NT3/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent Adipose Tissue.

Neurotrophin-3 (NT3), through activation of its tropomyosin-related kinase receptor C (TrkC), modulates neuronal survival and neural stem cell differentiation. It is widely distributed in peripheral tissues (especially vessels and pancreas) and this ubiquitous pattern suggests a role for NT3, outsid...

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Autores: Bove, M, Monto, F, Guillem-Llobat, P, Ivorra, MD, Noguera, MA, Zambrano, A, Sirerol-Piquer, MS, Requena, AC, Garcia-Alonso, M, Tejerina, T, Real, JT, Farinas, I, D'Ocon, P
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p16176
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/16176
Access Level:acceso abierto
Palabra clave:UCP-1
adipocytes
beta-adrenoceptors
brown adipose tissue
neurotrophin-3
tropomyosin-related kinase receptor C
white adipose tissue
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spelling NT3/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent Adipose Tissue.Bove, MMonto, FGuillem-Llobat, PIvorra, MDNoguera, MAZambrano, ASirerol-Piquer, MSRequena, ACGarcia-Alonso, MTejerina, TReal, JTFarinas, ID'Ocon, PUCP-1adipocytesbeta-adrenoceptorsbrown adipose tissueneurotrophin-3tropomyosin-related kinase receptor Cwhite adipose tissueNeurotrophin-3 (NT3), through activation of its tropomyosin-related kinase receptor C (TrkC), modulates neuronal survival and neural stem cell differentiation. It is widely distributed in peripheral tissues (especially vessels and pancreas) and this ubiquitous pattern suggests a role for NT3, outside the nervous system and related to metabolic functions. The presence of the NT3/TrkC pathway in the adipose tissue (AT) has never been investigated. Present work studies in human and murine adipose tissue (AT) the presence of elements of the NT3/TrkC pathway and its role on lipolysis and adipocyte differentiation. qRT-PCR and immunoblot indicate that NT3 (encoded by NTF3) was present in human retroperitoneal AT and decreases with age. NT3 was also present in rat isolated adipocytes and retroperitoneal, interscapular, perivascular, and perirenal AT. Histological analysis evidences that NT3 was mainly present in vessels irrigating AT close associated to sympathetic fibers. Similar mRNA levels of TrkC (encoded by NTRK3) and ß-adrenoceptors were found in all ATs assayed and in isolated adipocytes. NT3, through TrkC activation, exert a mild effect in lipolysis. Addition of NT3 during the differentiation process of human pre-adipocytes resulted in smaller adipocytes and increased uncoupling protein-1 (UCP-1) without changes in ß-adrenoceptors. Similarly, transgenic mice with reduced expression of NT3 (Ntf3 knock-in lacZ reporter mice) or lacking endothelial NT3 expression (Ntf3flox1/flox2;Tie2-Cre+/0) displayed enlarged white and brown adipocytes and lower UCP-1 expression. CONCLUSIONS: NT3, mainly released by blood vessels, activates TrkC and regulates adipocyte differentiation and browning. Disruption of NT3/TrkC signaling conducts to hypertrophied white and brown adipocytes with reduced expression of the thermogenesis marker UCP-1.FRONTIERS MEDIA SA2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/16176Frontiers in EndocrinologyISSN: 16642392reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p161762026-06-07T16:35:31Z
dc.title.none.fl_str_mv NT3/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent Adipose Tissue.
title NT3/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent Adipose Tissue.
spellingShingle NT3/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent Adipose Tissue.
Bove, M
UCP-1
adipocytes
beta-adrenoceptors
brown adipose tissue
neurotrophin-3
tropomyosin-related kinase receptor C
white adipose tissue
title_short NT3/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent Adipose Tissue.
title_full NT3/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent Adipose Tissue.
title_fullStr NT3/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent Adipose Tissue.
title_full_unstemmed NT3/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent Adipose Tissue.
title_sort NT3/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent Adipose Tissue.
dc.creator.none.fl_str_mv Bove, M
Monto, F
Guillem-Llobat, P
Ivorra, MD
Noguera, MA
Zambrano, A
Sirerol-Piquer, MS
Requena, AC
Garcia-Alonso, M
Tejerina, T
Real, JT
Farinas, I
D'Ocon, P
author Bove, M
author_facet Bove, M
Monto, F
Guillem-Llobat, P
Ivorra, MD
Noguera, MA
Zambrano, A
Sirerol-Piquer, MS
Requena, AC
Garcia-Alonso, M
Tejerina, T
Real, JT
Farinas, I
D'Ocon, P
author_role author
author2 Monto, F
Guillem-Llobat, P
Ivorra, MD
Noguera, MA
Zambrano, A
Sirerol-Piquer, MS
Requena, AC
Garcia-Alonso, M
Tejerina, T
Real, JT
Farinas, I
D'Ocon, P
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv UCP-1
adipocytes
beta-adrenoceptors
brown adipose tissue
neurotrophin-3
tropomyosin-related kinase receptor C
white adipose tissue
topic UCP-1
adipocytes
beta-adrenoceptors
brown adipose tissue
neurotrophin-3
tropomyosin-related kinase receptor C
white adipose tissue
description Neurotrophin-3 (NT3), through activation of its tropomyosin-related kinase receptor C (TrkC), modulates neuronal survival and neural stem cell differentiation. It is widely distributed in peripheral tissues (especially vessels and pancreas) and this ubiquitous pattern suggests a role for NT3, outside the nervous system and related to metabolic functions. The presence of the NT3/TrkC pathway in the adipose tissue (AT) has never been investigated. Present work studies in human and murine adipose tissue (AT) the presence of elements of the NT3/TrkC pathway and its role on lipolysis and adipocyte differentiation. qRT-PCR and immunoblot indicate that NT3 (encoded by NTF3) was present in human retroperitoneal AT and decreases with age. NT3 was also present in rat isolated adipocytes and retroperitoneal, interscapular, perivascular, and perirenal AT. Histological analysis evidences that NT3 was mainly present in vessels irrigating AT close associated to sympathetic fibers. Similar mRNA levels of TrkC (encoded by NTRK3) and ß-adrenoceptors were found in all ATs assayed and in isolated adipocytes. NT3, through TrkC activation, exert a mild effect in lipolysis. Addition of NT3 during the differentiation process of human pre-adipocytes resulted in smaller adipocytes and increased uncoupling protein-1 (UCP-1) without changes in ß-adrenoceptors. Similarly, transgenic mice with reduced expression of NT3 (Ntf3 knock-in lacZ reporter mice) or lacking endothelial NT3 expression (Ntf3flox1/flox2;Tie2-Cre+/0) displayed enlarged white and brown adipocytes and lower UCP-1 expression. CONCLUSIONS: NT3, mainly released by blood vessels, activates TrkC and regulates adipocyte differentiation and browning. Disruption of NT3/TrkC signaling conducts to hypertrophied white and brown adipocytes with reduced expression of the thermogenesis marker UCP-1.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://incliva.portalinvestigacion.com/publicaciones/16176
url https://incliva.portalinvestigacion.com/publicaciones/16176
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv FRONTIERS MEDIA SA
publisher.none.fl_str_mv FRONTIERS MEDIA SA
dc.source.none.fl_str_mv Frontiers in Endocrinology
ISSN: 16642392
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
repository.name.fl_str_mv
repository.mail.fl_str_mv
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