Compounds that modulate AMPK activity and hepatic steatosis impact the biosynthesis of microRNAs required to maintain lipid homeostasis in hepatocytes

Background While the impact of metformin in hepatocytes leads to fatty acid (FA) oxidation and decreased lipogenesis, hepatic microRNAs (miRNAs) have been associated with fat overload and impaired metabolism, contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Methods We i...

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Autores: Latorre Luque, Jèssica, Ortega, Francisco, Liñares Pose, Laura, Moreno Navarrete, José María, Lluch Balaña, Aina, Comas Vila, Ferran, Oliveras-Cañellas, Núria, Ricart, Wifredo, Höring, Marcus, Zhou, You, Liebisch, Gerhard, Haridas, P.A. Nidhina, Olkkonen, Vesa M., López, Miguel, Fernández-Real Lemos, José Manuel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/19182
Acceso en línea:http://hdl.handle.net/10256/19182
Access Level:acceso abierto
Palabra clave:MicroARN
MicroRNA
Cèl·lules hepàtiques
Liver cells
Homeòstasi
Homeostasis
Esteatosi hepàtica
Fatty liver
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spelling Compounds that modulate AMPK activity and hepatic steatosis impact the biosynthesis of microRNAs required to maintain lipid homeostasis in hepatocytesLatorre Luque, JèssicaOrtega, FranciscoLiñares Pose, LauraMoreno Navarrete, José MaríaLluch Balaña, AinaComas Vila, FerranOliveras-Cañellas, NúriaRicart, WifredoHöring, MarcusZhou, YouLiebisch, GerhardHaridas, P.A. NidhinaOlkkonen, Vesa M.López, MiguelFernández-Real Lemos, José ManuelMicroARNMicroRNACèl·lules hepàtiquesLiver cellsHomeòstasiHomeostasisEsteatosi hepàticaFatty liverBackground While the impact of metformin in hepatocytes leads to fatty acid (FA) oxidation and decreased lipogenesis, hepatic microRNAs (miRNAs) have been associated with fat overload and impaired metabolism, contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Methods We investigated the expression of hundreds of miRNAs in primary hepatocytes challenged by compounds modulating steatosis, palmitic acid and compound C (as inducers), and metformin (as an inhibitor). Then, additional hepatocyte and rodent models were evaluated, together with transient mimic miRNAs transfection, lipid droplet staining, thin-layer chromatography, quantitative lipidomes, and mitochondrial activity, while human samples outlined the translational significance of this work. Findings Our results show that treatments triggering fat accumulation and AMPK disruption may compromise the biosynthesis of hepatic miRNAs, while the knockdown of the miRNA-processing enzyme DICER in human hepatocytes exhibited increased lipid deposition. In this context, the ectopic recovery of miR-30b and miR-30c led to significant changes in genes related to FA metabolism, consistent reduction of ceramides, higher mitochondrial activity, and enabled β-oxidation, redirecting FA metabolism from energy storage to expenditure. Interpretation Current findings unravel the biosynthesis of hepatic miR-30b and miR-30c in tackling inadequate FA accumulation, offering a potential avenue for the treatment of NAFLD.Instituto de Salud Carlos III (ISCIII), Govern de la Generalitat (PERIS2016), Associació Catalana de Diabetis (ACD), Sociedad Española de Diabetes (SED), Fondo Europeo de Desarrollo Regional (FEDER), Xunta de Galicia, Ministerio de Economía y Competitividad (MINECO), “La Caixa” Foundation, and CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN).Elsevier2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionpeer-reviewedapplication/pdfhttp://hdl.handle.net/10256/19182EBioMedicine, 2020, vol. 53, art.núm. 102697Articles publicats (IdIBGi)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ebiom.2020.102697info:eu-repo/semantics/altIdentifier/issn/2352-3964Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10256/191822026-05-29T05:05:01Z
dc.title.none.fl_str_mv Compounds that modulate AMPK activity and hepatic steatosis impact the biosynthesis of microRNAs required to maintain lipid homeostasis in hepatocytes
title Compounds that modulate AMPK activity and hepatic steatosis impact the biosynthesis of microRNAs required to maintain lipid homeostasis in hepatocytes
spellingShingle Compounds that modulate AMPK activity and hepatic steatosis impact the biosynthesis of microRNAs required to maintain lipid homeostasis in hepatocytes
