CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity

OBJECTIVE: Carnitine palmitoyltransferase 1C (CPT1C) is implicated in central regulation of energy homeostasis. Our aim was to investigate whether CPT1C in the ventromedial nucleus of the hypothalamus (VMH) is involved in the activation of brown adipose tissue (BAT) thermogenesis in the early stages...

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Autores: Rodríguez-Rodríguez, Rosalía, Miralpeix, Cristina, Fosch, Anna, Pozo, Macarena, Calderón Domínguez, María, Perpinyà, Xavier, Vellvehí, Miquel, López, Miguel, Herrero Rodríguez, Laura, Serra i Cucurull, Dolors, Casals i Farré, Núria
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/127893
Acceso en línea:https://hdl.handle.net/2445/127893
Access Level:acceso abierto
Palabra clave:Carnitina palmitoïl-transferasa 1
Hipotàlem
Teixit adipós
Obesitat
Carnitine palmitoyltransferase I
Hypothalamus
Adipose tissues
Obesity
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repository_id_str
spelling CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesityRodríguez-Rodríguez, RosalíaMiralpeix, CristinaFosch, AnnaPozo, MacarenaCalderón Domínguez, MaríaPerpinyà, XavierVellvehí, MiquelLópez, MiguelHerrero Rodríguez, LauraSerra i Cucurull, DolorsCasals i Farré, NúriaCarnitina palmitoïl-transferasa 1HipotàlemTeixit adipósObesitatCarnitine palmitoyltransferase IHypothalamusAdipose tissuesObesityOBJECTIVE: Carnitine palmitoyltransferase 1C (CPT1C) is implicated in central regulation of energy homeostasis. Our aim was to investigate whether CPT1C in the ventromedial nucleus of the hypothalamus (VMH) is involved in the activation of brown adipose tissue (BAT) thermogenesis in the early stages of diet-induced obesity. METHODS: CPT1C KO and wild type (WT) mice were exposed to short-term high-fat (HF) diet feeding or to intracerebroventricular leptin administration and BAT thermogenesis activation was evaluated. Body weight, adiposity, food intake, and leptinemia were also assayed. RESULTS: Under 7 days of HF diet, WT mice showed a maximum activation peak of BAT thermogenesis that counteracted obesity development, whereas this activation was impaired in CPT1C KO mice. KO animals evidenced higher body weight, adiposity, hyperleptinemia, ER stress, and disrupted hypothalamic leptin signaling. Leptin-induced BAT thermogenesis was abolished in KO mice. These results indicate an earlier onset leptin resistance in CPT1C KO mice. Since AMPK in the VMH is crucial in the regulation of BAT thermogenesis, we analyzed if CPT1C was a downstream factor of this pathway. Genetic inactivation of AMPK within the VMH was unable to induce BAT thermogenesis and body weight loss in KO mice, indicating that CPT1C is likely downstream AMPK in the central mechanism modulating thermogenesis within the VMH. Quite opposite, the expression of CPT1C in the VMH restored the phenotype. CONCLUSION: CPT1C is necessary for the activation of BAT thermogenesis driven by leptin, HF diet exposure, and AMPK inhibition within the VMH. This study underscores the importance of CPT1C in the activation of BAT thermogenesis to counteract diet-induced obesity. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved. KEYWORDS: Brown adipose tissue; CPT1C; Diet-induced obesity; Hypothalamus; ThermogenesisElsevier GmbH2019201920182019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion11 p.application/pdfhttps://hdl.handle.net/2445/127893Articles publicats en revistes (Bioquímica i Fisiologia)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1016/j.molmet.2018.10.010Molecular Metabolism, 2018, vol. 2019, num. 19, p. 75-85https://doi.org/10.1016/j.molmet.2018.10.010cc-by-nc-nd (c) Rodríguez-Rodríguez, Rosalía et al., 2018http://creativecommons.org/licenses/by-nc-nd/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1278932026-05-29T05:05:01Z
dc.title.none.fl_str_mv CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
title CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
spellingShingle CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
Rodríguez-Rodríguez, Rosalía
Carnitina palmitoïl-transferasa 1
Hipotàlem
Teixit adipós
Obesitat
Carnitine palmitoyltransferase I
Hypothalamus
Adipose tissues
Obesity
