBPα), either by increasing the protein stability of C/EBPβ or by decreasing the expression of GATA3, a negative regulator of PPARγ2 expression. Consequently, increased PPARγ2 and C/EBPα levels induced adipocyte differentiation, even in the presence of minimal hormonal inducer. Thus, it can be speculated that CREB3L4 has a role as gatekeeper, inhibiting adipogenesis in 3T3-L1 preadipocytes. Moreover, adipocytes of Creb3l4-knockout mice showed hyperplasia caused by increased adipogenesis, and exhibited improved glucose tolerance and insulin sensitivity, as compared with littermate wild-type mice. These results raise the possibility that Creb3l4 could be a useful therapeutic target in the fight against obesity and metabolic syndrome.
format Online
Article
Text
id pubmed-4260748
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-42607482014-12-15 Identification of Creb3l4 as an essential negative regulator of adipogenesis Kim, T-H Jo, S-H Choi, H Park, J-M Kim, M-Y Nojima, H Kim, J-W Ahn, Y-H Cell Death Dis Original Article Understanding the molecular networks that regulate adipogenesis is crucial for combating obesity. However, the identity and molecular actions of negative regulators that regulate the early development of adipocytes remain poorly understood. In this study, we investigated the role of CREB3L4, a member of the CREB3-like family, in the regulation of adiposity. Constitutive overexpression of CREB3L4 resulted in the inhibition of adipocyte differentiation, whereas knockdown of Creb3l4 expression caused differentiation of preadipocytes into mature adipocytes, bypassing the mitotic clonal expansion step. In 3T3-L1 preadipocytes, Creb3l4 knockdown resulted in increased expression of peroxisome proliferator-activated receptor γ (PPARγ2) and CCAAT/enhancer binding protein (C/EBPα), either by increasing the protein stability of C/EBPβ or by decreasing the expression of GATA3, a negative regulator of PPARγ2 expression. Consequently, increased PPARγ2 and C/EBPα levels induced adipocyte differentiation, even in the presence of minimal hormonal inducer. Thus, it can be speculated that CREB3L4 has a role as gatekeeper, inhibiting adipogenesis in 3T3-L1 preadipocytes. Moreover, adipocytes of Creb3l4-knockout mice showed hyperplasia caused by increased adipogenesis, and exhibited improved glucose tolerance and insulin sensitivity, as compared with littermate wild-type mice. These results raise the possibility that Creb3l4 could be a useful therapeutic target in the fight against obesity and metabolic syndrome. Nature Publishing Group 2014-11 2014-11-20 /pmc/articles/PMC4260748/ /pubmed/25412305 http://dx.doi.org/10.1038/cddis.2014.490 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International Licence. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Kim, T-H
Jo, S-H
Choi, H
Park, J-M
Kim, M-Y
Nojima, H
Kim, J-W
Ahn, Y-H
Identification of Creb3l4 as an essential negative regulator of adipogenesis
title Identification of Creb3l4 as an essential negative regulator of adipogenesis
title_full Identification of Creb3l4 as an essential negative regulator of adipogenesis
title_fullStr Identification of Creb3l4 as an essential negative regulator of adipogenesis
title_full_unstemmed Identification of Creb3l4 as an essential negative regulator of adipogenesis
title_short Identification of Creb3l4 as an essential negative regulator of adipogenesis
title_sort identification of creb3l4 as an essential negative regulator of adipogenesis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260748/
https://www.ncbi.nlm.nih.gov/pubmed/25412305
http://dx.doi.org/10.1038/cddis.2014.490
work_keys_str_mv AT kimth identificationofcreb3l4asanessentialnegativeregulatorofadipogenesis
AT josh identificationofcreb3l4asanessentialnegativeregulatorofadipogenesis
AT choih identificationofcreb3l4asanessentialnegativeregulatorofadipogenesis
AT parkjm identificationofcreb3l4asanessentialnegativeregulatorofadipogenesis
AT kimmy identificationofcreb3l4asanessentialnegativeregulatorofadipogenesis
AT nojimah identificationofcreb3l4asanessentialnegativeregulatorofadipogenesis
AT kimjw identificationofcreb3l4asanessentialnegativeregulatorofadipogenesis
AT ahnyh identificationofcreb3l4asanessentialnegativeregulatorofadipogenesis