Insulin signalling regulates fatty acid catabolisme at the level of CoA activation

The insulin/IGF signaling pathway is a highly conserved regulator of metabolism in flies and mammals, regulating multiple physiological functions including lipid metabolism. Although insulin signaling is known to regulate the activity of a number of enzymes in metabolic pathways, a comprehensive und...

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Detalhes bibliográficos
Autores: Xu, Xiaojun, Gopalacharyullu, Peddinti, Seppänen-Laakso, Tuulikki, Ruskeepaa, Anna-Liisa, Aye, Cho-Cho, Carson, Brian P., Mora Fayos, Sílvia, Oresic, Matej, Teleman, Aurelio A.
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2012
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/176797
Acesso em linha:https://hdl.handle.net/2445/176797
Access Level:Acceso aberto
Palavra-chave:Insulina
Teixit adipós
Insulin
Adipose tissues
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spelling Insulin signalling regulates fatty acid catabolisme at the level of CoA activationXu, XiaojunGopalacharyullu, PeddintiSeppänen-Laakso, TuulikkiRuskeepaa, Anna-LiisaAye, Cho-ChoCarson, Brian P.Mora Fayos, SílviaOresic, MatejTeleman, Aurelio A.InsulinaTeixit adipósInsulinAdipose tissuesThe insulin/IGF signaling pathway is a highly conserved regulator of metabolism in flies and mammals, regulating multiple physiological functions including lipid metabolism. Although insulin signaling is known to regulate the activity of a number of enzymes in metabolic pathways, a comprehensive understanding of how the insulin signaling pathway regulates metabolic pathways is still lacking. Accepted knowledge suggests the key regulated step in triglyceride (TAG) catabolism is the release of fatty acids from TAG via the action of lipases. We show here that an additional, important regulated step is the activation of fatty acids for beta-oxidation via Acyl Co-A synthetases (ACS). We identify pudgy as an ACS that is transcriptionally regulated by direct FOXO action in Drosophila. Increasing or reducing pudgy expression in vivo causes a decrease or increase in organismal TAG levels respectively, indicating that pudgy expression levels are important for proper lipid homeostasis. We show that multiple ACSs are also transcriptionally regulated by insulin signaling in mammalian cells. In sum, we identify fatty acid activation onto CoA as an important, regulated step in triglyceride catabolism, and we identify a mechanistic link through which insulin regulates lipid homeostasis.Public Library of Science (PLoS)2021202120122021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion14 p.application/pdfhttps://hdl.handle.net/2445/176797Articles publicats en revistes (Bioquímica i Biomedicina Molecular)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/10.1371/journal.pgen.1002478PLoS Genetics, 2012, vol. 8, p. e1002478https://doi.org/10.1371/journal.pgen.1002478info:eu-repo/grantAgreement/EC/FP7/223450cc-by (c) Xu, Xiaojun et al., 2012http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1767972026-05-29T05:05:01Z
dc.title.none.fl_str_mv Insulin signalling regulates fatty acid catabolisme at the level of CoA activation
title Insulin signalling regulates fatty acid catabolisme at the level of CoA activation
spellingShingle Insulin signalling regulates fatty acid catabolisme at the level of CoA activation
Xu, Xiaojun
Insulina
Teixit adipós
Insulin
Adipose tissues
title_short Insulin signalling regulates fatty acid catabolisme at the level of CoA activation
title_full Insulin signalling regulates fatty acid catabolisme at the level of CoA activation
title_fullStr Insulin signalling regulates fatty acid catabolisme at the level of CoA activation
title_full_unstemmed Insulin signalling regulates fatty acid catabolisme at the level of CoA activation
title_sort Insulin signalling regulates fatty acid catabolisme at the level of CoA activation
dc.creator.none.fl_str_mv Xu, Xiaojun
Gopalacharyullu, Peddinti
Seppänen-Laakso, Tuulikki
Ruskeepaa, Anna-Liisa
Aye, Cho-Cho
Carson, Brian P.
Mora Fayos, Sílvia
Oresic, Matej
Teleman, Aurelio A.
author Xu, Xiaojun
author_facet Xu, Xiaojun
Gopalacharyullu, Peddinti
Seppänen-Laakso, Tuulikki
Ruskeepaa, Anna-Liisa
Aye, Cho-Cho
Carson, Brian P.
Mora Fayos, Sílvia
Oresic, Matej
Teleman, Aurelio A.
author_role author
author2 Gopalacharyullu, Peddinti
Seppänen-Laakso, Tuulikki
Ruskeepaa, Anna-Liisa
Aye, Cho-Cho
Carson, Brian P.
Mora Fayos, Sílvia
Oresic, Matej
Teleman, Aurelio A.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Insulina
Teixit adipós
Insulin
Adipose tissues
topic Insulina
Teixit adipós
Insulin
Adipose tissues
description The insulin/IGF signaling pathway is a highly conserved regulator of metabolism in flies and mammals, regulating multiple physiological functions including lipid metabolism. Although insulin signaling is known to regulate the activity of a number of enzymes in metabolic pathways, a comprehensive understanding of how the insulin signaling pathway regulates metabolic pathways is still lacking. Accepted knowledge suggests the key regulated step in triglyceride (TAG) catabolism is the release of fatty acids from TAG via the action of lipases. We show here that an additional, important regulated step is the activation of fatty acids for beta-oxidation via Acyl Co-A synthetases (ACS). We identify pudgy as an ACS that is transcriptionally regulated by direct FOXO action in Drosophila. Increasing or reducing pudgy expression in vivo causes a decrease or increase in organismal TAG levels respectively, indicating that pudgy expression levels are important for proper lipid homeostasis. We show that multiple ACSs are also transcriptionally regulated by insulin signaling in mammalian cells. In sum, we identify fatty acid activation onto CoA as an important, regulated step in triglyceride catabolism, and we identify a mechanistic link through which insulin regulates lipid homeostasis.
publishDate 2012
dc.date.none.fl_str_mv 2012
2021
2021
2021
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/2445/176797
url https://hdl.handle.net/2445/176797
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/10.1371/journal.pgen.1002478
PLoS Genetics, 2012, vol. 8, p. e1002478
https://doi.org/10.1371/journal.pgen.1002478
info:eu-repo/grantAgreement/EC/FP7/223450
dc.rights.none.fl_str_mv cc-by (c) Xu, Xiaojun et al., 2012
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Xu, Xiaojun et al., 2012
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 14 p.
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
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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