Maternal overweight induced by a diet with high content of saturated fat activates placental mTOR and eIF2α signaling and increases fetal growth in rats.

Autores
Gaccioli, Francesca; White, Verónica; Capobianco, Evangelina Lorena; Powwel, Theresa L.; Jawerbaum, Alicia Sandra; Jansson, Thomas
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The mammalian target of rapamycin (mTOR) and the eukaryotic initiation factor 2 (eIF2) signaling pathways control protein synthesis in response to nutrient availability. Moreover mTOR is a positive regulator of placental nutrient transport and is involved in the regulation of fetal growth. We hypothesized that maternal overweight, induced by a diet with high saturated fat content: i) up-regulates placental mTOR activity and nutrient transport resulting in fetal overgrowth; ii) inhibits phosphorylation of eIF2 at its alpha subunit (eIF2alpha) and iii) leads to placental inflammation. Albino Wistar female rats were fed a control or high saturated fat (HF) diet for 7 weeks before mating and during pregnancy. At Gestational Day 21 the HF diet significantly increased maternal and fetal triglyceride, leptin and insulin (but not glucose) levels, maternal and fetal weights, and placental weights trended to increase. Phosphorylated 4EBP1 (T37/46 and S65) was significantly higher and phosphorylated rpS6 (S235/236) trended to increase in the placentas of dams fed a HF diet, indicating an activation of mTOR Complex 1 (mTORC1). Phosphorylation of AMPK and eIF2alpha was reduced in the HF diet group compared to the control. The expression and activity of placental nutrient transporters and lipoprotein lipase (LPL), as well as the activation of inflammatory pathways were not altered by the maternal diet. We conclude that maternal overweight induced by a HF diet stimulates mTORC1 activity and decreases eIF2alpha phosphorylation in rat placentas. We speculate that these changes may up-regulate protein synthesis and contribute to placental and fetal overgrowth.
Fil: Gaccioli, Francesca. Center For Pregnancy And Newborn Research; Estados Unidos
Fil: White, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Capobianco, Evangelina Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Powwel, Theresa L.. Center For Pregnancy And Newborn Research; Estados Unidos
Fil: Jawerbaum, Alicia Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Jansson, Thomas. Center For Pregnancy And Newborn Research; Estados Unidos
Materia
Pregnancy
Placental Inflammation
Placental Transport
Fetal Overgrowth
Maternal Obesity
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/8520
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/8520
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Maternal overweight induced by a diet with high content of saturated fat activates placental mTOR and eIF2α signaling and increases fetal growth in rats.Gaccioli, FrancescaWhite, VerónicaCapobianco, Evangelina LorenaPowwel, Theresa L.Jawerbaum, Alicia SandraJansson, ThomasPregnancyPlacental InflammationPlacental TransportFetal OvergrowthMaternal Obesityhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The mammalian target of rapamycin (mTOR) and the eukaryotic initiation factor 2 (eIF2) signaling pathways control protein synthesis in response to nutrient availability. Moreover mTOR is a positive regulator of placental nutrient transport and is involved in the regulation of fetal growth. We hypothesized that maternal overweight, induced by a diet with high saturated fat content: i) up-regulates placental mTOR activity and nutrient transport resulting in fetal overgrowth; ii) inhibits phosphorylation of eIF2 at its alpha subunit (eIF2alpha) and iii) leads to placental inflammation. Albino Wistar female rats were fed a control or high saturated fat (HF) diet for 7 weeks before mating and during pregnancy. At Gestational Day 21 the HF diet significantly increased maternal and fetal triglyceride, leptin and insulin (but