MicroRNA Let-7 targets AMPK and impairs hepatic lipid metabolism in offspring of maternal obese pregnancies

Abstract Nutritional status during gestation may lead to a phenomenon known as metabolic programming, which can be triggered by epigenetic mechanisms. The Let-7 family of microRNAs were one of the first to be discovered, and are closely related to metabolic processes. Bioinformatic analysis revealed...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Laís A. P. Simino, Carolina Panzarin, Marina F. Fontana, Thais de Fante, Murilo V. Geraldo, Letícia M. Ignácio-Souza, Marciane Milanski, Marcio A. Torsoni, Michael G. Ross, Mina Desai, Adriana S. Torsoni
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
Materias:
R
Q
Acceso en línea:https://doaj.org/article/0f68b0c64c594985bf206d39b2e7bd90
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:0f68b0c64c594985bf206d39b2e7bd90
record_format dspace
spelling oai:doaj.org-article:0f68b0c64c594985bf206d39b2e7bd902021-12-02T17:39:19ZMicroRNA Let-7 targets AMPK and impairs hepatic lipid metabolism in offspring of maternal obese pregnancies10.1038/s41598-021-88518-82045-2322https://doaj.org/article/0f68b0c64c594985bf206d39b2e7bd902021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88518-8https://doaj.org/toc/2045-2322Abstract Nutritional status during gestation may lead to a phenomenon known as metabolic programming, which can be triggered by epigenetic mechanisms. The Let-7 family of microRNAs were one of the first to be discovered, and are closely related to metabolic processes. Bioinformatic analysis revealed that Prkaa2, the gene that encodes AMPK α2, is a predicted target of Let-7. Here we aimed to investigate whether Let-7 has a role in AMPKα2 levels in the NAFLD development in the offspring programmed by maternal obesity. Let-7 levels were upregulated in the liver of newborn mice from obese dams, while the levels of Prkaa2 were downregulated. Let-7 levels strongly correlated with serum glucose, insulin and NEFA, and in vitro treatment of AML12 with glucose and NEFA lead to higher Let-7 expression. Transfection of Let-7a mimic lead to downregulation of AMPKα2 levels, while the transfection with Let-7a inhibitor impaired both NEFA-mediated reduction of Prkaa2 levels and the fat accumulation driven by NEFA. The transfection of Let-7a inhibitor in ex-vivo liver slices from the offspring of obese dams restored phospho-AMPKα2 levels. In summary, Let-7a appears to regulate hepatic AMPKα2 protein levels and lead to the early hepatic metabolic disturbances in the offspring of obese dams.Laís A. P. SiminoCarolina PanzarinMarina F. FontanaThais de FanteMurilo V. GeraldoLetícia M. Ignácio-SouzaMarciane MilanskiMarcio A. TorsoniMichael G. RossMina DesaiAdriana S. TorsoniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Laís A. P. Simino
Carolina Panzarin
Marina F. Fontana
Thais de Fante
Murilo V. Geraldo
Letícia M. Ignácio-Souza
Marciane Milanski
Marcio A. Torsoni
Michael G. Ross
Mina Desai
Adriana S. Torsoni
MicroRNA Let-7 targets AMPK and impairs hepatic lipid metabolism in offspring of maternal obese pregnancies
description Abstract Nutritional status during gestation may lead to a phenomenon known as metabolic programming, which can be triggered by epigenetic mechanisms. The Let-7 family of microRNAs were one of the first to be discovered, and are closely related to metabolic processes. Bioinformatic analysis revealed that Prkaa2, the gene that encodes AMPK α2, is a predicted target of Let-7. Here we aimed to investigate whether Let-7 has a role in AMPKα2 levels in the NAFLD development in the offspring programmed by maternal obesity. Let-7 levels were upregulated in the liver of newborn mice from obese dams, while the levels of Prkaa2 were downregulated. Let-7 levels strongly correlated with serum glucose, insulin and NEFA, and in vitro treatment of AML12 with glucose and NEFA lead to higher Let-7 expression. Transfection of Let-7a mimic lead to downregulation of AMPKα2 levels, while the transfection with Let-7a inhibitor impaired both NEFA-mediated reduction of Prkaa2 levels and the fat accumulation driven by NEFA. The transfection of Let-7a inhibitor in ex-vivo liver slices from the offspring of obese dams restored phospho-AMPKα2 levels. In summary, Let-7a appears to regulate hepatic AMPKα2 protein levels and lead to the early hepatic metabolic disturbances in the offspring of obese dams.
format article
author Laís A. P. Simino
Carolina Panzarin
Marina F. Fontana
Thais de Fante
Murilo V. Geraldo
Letícia M. Ignácio-Souza
Marciane Milanski
Marcio A. Torsoni
Michael G. Ross
Mina Desai
Adriana S. Torsoni
author_facet Laís A. P. Simino
Carolina Panzarin
Marina F. Fontana
Thais de Fante
Murilo V. Geraldo
Letícia M. Ignácio-Souza
Marciane Milanski
Marcio A. Torsoni
Michael G. Ross
Mina Desai
Adriana S. Torsoni
author_sort Laís A. P. Simino
title MicroRNA Let-7 targets AMPK and impairs hepatic lipid metabolism in offspring of maternal obese pregnancies
title_short MicroRNA Let-7 targets AMPK and impairs hepatic lipid metabolism in offspring of maternal obese pregnancies
title_full MicroRNA Let-7 targets AMPK and impairs hepatic lipid metabolism in offspring of maternal obese pregnancies
title_fullStr MicroRNA Let-7 targets AMPK and impairs hepatic lipid metabolism in offspring of maternal obese pregnancies
title_full_unstemmed MicroRNA Let-7 targets AMPK and impairs hepatic lipid metabolism in offspring of maternal obese pregnancies
title_sort microrna let-7 targets ampk and impairs hepatic lipid metabolism in offspring of maternal obese pregnancies
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/0f68b0c64c594985bf206d39b2e7bd90
work_keys_str_mv AT laisapsimino micrornalet7targetsampkandimpairshepaticlipidmetabolisminoffspringofmaternalobesepregnancies
AT carolinapanzarin micrornalet7targetsampkandimpairshepaticlipidmetabolisminoffspringofmaternalobesepregnancies
AT marinaffontana micrornalet7targetsampkandimpairshepaticlipidmetabolisminoffspringofmaternalobesepregnancies
AT thaisdefante micrornalet7targetsampkandimpairshepaticlipidmetabolisminoffspringofmaternalobesepregnancies
AT murilovgeraldo micrornalet7targetsampkandimpairshepaticlipidmetabolisminoffspringofmaternalobesepregnancies
AT leticiamignaciosouza micrornalet7targetsampkandimpairshepaticlipidmetabolisminoffspringofmaternalobesepregnancies
AT marcianemilanski micrornalet7targetsampkandimpairshepaticlipidmetabolisminoffspringofmaternalobesepregnancies
AT marcioatorsoni micrornalet7targetsampkandimpairshepaticlipidmetabolisminoffspringofmaternalobesepregnancies
AT michaelgross micrornalet7targetsampkandimpairshepaticlipidmetabolisminoffspringofmaternalobesepregnancies
AT minadesai micrornalet7targetsampkandimpairshepaticlipidmetabolisminoffspringofmaternalobesepregnancies
AT adrianastorsoni micrornalet7targetsampkandimpairshepaticlipidmetabolisminoffspringofmaternalobesepregnancies
_version_ 1718379808437567488