Liver X receptor-α activation enhances cholesterol secretion in lactating mammary epithelium
- Autores
- Grinman, Diego Yair; Careaga Quiroga, Valeria Pilar; Wellberg, Elizabeth A.; Dansey, Maria Virginia; Kordon, Edith Claudia; Anderson, Steven M.; Maier, Marta Silvia; Burton, Gerardo; MacLean, Paul S.; Rudolph, Michael C.; Pecci, Adali
- Año de publicación
- 2019
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Liver X receptors (LXRs) are li-gand-dependent transcription factors activated by cholesterol metabolites. These receptors induce a suite of target genes required for de novo synthesis of triglycerides and cholesterol transport in many tissues. Two different isoforms, LXRβ and LXRβ, have been well characterized in liver, adipocytes, macrophages, and intestinal epithelium among others, but their contribution to cholesterol and fatty acid efflux in the lactating mammary epithelium is poorly understood. We hypothesize that LXR regulates lipogenesis during milk fat production in lactation. Global mRNA analysis of mouse mammary epithelial cells (MECs) revealed multiple LXR/RXR targets upregulated sharply early in lactation compared with midpregnancy. LXRβ is the primary isoform, and its protein levels increase throughout lactation in MECs. The LXR agonist GW3965 markedly induced several genes involved in cholesterol transport and lipogenesis and enhanced cytoplasmic lipid droplet accumulation in the HC11 MEC cell line. Importantly, in vivo pharmacological activation of LXR increased the milk cholesterol percentage and induced sterol regulatory element-binding protein 1c (Srebp1c) and ATP-binding cassette transporter a7 (Abca7) expression in MECs. Cumulatively, our findings identify LXRβ as an important regulator of cholesterol incorporation into the milk through key nodes of de novo lipogenesis, suggesting a potential therapeutic target in women with difficulty initiating lactation.
Fil: Grinman, Diego Yair. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Careaga Quiroga, Valeria Pilar. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Wellberg, Elizabeth A.. University of Colorado; Estados Unidos
Fil: Dansey, Maria Virginia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Kordon, Edith Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Anderson, Steven M.. University of Colorado; Estados Unidos
Fil: Maier, Marta Silvia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Burton, Gerardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: MacLean, Paul S.. University of Colorado; Estados Unidos
Fil: Rudolph, Michael C.. University of Colorado; Estados Unidos
Fil: Pecci, Adali. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina - Materia
-
CHOLESTEROL PATHWAY
LACTATION
LXR
MAMMARY EPITHELIAL CELLS
MILK LIPID - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/121039
Ver los metadatos del registro completo
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Liver X receptor-α activation enhances cholesterol secretion in lactating mammary epitheliumGrinman, Diego YairCareaga Quiroga, Valeria PilarWellberg, Elizabeth A.Dansey, Maria VirginiaKordon, Edith ClaudiaAnderson, Steven M.Maier, Marta SilviaBurton, GerardoMacLean, Paul S.Rudolph, Michael C.Pecci, AdaliCHOLESTEROL PATHWAYLACTATIONLXRMAMMARY EPITHELIAL CELLSMILK LIPIDhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Liver X receptors (LXRs) are li-gand-dependent transcription factors activated by cholesterol metabolites. These receptors induce a suite of target genes required for de novo synthesis of triglycerides and cholesterol transport in many tissues. Two different isoforms, LXRβ and LXRβ, have been well characterized in liver, adipocytes, macrophages, and intestinal epithelium among others, but their contribution to cholesterol and fatty acid efflux in the lactating mammary epithelium is poorly understood. We hypothesize that LXR regulates lipogenesis during milk fat production in lactation. Global mRNA analysis of mouse mammary epithelial cells (MECs) revealed multiple LXR/RXR targets upregulated sharply early in lactation compared with midpregnancy. LXRβ is the primary isoform, and its protein levels increase throughout lactation in MECs. The LXR agonist GW3965 markedly induced several genes involved in cholesterol transport and lipogenesis and enhanced cytoplasmic lipid droplet accumulation in the HC11 MEC cell line. Importantly, in vivo pharmacological activation of LXR increased the milk cholesterol percentage and induced sterol regulatory element-binding protein 1c (Srebp1c) and ATP-binding cassette transporter a7 (Abca7) expression in MECs. Cumulatively, our findings identify LXRβ as an important regulator of cholesterol incorporation into the milk through key nodes of de novo lipogenesis, suggesting a potential therapeutic target in women with difficulty initiating lactation.Fil: Grinman, Diego Yair. