PKN1 Kinase: A Key Player in Adipocyte Differentiation and Glucose Metabolism

Adipocyte dysfunction is the driver of obesity and correlates with insulin resistance and the onset of type 2 diabetes. Protein kinase N1 (PKN1) is a serine/threonine kinase that has been shown to contribute to Glut4 translocation to the membrane and glucose transport. Here, we evaluated the role of...

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Autores: Herrerías González, Fernando, Yeramian Hakim, Andree, Baena-Fustegueras, Juan A, Bueno Díez, Marta, Fleitas Pérez, Catherine, de la Fuente, Maricruz, Serrano Casasola, José Carlos Enrique, Granado-Serrano, Ana Belén, Santamaría Gómez, Maite, Yeramian, Nadine, Zorzano-Martínez, Marta, Mora Giral, Concepció, Lecube Torelló, Albert
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/463641
Acceso en línea:https://doi.org/10.3390/nu15102414
https://hdl.handle.net/10459.1/463641
Access Level:acceso abierto
Palabra clave:PKN1
Visceral adipose tissue
Insulin resistance
Type 2 diabetes
Adipocyte
Glucose metabolism
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spelling PKN1 Kinase: A Key Player in Adipocyte Differentiation and Glucose MetabolismHerrerías González, FernandoYeramian Hakim, AndreeBaena-Fustegueras, Juan ABueno Díez, MartaFleitas Pérez, Catherinede la Fuente, MaricruzSerrano Casasola, José Carlos EnriqueGranado-Serrano, Ana BelénSantamaría Gómez, MaiteYeramian, NadineZorzano-Martínez, MartaMora Giral, ConcepcióLecube Torelló, AlbertPKN1Visceral adipose tissueInsulin resistanceType 2 diabetesAdipocyteGlucose metabolismAdipocyte dysfunction is the driver of obesity and correlates with insulin resistance and the onset of type 2 diabetes. Protein kinase N1 (PKN1) is a serine/threonine kinase that has been shown to contribute to Glut4 translocation to the membrane and glucose transport. Here, we evaluated the role of PKN1 in glucose metabolism under insulin-resistant conditions in primary visceral adipose tissue (VAT) from 31 patients with obesity and in murine 3T3-L1 adipocytes. In addition, in vitro studies in human VAT samples and mouse adipocytes were conducted to investigate the role of PKN1 in the adipogenic maturation process and glucose homeostasis control. We show that insulin-resistant adipocytes present a decrease in PKN1 activation levels compared to nondiabetic control counterparts. We further show that PKN1 controls the adipogenesis process and glucose metabolism. PKN1-silenced adipocytes present a decrease in both differentiation process and glucose uptake, with a concomitant decrease in the expression levels of adipogenic markers, such as PPARγ, FABP4, adiponectin and CEBPα. Altogether, these results point to PKN1 as a regulator of key signaling pathways involved in adipocyte differentiation and as an emerging player of adipocyte insulin responsiveness. These findings may provide new therapeutic approaches for the management of insulin resistance in type 2 diabetes.This research was funded by Plan Estratégico de Investigación e Innovación en Salud from the Generalitat de Catalunya, grant number PERIS SLT002/16/000276 and the Instituto de Salud Carlos III (PI18/00964), Fondos FEDER “Una manera de hacer Europa”. C.M. has received funding from Ministerio de industria, Economía y competitividad (Ref.SAF2017-82567-R)MDPI2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.3390/nu15102414https://hdl.handle.net/10459.1/463641reponame:Repositori Obert UdL instname:Universitat de Lleida (UdL)InglésReproducció del document publicat a: https://doi.org/10.3390/nu15102414Nutrients 2023, vol. 15, núm. 10cc-by (c)Authors, 2023Attribution 4.0 Internationalinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/oai:repositori.udl.cat:10459.1/4636412026-06-24T12:42:17Z
dc.title.none.fl_str_mv PKN1 Kinase: A Key Player in Adipocyte Differentiation and Glucose Metabolism
title PKN1 Kinase: A Key Player in Adipocyte Differentiation and Glucose Metabolism
spellingShingle PKN1 Kinase: A Key Player in Adipocyte Differentiation and Glucose Metabolism