not glucose) levels, maternal and fetal weights, and placental weights trended to increase. Phosphorylated 4EBP1 (T37/46 and S65) was significantly higher and phosphorylated rpS6 (S235/236) trended to increase in the placentas of dams fed a HF diet, indicating an activation of mTOR Complex 1 (mTORC1). Phosphorylation of AMPK and eIF2alpha was reduced in the HF diet group compared to the control. The expression and activity of placental nutrient transporters and lipoprotein lipase (LPL), as well as the activation of inflammatory pathways were not altered by the maternal diet. We conclude that maternal overweight induced by a HF diet stimulates mTORC1 activity and decreases eIF2alpha phosphorylation in rat placentas. We speculate that these changes may up-regulate protein synthesis and contribute to placental and fetal overgrowth.Fil: Gaccioli, Francesca. Center For Pregnancy And Newborn Research; Estados UnidosFil: White, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Capobianco, Evangelina Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Powwel, Theresa L.. Center For Pregnancy And Newborn Research; Estados UnidosFil: Jawerbaum, Alicia Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Jansson, Thomas. Center For Pregnancy And Newborn Research; Estados UnidosSociety For The Study Of Reproduction2013-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/8520Gaccioli, Francesca; White, Verónica; Capobianco, Evangelina Lorena; Powwel, Theresa L.; Jawerbaum, Alicia Sandra; et al.; Maternal overweight induced by a diet with high content of saturated fat activates placental mTOR and eIF2α signaling and increases fetal growth in rats.; Society For The Study Of Reproduction; Biology Of Reproduction; 89; 4; 9-2013; 1-110006-3363enginfo:eu-repo/semantics/altIdentifier/url/http://www.biolreprod.org/content/89/4/96.longinfo:eu-repo/semantics/altIdentifier/doi/10.1095/​biolreprod.113.109702info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:15:22Zoai:ri.conicet.gov.ar:11336/8520instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:15:22.768CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Maternal overweight induced by a diet with high content of saturated fat activates placental mTOR and eIF2α signaling and increases fetal growth in rats.
title Maternal overweight induced by a diet with high content of saturated fat activates placental mTOR and eIF2α signaling and increases fetal growth in rats.
spellingShingle Maternal overweight induced by a diet with high content of saturated fat activates placental mTOR and eIF2α signaling and increases fetal growth in rats.
Gaccioli, Francesca
Pregnancy
Placental Inflammation
Placental Transport
Fetal Overgrowth
Maternal Obesity
title_short Maternal overweight induced by a diet with high content of saturated fat activates placental mTOR and eIF2α signaling and increases fetal growth in rats.
title_full Maternal overweight induced by a diet with high content of saturated fat activates placental mTOR and eIF2α signaling and increases fetal growth in rats.
title_fullStr Maternal overweight induced by a diet with high content of saturated fat activates placental mTOR and eIF2α signaling and increases fetal growth in rats.
title_full_unstemmed Maternal overweight induced by a diet with high content of saturated fat activates placental mTOR and eIF2α signaling and increases fetal growth in rats.
title_sort Maternal overweight induced by a diet with high content of saturated fat activates placental mTOR and eIF2α signaling and increases fetal growth in rats.
dc.creator.none.fl_str_mv Gaccioli, Francesca
White, Verónica
Capobianco, Evangelina Lorena
Powwel, Theresa L.
Jawerbaum, Alicia Sandra
Jansson, Thomas
author Gaccioli, Francesca
author_facet Gaccioli, Francesca
White, Verónica
Capobianco, Evangelina Lorena
Powwel, Theresa L.
Jawerbaum, Alicia Sandra
Jansson, Thomas
author_role author
author2 White, Verónica
Capobianco, Evangelina Lorena
Powwel, Theresa L.