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Careaga Quiroga, Valeria Pilar. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wellberg, Elizabeth A.. University of Colorado; Estados UnidosFil: Dansey, Maria Virginia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kordon, Edith Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Anderson, Steven M.. University of Colorado; Estados UnidosFil: Maier, Marta Silvia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Burton, Gerardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: MacLean, Paul S.. University of Colorado; Estados UnidosFil: Rudolph, Michael C.. University of Colorado; Estados UnidosFil: Pecci, Adali. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaAmerican Physiological Society2019-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/121039Grinman, Diego Yair; Careaga Quiroga, Valeria Pilar; Wellberg, Elizabeth A.; Dansey, Maria Virginia; Kordon, Edith Claudia; et al.; Liver X receptor-α activation enhances cholesterol secretion in lactating mammary epithelium; American Physiological Society; American Journal Of Physiology-endocrinology And Metabolism; 316; 6; 6-2019; E1136-E11450193-1849CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/10.1152/ajpendo.00548.2018info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpendo.00548.2018info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:36:29Zoai:ri.conicet.gov.ar:11336/121039instacron: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:34982025-09-29 10:36:29.695CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Liver X receptor-α activation enhances cholesterol secretion in lactating mammary epithelium |
title |
Liver X receptor-α activation enhances cholesterol secretion in lactating mammary epithelium |
spellingShingle |
Liver X receptor-α activation enhances cholesterol secretion in lactating mammary epithelium Grinman, Diego Yair CHOLESTEROL PATHWAY LACTATION LXR MAMMARY EPITHELIAL CELLS MILK LIPID |
title_short |
Liver X receptor-α activation enhances cholesterol secretion in lactating mammary epithelium |
title_full |
Liver X receptor-α activation enhances cholesterol secretion in lactating mammary epithelium |
title_fullStr |
Liver X receptor-α activation enhances cholesterol secretion in lactating mammary epithelium |
title_full_unstemmed |
Liver X receptor-α activation enhances cholesterol secretion in lactating mammary epithelium |
title_sort |
Liver X receptor-α activation enhances cholesterol secretion in lactating mammary epithelium |
dc.creator.none.fl_str_mv |
Grinman, Diego Yair Careaga Quiroga, Valeria Pilar Wellberg, Elizabeth A. Dansey, Maria Virginia Kordon, Edith Claudia Anderson, Steven M. Maier, Marta Silvia Burton, Gerardo MacLean, Paul S. Rudolph, Michael C. Pecci, Adali |
author |
Grinman, Diego Yair |
author_facet |
Grinman, Diego Yair Careaga Quiroga, Valeria Pilar Wellberg, Elizabeth A. Dansey, Maria Virginia Kordon, Edith Claudia Anderson, Steven M. Maier, Marta Silvia Burton, Gerardo MacLean, Paul S. Rudolph, Michael C. Pecci, Adali |
author_role |
author |
author2 |
Careaga Quiroga, Valeria Pilar Wellberg, Elizabeth A. Dansey, Maria Virginia Kordon, Edith Claudia Anderson, Steven M. Maier, Marta Silvia Burton, Gerardo MacLean, Paul S. Rudolph, Michael C. Pecci, Adali |
author2_role |
author author author author author author author author author author |
dc.subject.none.fl_str_mv |
CHOLESTEROL PATHWAY LACTATION LXR MAMMARY EPITHELIAL CELLS MILK LIPID |
topic |
CHOLESTEROL PATHWAY LACTATION LXR MAMMARY EPITHELIAL CELLS MILK LIPID |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Liver X receptors (LXRs) are li-gand-dependent transcription factors activated by cholesterol metabolites. These receptors induce a suite of target genes required for de novo synthesis of triglycerides and cholesterol transport in many tissues. Two different isoforms, LXRβ and LXRβ, have been well characterized in liver, adipocytes, macrophages, and intestinal epithelium among others, but their contribution to cholesterol and fatty acid efflux in the lactating mammary epithelium is poorly understood. We hypothesize that LXR regulates lipogenesis during milk fat production in lactation. Global mRNA analysis of mouse mammary epithelial cells (MECs) revealed