Defective liver glycogen autophagy related to hyperinsulinemia in intrauterine growth-restricted newborn wistar rats

Maternal malnutrition plays a critical role in the developmental programming of later metabolic diseases susceptibility in the offspring, such as obesity and type 2 diabetes. Because the liver is the major organ that produces and supplies blood glucose, we aimed at defining the potential role of liv...

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Autores: Toro-Martín, Juan de, Fernández Marcelo, Tamara, González-Rodríguez, Águeda, Escrivá, Fernando, Valverde, Ángela M., Álvarez Escolá, Carmen, Fernández Millán, Elisa
Formato: artículo
Fecha de publicación:2020
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/128440
Acesso em linha:https://hdl.handle.net/20.500.14352/128440
Access Level:acceso abierto
Palavra-chave:577.1
577.2
Biología molecular (Farmacia)
Bioquímica (Farmacia)
2415 Biología Molecular
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spelling Defective liver glycogen autophagy related to hyperinsulinemia in intrauterine growth-restricted newborn wistar ratsToro-Martín, Juan deFernández Marcelo, TamaraGonzález-Rodríguez, ÁguedaEscrivá, FernandoValverde, Ángela M.Álvarez Escolá, CarmenFernández Millán, Elisa577.1577.2Biología molecular (Farmacia)Bioquímica (Farmacia)2415 Biología MolecularMaternal malnutrition plays a critical role in the developmental programming of later metabolic diseases susceptibility in the offspring, such as obesity and type 2 diabetes. Because the liver is the major organ that produces and supplies blood glucose, we aimed at defining the potential role of liver glycogen autophagy in the programming of glucose metabolism disturbances. To this end, newborns were obtained from pregnant Wistar rats fed ad libitum with a standard diet or 65% food-restricted during the last week of gestation. We found that newborns from undernourished mothers showed markedly high basal insulin levels whereas those of glucagon were decreased. This unbalance led to activation of the mTORC1 pathway and inhibition of hepatic autophagy compromising the adequate handling of glycogen in the very early hours of extrauterine life. Restoration of autophagy with rapamycin but not with glucagon, indicated no defect in autophagy machinery per se, but in signals triggered by glucagon. Taken together, these results support the notion that hyperinsulinemia is an important mechanism by which mobilization of liver glycogen by autophagy is defective in food-restricted animals. This early alteration in the hormonal control of liver glycogen autophagy may influence the risk of developing metabolic diseases later in life.Nature Publishing GroupUniversidad Complutense de Madrid20202020-10-1920202020-10-19journal articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/128440reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1284402026-06-02T12:44:21Z
dc.title.none.fl_str_mv Defective liver glycogen autophagy related to hyperinsulinemia in intrauterine growth-restricted newborn wistar rats
title Defective liver glycogen autophagy related to hyperinsulinemia in intrauterine growth-restricted newborn wistar rats
spellingShingle Defective liver glycogen autophagy related to hyperinsulinemia in intrauterine growth-restricted newborn wistar rats
Toro-Martín, Juan de
577.1
577.2
Biología molecular (Farmacia)
Bioquímica (Farmacia)
2415 Biología Molecular
title_short Defective liver glycogen autophagy related to hyperinsulinemia in intrauterine growth-restricted newborn wistar rats
title_full Defective liver glycogen autophagy related to hyperinsulinemia in intrauterine growth-restricted newborn wistar rats
title_fullStr Defective liver glycogen autophagy related to hyperinsulinemia in intrauterine growth-restricted newborn wistar rats
title_full_unstemmed Defective liver glycogen autophagy related to hyperinsulinemia in intrauterine growth-restricted newborn wistar rats
title_sort Defective liver glycogen autophagy related to hyperinsulinemia in intrauterine growth-restricted newborn wistar rats
dc.creator.none.fl_str_mv Toro-Martín, Juan de
Fernández Marcelo, Tamara
González-Rodríguez, Águeda
Escrivá, Fernando
Valverde, Ángela M.
Álvarez Escolá, Carmen
Fernández Millán, Elisa
author Toro-Martín, Juan de
author_facet Toro-Martín, Juan de
Fernández Marcelo, Tamara
González-Rodríguez, Águeda
Escrivá, Fernando
Valverde, Ángela M.
Álvarez Escolá, Carmen
Fernández Millán, Elisa
author_role author
author2 Fernández Marcelo, Tamara
González-Rodríguez, Águeda
Escrivá, Fernando
Valverde, Ángela M.
Álvarez Escolá, Carmen
Fernández Millán, Elisa
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 577.1
577.2
Biología molecular (Farmacia)
Bioquímica (Farmacia)
2415 Biología Molecular
topic 577.1
577.2
Biología molecular (Farmacia)
Bioquímica (Farmacia)
2415 Biología Molecular
description Maternal malnutrition plays a critical role in the developmental programming of later metabolic diseases susceptibility in the offspring, such as obesity and type 2 diabetes. Because the liver is the major organ that produces and supplies blood glucose, we aimed at defining the potential role of liver glycogen autophagy in the programming of glucose metabolism disturbances. To this end, newborns were obtained from pregnant Wistar rats fed ad libitum with a standard diet or 65% food-restricted during the last week of gestation. We found that newborns from undernourished mothers showed markedly high basal insulin levels whereas those of glucagon were decreased. This unbalance led to activation of the mTORC1 pathway and inhibition of hepatic autophagy compromising the adequate handling of glycogen in the very early hours of extrauterine life. Restoration of autophagy with rapamycin but not with glucagon, indicated no defect in autophagy machinery per se, but in signals triggered by glucagon. Taken together, these results support the notion that hyperinsulinemia is an important mechanism by which mobilization of liver glycogen by autophagy is defective in food-restricted animals. This early alteration in the hormonal control of liver glycogen autophagy may influence the risk of developing metabolic diseases later in life.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-10-19
2020
2020-10-19
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/128440
url https://hdl.handle.net/20.500.14352/128440
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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