Hypothalamic ceramide levels regulated by CPT1C mediate the orexigenic effect of ghrelin.

Recent data suggest that ghrelin exerts its orexigenic action through regulation of hypothalamic AMP-activated protein kinase (AMPK) pathway, leading to a decline in malonyl-CoA levels and desinhibition of carnitine palmitoyltransferase 1A (CPT1A), which increases mitochondrial fatty acid oxidation...

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Autores: Ramírez, Sara, Matins, Luis, Jacas, Jordi, Carrasco, Patricia, Pozo, Macarena, Clotet Erra, Josep, Serra i Cucurull, Dolors, Hegardt, Fausto, Diéguez, Carlos, López, Miguel, Casals i Farré, Núria
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
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:2445/165007
Acceso en línea:https://hdl.handle.net/2445/165007
Access Level:acceso abierto
Palabra clave:Carnitina palmitoïl-transferasa 1
Metabolisme
Farmacocinètica
Farmacologia
Fisiologia
Carnitine palmitoyltransferase I
Metabolism
Pharmacokinetics
Pharmacology
Physiology
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spelling Hypothalamic ceramide levels regulated by CPT1C mediate the orexigenic effect of ghrelin.Ramírez, SaraMatins, LuisJacas, JordiCarrasco, PatriciaPozo, MacarenaClotet Erra, JosepSerra i Cucurull, DolorsHegardt, FaustoDiéguez, CarlosLópez, MiguelCasals i Farré, NúriaCarnitina palmitoïl-transferasa 1MetabolismeFarmacocinèticaFarmacologiaFisiologiaCarnitine palmitoyltransferase IMetabolismPharmacokineticsPharmacologyPhysiologyRecent data suggest that ghrelin exerts its orexigenic action through regulation of hypothalamic AMP-activated protein kinase (AMPK) pathway, leading to a decline in malonyl-CoA levels and desinhibition of carnitine palmitoyltransferase 1A (CPT1A), which increases mitochondrial fatty acid oxidation and ultimately enhances the expression of the orexigenic neuropeptides agouti-related protein (AgRP) and neuropeptide Y (NPY). However, it is unclear whether the brain-specific isoform CPT1C, which is located in the endoplasmic reticulum (ER) of neurons, may play a role on this action. Here, we demonstrate that ghrelin's orexigenic action is totally blunted in CPT1C knock-out (KO) mice, despite having the canonical ghrelin signaling pathway activated. We also demonstrate that ghrelin elicits a marked upregulation of hypothalamic C18:0-ceramide levels mediated by CPT1C. Notably, central inhibition of ceramide synthesis with myriocin negated ghrelin's orexigenic action and normalized the levels of AgRP and NPY, as well as their key transcription factors pCREB and FoxO1. Finally, central treatment with ceramide induced food intake and orexigenic neuropeptides expression in CPT1C KO mice. Overall, these data indicate that, in addition to formerly reported mechanisms, ghrelin also induces food intake through regulation of hypothalamic CPT1C and ceramide metabolism, a finding of potential importance for the understanding and treatment of obesity.American Diabetes Association2020202020132020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion9 p.application/pdfhttps://hdl.handle.net/2445/165007Articles 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/10.2337/db12-1451Diabetes, 2013, vol. 62, num. 7, p. 2329-2337https://doi.org/10.2337/db12-1451info:eu-repo/grantAgreement/EC/FP7/281854cc-by-nc-nd (c) American Diabetes Association, 2013http://creativecommons.org/licenses/by-nc-nd/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1650072026-05-29T05:05:01Z
dc.title.none.fl_str_mv Hypothalamic ceramide levels regulated by CPT1C mediate the orexigenic effect of ghrelin.
title Hypothalamic ceramide levels regulated by CPT1C mediate the orexigenic effect of ghrelin.
spellingShingle Hypothalamic ceramide levels regulated by CPT1C mediate the orexigenic effect of ghrelin.
Ramírez, Sara
Carnitina palmitoïl-transferasa 1
Metabolisme
Farmacocinètica
Farmacologia
Fisiologia
Carnitine palmitoyltransferase I