multiple LXR/RXR targets upregulated sharply early in lactation compared with midpregnancy. LXRβ is the primary isoform, and its protein levels increase throughout lactation in MECs. The LXR agonist GW3965 markedly induced several genes involved in cholesterol transport and lipogenesis and enhanced cytoplasmic lipid droplet accumulation in the HC11 MEC cell line. Importantly, in vivo pharmacological activation of LXR increased the milk cholesterol percentage and induced sterol regulatory element-binding protein 1c (Srebp1c) and ATP-binding cassette transporter a7 (Abca7) expression in MECs. Cumulatively, our findings identify LXRβ as an important regulator of cholesterol incorporation into the milk through key nodes of de novo lipogenesis, suggesting a potential therapeutic target in women with difficulty initiating lactation. Fil: Grinman, Diego Yair. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina Fil: Careaga Quiroga, Valeria Pilar. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Wellberg, Elizabeth A.. University of Colorado; Estados Unidos Fil: Dansey, Maria Virginia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Kordon, Edith Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina Fil: Anderson, Steven M.. University of Colorado; Estados Unidos Fil: Maier, Marta Silvia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Burton, Gerardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: MacLean, Paul S.. University of Colorado; Estados Unidos Fil: Rudolph, Michael C.. University of Colorado; Estados Unidos Fil: Pecci, Adali. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina |
description |
Liver X receptors (LXRs) are li-gand-dependent transcription factors activated by cholesterol metabolites. These receptors induce a suite of target genes required for de novo synthesis of triglycerides and cholesterol transport in many tissues. Two different isoforms, LXRβ and LXRβ, have been well characterized in liver, adipocytes, macrophages, and intestinal epithelium among others, but their contribution to cholesterol and fatty acid efflux in the lactating mammary epithelium is poorly understood. We hypothesize that LXR regulates lipogenesis during milk fat production in lactation. Global mRNA analysis of mouse mammary epithelial cells (MECs) revealed multiple LXR/RXR targets upregulated sharply early in lactation compared with midpregnancy. LXRβ is the primary isoform, and its protein levels increase throughout lactation in MECs. The LXR agonist GW3965 markedly induced several genes involved in cholesterol transport and lipogenesis and enhanced cytoplasmic lipid droplet accumulation in the HC11 MEC cell line. Importantly, in vivo pharmacological activation of LXR increased the milk cholesterol percentage and induced sterol regulatory element-binding protein 1c (Srebp1c) and ATP-binding cassette transporter a7 (Abca7) expression in MECs. Cumulatively, our findings identify LXRβ as an important regulator of cholesterol incorporation into the milk through key nodes of de novo lipogenesis, suggesting a potential therapeutic target in women with difficulty initiating lactation. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-06 |
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/11336/121039 Grinman, Diego Yair; Careaga Quiroga, Valeria Pilar; Wellberg, Elizabeth A.; Dansey, Maria Virginia; Kordon, Edith Claudia; et al.; Liver X receptor-α activation enhances cholesterol secretion in lactating mammary epithelium; American Physiological Society; American Journal Of Physiology-endocrinology And Metabolism; 316; 6; 6-2019; E1136-E1145 0193-1849 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/121039 |
identifier_str_mv |
Grinman, Diego Yair; Careaga Quiroga, Valeria Pilar; Wellberg, Elizabeth A.; Dansey, Maria Virginia; Kordon, Edith Claudia; et al.; Liver X receptor-α activation enhances cholesterol secretion in lactating mammary epithelium; American Physiological Society; American Journal Of Physiology-endocrinology And Metabolism; 316; 6; 6-2019; E1136-E1145 0193-1849 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/10.1152/ajpendo.00548.2018 info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpendo.00548.2018 |
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 application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
American Physiological Society |
publisher.none.fl_str_mv |
American Physiological Society |
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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1844614385682612224 |
score |
13.070432 |