Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice

Soler Vázquez, M. Carmen; Romero Romero, María del Mar; Todorčević, Marijana; Delgado, Katia; Calatayud Aristoy, Carles; Benítez Amaro, Aleyda; La Chica Lhoëst, Maria Teresa; Mera Nanín, Paula; Zagmutt Caroxa, Sebastián; Bastías-Pérez, Marianela; Ibeas, Kevin; Casals, Núria; Escolà Gil, Joan Carles; Llorente Cortés, Vicenta; Consiglio, Antonella; Serra i Cucurull, Dolors; Herrero Rodríguez, Laura

Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice

Obesity and its associated metabolic comorbidities are a rising global health and social issue, with novel therapeutic approaches urgently needed. Adipose tissue plays a key role in the regulation of energy balance and adipose tissue-derived mesenchymal stem cells (AT-MSCs) have gained great interes...

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Autores:	Soler Vázquez, M. Carmen, Romero Romero, María del Mar, Todorčević, Marijana, Delgado, Katia, Calatayud Aristoy, Carles, Benítez Amaro, Aleyda, La Chica Lhoëst, Maria Teresa, Mera Nanín, Paula, Zagmutt Caroxa, Sebastián, Bastías-Pérez, Marianela, Ibeas, Kevin, Casals, Núria, Escolà Gil, Joan Carles, Llorente Cortés, Vicenta, Consiglio, Antonella, Serra i Cucurull, Dolors, Herrero Rodríguez, Laura
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2023
País:	España
Institución:	Universidad de Barcelona
Repositorio:	Dipòsit Digital de la UB
OAI Identifier:	oai:diposit.ub.edu:2445/201162
Acceso en línea:	https://hdl.handle.net/2445/201162
Access Level:	acceso abierto
Palabra clave:	Obesitat Teixit adipós Inflamació Glucosa Ratolins (Animals de laboratori) Obesity Adipose tissues Inflammation Glucose Mice (Laboratory animals)

