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...

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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:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0f68b0c64c594985bf206d39b2e7bd90
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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
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MicroRNA Let-7 targets AMPK and impairs hepatic lipid metabolism in offspring of maternal obese pregnancies

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