Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness

Recently thioredoxin reductase 1 (TrxR1), encoded by Txnrd1, was suggested to modulate glucose and lipid metabolism in mice. Here we discovered that TrxR1 suppresses insulin responsiveness, anabolic metabolism and adipocyte differentiation. Immortalized mouse embryonic fibroblasts (MEFs) lacking Txn...

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Detalles Bibliográficos
Autores: Peng, Xiaoxiao, Giménez-Cassina, Alfredo, Petrus, Paul, Conrad, Marcus, Rydén, Mikael, Arnér, Elias S. J.
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/679319
Acceso en línea:http://hdl.handle.net/10486/679319
https://dx.doi.org/10.1038/srep28080
Access Level:acceso abierto
Palabra clave:Biochemistry
Cell biology
Insulin signalling
Biología y Biomedicina / Biología
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spelling Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsivenessPeng, XiaoxiaoGiménez-Cassina, AlfredoPetrus, PaulConrad, MarcusRydén, MikaelArnér, Elias S. J.BiochemistryCell biologyInsulin signallingBiología y Biomedicina / BiologíaRecently thioredoxin reductase 1 (TrxR1), encoded by Txnrd1, was suggested to modulate glucose and lipid metabolism in mice. Here we discovered that TrxR1 suppresses insulin responsiveness, anabolic metabolism and adipocyte differentiation. Immortalized mouse embryonic fibroblasts (MEFs) lacking Txnrd1 (Txnrd1−/−) displayed increased metabolic flux, glycogen storage, lipogenesis and adipogenesis. This phenotype coincided with upregulated PPARγ expression, promotion of mitotic clonal expansion and downregulation of p27 and p53. Enhanced Akt activation also contributed to augmented adipogenesis and insulin sensitivity. Knockdown of TXNRD1 transcripts accelerated adipocyte differentiation also in human primary preadipocytes. Furthermore, TXNRD1 transcript levels in subcutaneous adipose tissue from 56 women were inversely associated with insulin sensitivity in vivo and lipogenesis in their isolated adipocytes. These results suggest that TrxR1 suppresses anabolic metabolism and adipogenesis by inhibition of intracellular signaling pathways downstream of insulin stimulationThis study was supported by funding to ESJA from Karolinska Institutet, The Swedish Research Council, The Swedish Cancer Society, to MR from the Strategic Research Program in Diabetes and to ACG from Diabetesfonden and a “Ramón y Cajal” fellowship (RYC-2014-15792) from Spanish Ministerio de Economía y CompetitividadNature Publishing GroupDepartamento de Biología MolecularFacultad de Ciencias20162016-06-27research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/679319https://dx.doi.org/10.1038/srep28080reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6793192026-06-23T12:46:27Z
dc.title.none.fl_str_mv Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness
title Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness
spellingShingle Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness
Peng, Xiaoxiao
Biochemistry
Cell biology
Insulin signalling
Biología y Biomedicina / Biología
title_short Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness
title_full Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness
title_fullStr Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness
title_full_unstemmed Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness
title_sort Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness
dc.creator.none.fl_str_mv Peng, Xiaoxiao
Giménez-Cassina, Alfredo
Petrus, Paul
Conrad, Marcus
Rydén, Mikael
Arnér, Elias S. J.
author Peng, Xiaoxiao
author_facet Peng, Xiaoxiao
Giménez-Cassina, Alfredo
Petrus, Paul
Conrad, Marcus
Rydén, Mikael
Arnér, Elias S. J.
author_role author
author2 Giménez-Cassina, Alfredo
Petrus, Paul
Conrad, Marcus
Rydén, Mikael
Arnér, Elias S. J.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv Biochemistry
Cell biology
Insulin signalling
Biología y Biomedicina / Biología
topic Biochemistry
Cell biology
Insulin signalling
Biología y Biomedicina / Biología
description Recently thioredoxin reductase 1 (TrxR1), encoded by Txnrd1, was suggested to modulate glucose and lipid metabolism in mice. Here we discovered that TrxR1 suppresses insulin responsiveness, anabolic metabolism and adipocyte differentiation. Immortalized mouse embryonic fibroblasts (MEFs) lacking Txnrd1 (Txnrd1−/−) displayed increased metabolic flux, glycogen storage, lipogenesis and adipogenesis. This phenotype coincided with upregulated PPARγ expression, promotion of mitotic clonal expansion and downregulation of p27 and p53. Enhanced Akt activation also contributed to augmented adipogenesis and insulin sensitivity. Knockdown of TXNRD1 transcripts accelerated adipocyte differentiation also in human primary preadipocytes. Furthermore, TXNRD1 transcript levels in subcutaneous adipose tissue from 56 women were inversely associated with insulin sensitivity in vivo and lipogenesis in their isolated adipocytes. These results suggest that TrxR1 suppresses anabolic metabolism and adipogenesis by inhibition of intracellular signaling pathways downstream of insulin stimulation
publishDate 2016
dc.date.none.fl_str_mv 2016
2016-06-27
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/679319
https://dx.doi.org/10.1038/srep28080
url http://hdl.handle.net/10486/679319
https://dx.doi.org/10.1038/srep28080
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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