Jawerbaum, Alicia Sandra
Jansson, Thomas
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Pregnancy
Placental Inflammation
Placental Transport
Fetal Overgrowth
Maternal Obesity
topic Pregnancy
Placental Inflammation
Placental Transport
Fetal Overgrowth
Maternal Obesity
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The mammalian target of rapamycin (mTOR) and the eukaryotic initiation factor 2 (eIF2) signaling pathways control protein synthesis in response to nutrient availability. Moreover mTOR is a positive regulator of placental nutrient transport and is involved in the regulation of fetal growth. We hypothesized that maternal overweight, induced by a diet with high saturated fat content: i) up-regulates placental mTOR activity and nutrient transport resulting in fetal overgrowth; ii) inhibits phosphorylation of eIF2 at its alpha subunit (eIF2alpha) and iii) leads to placental inflammation. Albino Wistar female rats were fed a control or high saturated fat (HF) diet for 7 weeks before mating and during pregnancy. At Gestational Day 21 the HF diet significantly increased maternal and fetal triglyceride, leptin and insulin (but not glucose) levels, maternal and fetal weights, and placental weights trended to increase. Phosphorylated 4EBP1 (T37/46 and S65) was significantly higher and phosphorylated rpS6 (S235/236) trended to increase in the placentas of dams fed a HF diet, indicating an activation of mTOR Complex 1 (mTORC1). Phosphorylation of AMPK and eIF2alpha was reduced in the HF diet group compared to the control. The expression and activity of placental nutrient transporters and lipoprotein lipase (LPL), as well as the activation of inflammatory pathways were not altered by the maternal diet. We conclude that maternal overweight induced by a HF diet stimulates mTORC1 activity and decreases eIF2alpha phosphorylation in rat placentas. We speculate that these changes may up-regulate protein synthesis and contribute to placental and fetal overgrowth.
Fil: Gaccioli, Francesca. Center For Pregnancy And Newborn Research; Estados Unidos
Fil: White, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Capobianco, Evangelina Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Powwel, Theresa L.. Center For Pregnancy And Newborn Research; Estados Unidos
Fil: Jawerbaum, Alicia Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Jansson, Thomas. Center For Pregnancy And Newborn Research; Estados Unidos
description The mammalian target of rapamycin (mTOR) and the eukaryotic initiation factor 2 (eIF2) signaling pathways control protein synthesis in response to nutrient availability. Moreover mTOR is a positive regulator of placental nutrient transport and is involved in the regulation of fetal growth. We hypothesized that maternal overweight, induced by a diet with high saturated fat content: i) up-regulates placental mTOR activity and nutrient transport resulting in fetal overgrowth; ii) inhibits phosphorylation of eIF2 at its alpha subunit (eIF2alpha) and iii) leads to placental inflammation. Albino Wistar female rats were fed a control or high saturated fat (HF) diet for 7 weeks before mating and during pregnancy. At Gestational Day 21 the HF diet significantly increased maternal and fetal triglyceride, leptin and insulin (but not glucose) levels, maternal and fetal weights, and placental weights trended to increase. Phosphorylated 4EBP1 (T37/46 and S65) was significantly higher and phosphorylated rpS6 (S235/236) trended to increase in the placentas of dams fed a HF diet, indicating an activation of mTOR Complex 1 (mTORC1). Phosphorylation of AMPK and eIF2alpha was reduced in the HF diet group compared to the control. The expression and activity of placental nutrient transporters and lipoprotein lipase (LPL), as well as the activation of inflammatory pathways were not altered by the maternal diet. We conclude that maternal overweight induced by a HF diet stimulates mTORC1 activity and decreases eIF2alpha phosphorylation in rat placentas. We speculate that these changes may up-regulate protein synthesis and contribute to placental and fetal overgrowth.
publishDate 2013
dc.date.none.fl_str_mv 2013-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/8520
Gaccioli, Francesca; White, Verónica; Capobianco, Evangelina Lorena; Powwel, Theresa L.; Jawerbaum, Alicia Sandra; et al.; Maternal overweight induced by a diet with high content of saturated fat activates placental mTOR and eIF2α signaling and increases fetal growth in rats.; Society For The Study Of Reproduction; Biology Of Reproduction; 89; 4; 9-2013; 1-11
0006-3363
url http://hdl.handle.net/11336/8520
identifier_str_mv Gaccioli, Francesca; White, Verónica; Capobianco, Evangelina Lorena; Powwel, Theresa L.; Jawerbaum, Alicia Sandra; et al.; Maternal overweight induced by a diet with high content of saturated fat activates placental mTOR and eIF2α signaling and increases fetal growth in rats.; Society For The Study Of Reproduction; Biology Of Reproduction; 89; 4; 9-2013; 1-11
0006-3363
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.biolreprod.org/content/89/4/96.long
info:eu-repo/semantics/altIdentifier/doi/10.1095/​biolreprod.113.109702
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Society For The Study Of Reproduction
publisher.none.fl_str_mv Society For The Study Of Reproduction
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.993085

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