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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Frontiers Media S.A.
2021-03-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2021.630097/full |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
María Bové María Bové Fermi Monto Fermi Monto Paloma Guillem-Llobat Paloma Guillem-Llobat M Dolores Ivorra M Dolores Ivorra M Antonia Noguera M Antonia Noguera Andrea Zambrano Andrea Zambrano M Salome Sirerol-Piquer M Salome Sirerol-Piquer M Salome Sirerol-Piquer Ana Cristina Requena Mauricio García-Alonso Teresa Tejerina Teresa Tejerina José T. Real José T. Real José T. Real Isabel Fariñas Isabel Fariñas Isabel Fariñas Pilar D’Ocon Pilar D’Ocon |
spellingShingle |
María Bové María Bové Fermi Monto Fermi Monto Paloma Guillem-Llobat Paloma Guillem-Llobat M Dolores Ivorra M Dolores Ivorra M Antonia Noguera M Antonia Noguera Andrea Zambrano Andrea Zambrano M Salome Sirerol-Piquer M Salome Sirerol-Piquer M Salome Sirerol-Piquer Ana Cristina Requena Mauricio García-Alonso Teresa Tejerina Teresa Tejerina José T. Real José T. Real José T. Real Isabel Fariñas Isabel Fariñas Isabel Fariñas Pilar D’Ocon Pilar D’Ocon NT3/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent Adipose Tissue Frontiers in Endocrinology neurotrophin-3 tropomyosin-related kinase receptor C beta-adrenoceptors white adipose tissue brown adipose tissue adipocytes |
author_facet |
María Bové María Bové Fermi Monto Fermi Monto Paloma Guillem-Llobat Paloma Guillem-Llobat M Dolores Ivorra M Dolores Ivorra M Antonia Noguera M Antonia Noguera Andrea Zambrano Andrea Zambrano M Salome Sirerol-Piquer M Salome Sirerol-Piquer M Salome Sirerol-Piquer Ana Cristina Requena Mauricio García-Alonso Teresa Tejerina Teresa Tejerina José T. Real José T. Real José T. Real Isabel Fariñas Isabel Fariñas Isabel Fariñas Pilar D’Ocon Pilar D’Ocon |
author_sort |
María Bové |
title |
NT3/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent 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 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Endocrinology |
issn |
1664-2392 |
publishDate |
2021-03-01 |
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 β-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 β-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.ConclusionsNT3, 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. |
topic |
neurotrophin-3 tropomyosin-related kinase receptor C beta-adrenoceptors white adipose tissue brown adipose tissue adipocytes |
url |
https://www.frontiersin.org/articles/10.3389/fendo.2021.630097/full |
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doaj-a48f19f2d4c1487abe3bf6fef9510af92021-03-18T16:38:46ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-03-011210.3389/fendo.2021.630097630097NT3/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent Adipose TissueMaría Bové0María Bové1Fermi Monto2Fermi Monto3Paloma Guillem-Llobat4Paloma Guillem-Llobat5M Dolores Ivorra6M Dolores Ivorra7M Antonia Noguera8M Antonia Noguera9Andrea Zambrano10Andrea Zambrano11M Salome Sirerol-Piquer12M Salome Sirerol-Piquer13M Salome Sirerol-Piquer14Ana Cristina Requena15Mauricio García-Alonso16Teresa Tejerina17Teresa Tejerina18José T. Real19José T. Real20José T. Real21Isabel Fariñas22Isabel Fariñas23Isabel Fariñas24Pilar D’Ocon25Pilar D’Ocon26Departamento de Farmacología, Facultad de Farmacia, Universidad de Valencia, Valencia, SpainEstructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (ERI BIOTECMED), Universidad de Valencia, Valencia, SpainDepartamento de Farmacología, Facultad de Farmacia, Universidad de Valencia, Valencia, SpainEstructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (ERI BIOTECMED), Universidad de Valencia, Valencia, SpainDepartamento de Farmacología, Facultad de Farmacia, Universidad de Valencia, Valencia, SpainEstructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (ERI BIOTECMED), Universidad de Valencia, Valencia, SpainDepartamento de Farmacología, Facultad de Farmacia, Universidad de Valencia, Valencia, SpainEstructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (ERI BIOTECMED), Universidad de Valencia, Valencia, SpainDepartamento de Farmacología, Facultad de Farmacia, Universidad de Valencia, Valencia, SpainEstructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (ERI BIOTECMED), Universidad de Valencia, Valencia, SpainDepartamento de Farmacología, Facultad de Farmacia, Universidad de Valencia, Valencia, SpainEstructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (ERI BIOTECMED), Universidad de Valencia, Valencia, SpainEstructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (ERI BIOTECMED), Universidad de Valencia, Valencia, SpainDepartamento de Biología Celular, Biología Funcional y Antropología Física, Universidad de Valencia, Valencia, SpainCIBER en Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainDepartamento de Biología Celular, Biología Funcional y Antropología Física, Universidad de Valencia, Valencia, SpainServicio de Cirugía General y Aparato Digestivo, Hospital Clínico San Carlos, Madrid, SpainServicio de Cirugía General y Aparato Digestivo, Hospital Clínico San Carlos, Madrid, SpainDepartamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, SpainCIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, SpainServicio de Endocrinología y Nutrición, Hospital Clínico Universitario e INCLIVA, Valencia, SpainDepartamento de Medicina, Facultad de Medicina, Universidad de Valencia, Valencia, SpainEstructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (ERI BIOTECMED), Universidad de Valencia, Valencia, SpainDepartamento de Biología Celular, Biología Funcional y Antropología Física, Universidad de Valencia, Valencia, SpainCIBER en Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainDepartamento de Farmacología, Facultad de Farmacia, Universidad de Valencia, Valencia, SpainEstructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (ERI BIOTECMED), Universidad de Valencia, Valencia, SpainNeurotrophin-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 β-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 β-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.ConclusionsNT3, 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.https://www.frontiersin.org/articles/10.3389/fendo.2021.630097/fullneurotrophin-3tropomyosin-related kinase receptor Cbeta-adrenoceptorswhite adipose tissuebrown adipose tissueadipocytes |