Latorre Luque, Jèssica
MicroARN
MicroRNA
Cèl·lules hepàtiques
Liver cells
Homeòstasi
Homeostasis
Esteatosi hepàtica
Fatty liver
title_short Compounds that modulate AMPK activity and hepatic steatosis impact the biosynthesis of microRNAs required to maintain lipid homeostasis in hepatocytes
title_full Compounds that modulate AMPK activity and hepatic steatosis impact the biosynthesis of microRNAs required to maintain lipid homeostasis in hepatocytes
title_fullStr Compounds that modulate AMPK activity and hepatic steatosis impact the biosynthesis of microRNAs required to maintain lipid homeostasis in hepatocytes
title_full_unstemmed Compounds that modulate AMPK activity and hepatic steatosis impact the biosynthesis of microRNAs required to maintain lipid homeostasis in hepatocytes
title_sort Compounds that modulate AMPK activity and hepatic steatosis impact the biosynthesis of microRNAs required to maintain lipid homeostasis in hepatocytes
dc.creator.none.fl_str_mv Latorre Luque, Jèssica
Ortega, Francisco
Liñares Pose, Laura
Moreno Navarrete, José María
Lluch Balaña, Aina
Comas Vila, Ferran
Oliveras-Cañellas, Núria
Ricart, Wifredo
Höring, Marcus
Zhou, You
Liebisch, Gerhard
Haridas, P.A. Nidhina
Olkkonen, Vesa M.
López, Miguel
Fernández-Real Lemos, José Manuel
author Latorre Luque, Jèssica
author_facet Latorre Luque, Jèssica
Ortega, Francisco
Liñares Pose, Laura
Moreno Navarrete, José María
Lluch Balaña, Aina
Comas Vila, Ferran
Oliveras-Cañellas, Núria
Ricart, Wifredo
Höring, Marcus
Zhou, You
Liebisch, Gerhard
Haridas, P.A. Nidhina
Olkkonen, Vesa M.
López, Miguel
Fernández-Real Lemos, José Manuel
author_role author
author2 Ortega, Francisco
Liñares Pose, Laura
Moreno Navarrete, José María
Lluch Balaña, Aina
Comas Vila, Ferran
Oliveras-Cañellas, Núria
Ricart, Wifredo
Höring, Marcus
Zhou, You
Liebisch, Gerhard
Haridas, P.A. Nidhina
Olkkonen, Vesa M.
López, Miguel
Fernández-Real Lemos, José Manuel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv MicroARN
MicroRNA
Cèl·lules hepàtiques
Liver cells
Homeòstasi
Homeostasis
Esteatosi hepàtica
Fatty liver
topic MicroARN
MicroRNA
Cèl·lules hepàtiques
Liver cells
Homeòstasi
Homeostasis
Esteatosi hepàtica
Fatty liver
description Background While the impact of metformin in hepatocytes leads to fatty acid (FA) oxidation and decreased lipogenesis, hepatic microRNAs (miRNAs) have been associated with fat overload and impaired metabolism, contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Methods We investigated the expression of hundreds of miRNAs in primary hepatocytes challenged by compounds modulating steatosis, palmitic acid and compound C (as inducers), and metformin (as an inhibitor). Then, additional hepatocyte and rodent models were evaluated, together with transient mimic miRNAs transfection, lipid droplet staining, thin-layer chromatography, quantitative lipidomes, and mitochondrial activity, while human samples outlined the translational significance of this work. Findings Our results show that treatments triggering fat accumulation and AMPK disruption may compromise the biosynthesis of hepatic miRNAs, while the knockdown of the miRNA-processing enzyme DICER in human hepatocytes exhibited increased lipid deposition. In this context, the ectopic recovery of miR-30b and miR-30c led to significant changes in genes related to FA metabolism, consistent reduction of ceramides, higher mitochondrial activity, and enabled β-oxidation, redirecting FA metabolism from energy storage to expenditure. Interpretation Current findings unravel the biosynthesis of hepatic miR-30b and miR-30c in tackling inadequate FA accumulation, offering a potential avenue for the treatment of NAFLD.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
peer-reviewed
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10256/19182
url http://hdl.handle.net/10256/19182
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ebiom.2020.102697
info:eu-repo/semantics/altIdentifier/issn/2352-3964
dc.rights.none.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv EBioMedicine, 2020, vol. 53, art.núm. 102697
Articles publicats (IdIBGi)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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