Metabolism
Pharmacokinetics
Pharmacology
Physiology
title_short Hypothalamic ceramide levels regulated by CPT1C mediate the orexigenic effect of ghrelin.
title_full Hypothalamic ceramide levels regulated by CPT1C mediate the orexigenic effect of ghrelin.
title_fullStr Hypothalamic ceramide levels regulated by CPT1C mediate the orexigenic effect of ghrelin.
title_full_unstemmed Hypothalamic ceramide levels regulated by CPT1C mediate the orexigenic effect of ghrelin.
title_sort Hypothalamic ceramide levels regulated by CPT1C mediate the orexigenic effect of ghrelin.
dc.creator.none.fl_str_mv Ramírez, Sara
Matins, Luis
Jacas, Jordi
Carrasco, Patricia
Pozo, Macarena
Clotet Erra, Josep
Serra i Cucurull, Dolors
Hegardt, Fausto
Diéguez, Carlos
López, Miguel
Casals i Farré, Núria
author Ramírez, Sara
author_facet Ramírez, Sara
Matins, Luis
Jacas, Jordi
Carrasco, Patricia
Pozo, Macarena
Clotet Erra, Josep
Serra i Cucurull, Dolors
Hegardt, Fausto
Diéguez, Carlos
López, Miguel
Casals i Farré, Núria
author_role author
author2 Matins, Luis
Jacas, Jordi
Carrasco, Patricia
Pozo, Macarena
Clotet Erra, Josep
Serra i Cucurull, Dolors
Hegardt, Fausto
Diéguez, Carlos
López, Miguel
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
Metabolisme
Farmacocinètica
Farmacologia
Fisiologia
Carnitine palmitoyltransferase I
Metabolism
Pharmacokinetics
Pharmacology
Physiology
topic Carnitina palmitoïl-transferasa 1
Metabolisme
Farmacocinètica
Farmacologia
Fisiologia
Carnitine palmitoyltransferase I
Metabolism
Pharmacokinetics
Pharmacology
Physiology
description Recent data suggest that ghrelin exerts its orexigenic action through regulation of hypothalamic AMP-activated protein kinase (AMPK) pathway, leading to a decline in malonyl-CoA levels and desinhibition of carnitine palmitoyltransferase 1A (CPT1A), which increases mitochondrial fatty acid oxidation and ultimately enhances the expression of the orexigenic neuropeptides agouti-related protein (AgRP) and neuropeptide Y (NPY). However, it is unclear whether the brain-specific isoform CPT1C, which is located in the endoplasmic reticulum (ER) of neurons, may play a role on this action. Here, we demonstrate that ghrelin's orexigenic action is totally blunted in CPT1C knock-out (KO) mice, despite having the canonical ghrelin signaling pathway activated. We also demonstrate that ghrelin elicits a marked upregulation of hypothalamic C18:0-ceramide levels mediated by CPT1C. Notably, central inhibition of ceramide synthesis with myriocin negated ghrelin's orexigenic action and normalized the levels of AgRP and NPY, as well as their key transcription factors pCREB and FoxO1. Finally, central treatment with ceramide induced food intake and orexigenic neuropeptides expression in CPT1C KO mice. Overall, these data indicate that, in addition to formerly reported mechanisms, ghrelin also induces food intake through regulation of hypothalamic CPT1C and ceramide metabolism, a finding of potential importance for the understanding and treatment of obesity.
publishDate 2013
dc.date.none.fl_str_mv 2013
2020
2020
2020
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/2445/165007
url https://hdl.handle.net/2445/165007
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/10.2337/db12-1451
Diabetes, 2013, vol. 62, num. 7, p. 2329-2337
https://doi.org/10.2337/db12-1451
info:eu-repo/grantAgreement/EC/FP7/281854
dc.rights.none.fl_str_mv cc-by-nc-nd (c) American Diabetes Association, 2013
http://creativecommons.org/licenses/by-nc-nd/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) American Diabetes Association, 2013
http://creativecommons.org/licenses/by-nc-nd/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 9 p.
application/pdf
dc.publisher.none.fl_str_mv American Diabetes Association
publisher.none.fl_str_mv American Diabetes Association
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 15.228081

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