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spelling	Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in miceSoler Vázquez, M. CarmenRomero Romero, María del MarTodorčević, MarijanaDelgado, KatiaCalatayud Aristoy, CarlesBenítez Amaro, AleydaLa Chica Lhoëst, Maria TeresaMera Nanín, PaulaZagmutt Caroxa, SebastiánBastías-Pérez, MarianelaIbeas, KevinCasals, NúriaEscolà Gil, Joan CarlesLlorente Cortés, VicentaConsiglio, AntonellaSerra i Cucurull, DolorsHerrero Rodríguez, LauraObesitatTeixit adipósInflamacióGlucosaRatolins (Animals de laboratori)ObesityAdipose tissuesInflammationGlucoseMice (Laboratory animals)Obesity and its associated metabolic comorbidities are a rising global health and social issue, with novel therapeutic approaches urgently needed. Adipose tissue plays a key role in the regulation of energy balance and adipose tissue-derived mesenchymal stem cells (AT-MSCs) have gained great interest in cell therapy. Carnitine palmitoyltransferase 1A (CPT1A) is the gatekeeper enzyme for mitochondrial fatty acid oxidation. Here, we aimed to generate adipocytes expressing a constitutively active CPT1A form (CPT1AM) that can improve the obese phenotype in mice after their implantation. AT-MSCs were differentiated into mature adipocytes, subjected to lentivirus-mediated expression of CPT1AM or the GFP control, and subcutaneously implanted into mice fed a high-fat diet (HFD). CPT1AM-implanted mice showed lower body weight, hepatic steatosis and serum insulin and cholesterol levels alongside improved glucose tolerance. HFD-induced increases in adipose tissue hypertrophy, fibrosis, inflammation, endoplasmic reticulum stress and apoptosis were reduced in CPT1AM-implanted mice. In addition, the expression of mitochondrial respiratory chain complexes was enhanced in the adipose tissue of CPT1AM-implanted mice. Our results demonstrate that implantation of CPT1AM-expressing AT-MSC-derived adipocytes into HFD-fed mice improves the obese metabolic phenotype, supporting the future clinical use of this ex vivo gene therapy approach.Elsevier2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/201162Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.ymben.2023.04.010Metabolic Engineering, 2023, vol. 77, p. 256-272https://doi.org/10.1016/j.ymben.2023.04.010cc-by-nc-nd (c) Soler-Vázquez, M. Carmen et al., 2023https://creativecommons.org/licenses/by-nc-nd/4.0/https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2011622026-05-27T06:46:51Z
dc.title.none.fl_str_mv	Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice
title	Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice
spellingShingle	Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice Soler Vázquez, M. Carmen Obesitat Teixit adipós Inflamació Glucosa Ratolins (Animals de laboratori) Obesity Adipose tissues Inflammation Glucose Mice (Laboratory animals)
title_short	Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice
title_full	Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice
title_fullStr	Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice
title_full_unstemmed	Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice
title_sort	Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice
dc.creator.none.fl_str_mv	Soler Vázquez, M. Carmen Romero Romero, María del Mar Todorčević, Marijana Delgado, Katia Calatayud Aristoy, Carles Benítez Amaro, Aleyda La Chica Lhoëst, Maria Teresa Mera Nanín, Paula Zagmutt Caroxa, Sebastián Bastías-Pérez, Marianela Ibeas, Kevin Casals, Núria Escolà Gil, Joan Carles Llorente Cortés, Vicenta Consiglio, Antonella Serra i Cucurull, Dolors Herrero Rodríguez, Laura
author	Soler Vázquez, M. Carmen
author_facet	Soler Vázquez, M. Carmen Romero Romero, María del Mar Todorčević, Marijana Delgado, Katia Calatayud Aristoy, Carles Benítez Amaro, Aleyda La Chica Lhoëst, Maria Teresa Mera Nanín, Paula Zagmutt Caroxa, Sebastián Bastías-Pérez, Marianela Ibeas, Kevin Casals, Núria Escolà Gil, Joan Carles Llorente Cortés, Vicenta Consiglio, Antonella Serra i Cucurull, Dolors Herrero Rodríguez, Laura
author_role	author
author2	Romero Romero, María del Mar Todorčević, Marijana Delgado, Katia Calatayud Aristoy, Carles Benítez Amaro, Aleyda La Chica Lhoëst, Maria Teresa Mera Nanín, Paula Zagmutt Caroxa, Sebastián Bastías-Pérez, Marianela Ibeas, Kevin Casals, Núria Escolà Gil, Joan Carles Llorente Cortés, Vicenta Consiglio, Antonella Serra i Cucurull, Dolors Herrero Rodríguez, Laura
author2_role	author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Obesitat Teixit adipós Inflamació Glucosa Ratolins (Animals de laboratori) Obesity Adipose tissues Inflammation Glucose Mice (Laboratory animals)
topic	Obesitat Teixit adipós Inflamació Glucosa Ratolins (Animals de laboratori) Obesity Adipose tissues Inflammation Glucose Mice (Laboratory animals)
description	Obesity and its associated metabolic comorbidities are a rising global health and social issue, with novel therapeutic approaches urgently needed. Adipose tissue plays a key role in the regulation of energy balance and adipose tissue-derived mesenchymal stem cells (AT-MSCs) have gained great interest in cell therapy. Carnitine palmitoyltransferase 1A (CPT1A) is the gatekeeper enzyme for mitochondrial fatty acid oxidation. Here, we aimed to generate adipocytes expressing a constitutively active CPT1A form (CPT1AM) that can improve the obese phenotype in mice after their implantation. AT-MSCs were differentiated into mature adipocytes, subjected to lentivirus-mediated expression of CPT1AM or the GFP control, and subcutaneously implanted into mice fed a high-fat diet (HFD). CPT1AM-implanted mice showed lower body weight, hepatic steatosis and serum insulin and cholesterol levels alongside improved glucose tolerance. HFD-induced increases in adipose tissue hypertrophy, fibrosis, inflammation, endoplasmic reticulum stress and apoptosis were reduced in CPT1AM-implanted mice. In addition, the expression of mitochondrial respiratory chain complexes was enhanced in the adipose tissue of CPT1AM-implanted mice. Our results demonstrate that implantation of CPT1AM-expressing AT-MSC-derived adipocytes into HFD-fed mice improves the obese metabolic phenotype, supporting the future clinical use of this ex vivo gene therapy approach.
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://hdl.handle.net/2445/201162
url	https://hdl.handle.net/2445/201162
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/10.1016/j.ymben.2023.04.010 Metabolic Engineering, 2023, vol. 77, p. 256-272 https://doi.org/10.1016/j.ymben.2023.04.010
dc.rights.none.fl_str_mv	cc-by-nc-nd (c) Soler-Vázquez, M. Carmen et al., 2023 https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc-by-nc-nd (c) Soler-Vázquez, M. Carmen et al., 2023 https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Elsevier
publisher.none.fl_str_mv	Elsevier
dc.source.none.fl_str_mv	Articles publicats en revistes (Patologia i Terapèutica Experimental) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona
instname_str	Universidad de Barcelona
reponame_str	Dipòsit Digital de la UB
collection	Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice

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