title_short CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
title_full CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
title_fullStr CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
title_full_unstemmed CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
title_sort CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
dc.creator.none.fl_str_mv Rodríguez-Rodríguez, Rosalía
Miralpeix, Cristina
Fosch, Anna
Pozo, Macarena
Calderón Domínguez, María
Perpinyà, Xavier
Vellvehí, Miquel
López, Miguel
Herrero Rodríguez, Laura
Serra i Cucurull, Dolors
Casals i Farré, Núria
author Rodríguez-Rodríguez, Rosalía
author_facet Rodríguez-Rodríguez, Rosalía
Miralpeix, Cristina
Fosch, Anna
Pozo, Macarena
Calderón Domínguez, María
Perpinyà, Xavier
Vellvehí, Miquel
López, Miguel
Herrero Rodríguez, Laura
Serra i Cucurull, Dolors
Casals i Farré, Núria
author_role author
author2 Miralpeix, Cristina
Fosch, Anna
Pozo, Macarena
Calderón Domínguez, María
Perpinyà, Xavier
Vellvehí, Miquel
López, Miguel
Herrero Rodríguez, Laura
Serra i Cucurull, Dolors
Casals i Farré, Núria
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Carnitina palmitoïl-transferasa 1
Hipotàlem
Teixit adipós
Obesitat
Carnitine palmitoyltransferase I
Hypothalamus
Adipose tissues
Obesity
topic Carnitina palmitoïl-transferasa 1
Hipotàlem
Teixit adipós
Obesitat
Carnitine palmitoyltransferase I
Hypothalamus
Adipose tissues
Obesity
description OBJECTIVE: Carnitine palmitoyltransferase 1C (CPT1C) is implicated in central regulation of energy homeostasis. Our aim was to investigate whether CPT1C in the ventromedial nucleus of the hypothalamus (VMH) is involved in the activation of brown adipose tissue (BAT) thermogenesis in the early stages of diet-induced obesity. METHODS: CPT1C KO and wild type (WT) mice were exposed to short-term high-fat (HF) diet feeding or to intracerebroventricular leptin administration and BAT thermogenesis activation was evaluated. Body weight, adiposity, food intake, and leptinemia were also assayed. RESULTS: Under 7 days of HF diet, WT mice showed a maximum activation peak of BAT thermogenesis that counteracted obesity development, whereas this activation was impaired in CPT1C KO mice. KO animals evidenced higher body weight, adiposity, hyperleptinemia, ER stress, and disrupted hypothalamic leptin signaling. Leptin-induced BAT thermogenesis was abolished in KO mice. These results indicate an earlier onset leptin resistance in CPT1C KO mice. Since AMPK in the VMH is crucial in the regulation of BAT thermogenesis, we analyzed if CPT1C was a downstream factor of this pathway. Genetic inactivation of AMPK within the VMH was unable to induce BAT thermogenesis and body weight loss in KO mice, indicating that CPT1C is likely downstream AMPK in the central mechanism modulating thermogenesis within the VMH. Quite opposite, the expression of CPT1C in the VMH restored the phenotype. CONCLUSION: CPT1C is necessary for the activation of BAT thermogenesis driven by leptin, HF diet exposure, and AMPK inhibition within the VMH. This study underscores the importance of CPT1C in the activation of BAT thermogenesis to counteract diet-induced obesity. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved. KEYWORDS: Brown adipose tissue; CPT1C; Diet-induced obesity; Hypothalamus; Thermogenesis
publishDate 2018
dc.date.none.fl_str_mv 2018
2019
2019
2019
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/2445/127893
url https://hdl.handle.net/2445/127893
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.molmet.2018.10.010
Molecular Metabolism, 2018, vol. 2019, num. 19, p. 75-85
https://doi.org/10.1016/j.molmet.2018.10.010
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Rodríguez-Rodríguez, Rosalía et al., 2018
http://creativecommons.org/licenses/by-nc-nd/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Rodríguez-Rodríguez, Rosalía et al., 2018
http://creativecommons.org/licenses/by-nc-nd/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 11 p.
application/pdf
dc.publisher.none.fl_str_mv Elsevier GmbH
publisher.none.fl_str_mv Elsevier GmbH
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Fisiologia)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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