Herrerías González, Fernando
PKN1
Visceral adipose tissue
Insulin resistance
Type 2 diabetes
Adipocyte
Glucose metabolism
title_short PKN1 Kinase: A Key Player in Adipocyte Differentiation and Glucose Metabolism
title_full PKN1 Kinase: A Key Player in Adipocyte Differentiation and Glucose Metabolism
title_fullStr PKN1 Kinase: A Key Player in Adipocyte Differentiation and Glucose Metabolism
title_full_unstemmed PKN1 Kinase: A Key Player in Adipocyte Differentiation and Glucose Metabolism
title_sort PKN1 Kinase: A Key Player in Adipocyte Differentiation and Glucose Metabolism
dc.creator.none.fl_str_mv Herrerías González, Fernando
Yeramian Hakim, Andree
Baena-Fustegueras, Juan A
Bueno Díez, Marta
Fleitas Pérez, Catherine
de la Fuente, Maricruz
Serrano Casasola, José Carlos Enrique
Granado-Serrano, Ana Belén
Santamaría Gómez, Maite
Yeramian, Nadine
Zorzano-Martínez, Marta
Mora Giral, Concepció
Lecube Torelló, Albert
author Herrerías González, Fernando
author_facet Herrerías González, Fernando
Yeramian Hakim, Andree
Baena-Fustegueras, Juan A
Bueno Díez, Marta
Fleitas Pérez, Catherine
de la Fuente, Maricruz
Serrano Casasola, José Carlos Enrique
Granado-Serrano, Ana Belén
Santamaría Gómez, Maite
Yeramian, Nadine
Zorzano-Martínez, Marta
Mora Giral, Concepció
Lecube Torelló, Albert
author_role author
author2 Yeramian Hakim, Andree
Baena-Fustegueras, Juan A
Bueno Díez, Marta
Fleitas Pérez, Catherine
de la Fuente, Maricruz
Serrano Casasola, José Carlos Enrique
Granado-Serrano, Ana Belén
Santamaría Gómez, Maite
Yeramian, Nadine
Zorzano-Martínez, Marta
Mora Giral, Concepció
Lecube Torelló, Albert
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PKN1
Visceral adipose tissue
Insulin resistance
Type 2 diabetes
Adipocyte
Glucose metabolism
topic PKN1
Visceral adipose tissue
Insulin resistance
Type 2 diabetes
Adipocyte
Glucose metabolism
description Adipocyte dysfunction is the driver of obesity and correlates with insulin resistance and the onset of type 2 diabetes. Protein kinase N1 (PKN1) is a serine/threonine kinase that has been shown to contribute to Glut4 translocation to the membrane and glucose transport. Here, we evaluated the role of PKN1 in glucose metabolism under insulin-resistant conditions in primary visceral adipose tissue (VAT) from 31 patients with obesity and in murine 3T3-L1 adipocytes. In addition, in vitro studies in human VAT samples and mouse adipocytes were conducted to investigate the role of PKN1 in the adipogenic maturation process and glucose homeostasis control. We show that insulin-resistant adipocytes present a decrease in PKN1 activation levels compared to nondiabetic control counterparts. We further show that PKN1 controls the adipogenesis process and glucose metabolism. PKN1-silenced adipocytes present a decrease in both differentiation process and glucose uptake, with a concomitant decrease in the expression levels of adipogenic markers, such as PPARγ, FABP4, adiponectin and CEBPα. Altogether, these results point to PKN1 as a regulator of key signaling pathways involved in adipocyte differentiation and as an emerging player of adipocyte insulin responsiveness. These findings may provide new therapeutic approaches for the management of insulin resistance in type 2 diabetes.
publishDate 2023
dc.date.none.fl_str_mv 2023
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://doi.org/10.3390/nu15102414
https://hdl.handle.net/10459.1/463641
url https://doi.org/10.3390/nu15102414
https://hdl.handle.net/10459.1/463641
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/nu15102414
Nutrients 2023, vol. 15, núm. 10
dc.rights.none.fl_str_mv cc-by (c)Authors, 2023
Attribution 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
rights_invalid_str_mv cc-by (c)Authors, 2023
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositori Obert UdL
instname:Universitat de Lleida (UdL)
instname_str Universitat de Lleida (UdL)
reponame_str Repositori Obert UdL
collection Repositori Obert UdL
repository.name.fl_str_mv
repository.mail.fl_str_mv
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