ChREBP-driven DNL and PNPLA3 expression induced by liquid fructose are essential in the production of fatty liver and hypertriglyceridemia in a high-fat diet-fed rat model

Scope: The aim of this study is to delineate the contribution of dietary saturated fatty acids (FA) versus liquid fructose to fatty liver and hypertriglyceridemia. Methods and results: Three groups of female rats are maintained for 3 months in standard chow (CT); High-fat diet (46.9% of fat-derived...

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Autores: Velázquez, Ana Magdalena, Bentanachs, Roger, Sala Vila, Aleix, Lázaro, Iolanda, Rodríguez-Morató, Jose, 1987-, Sánchez, Rosa María, Alegret i Jordà, Marta, Roglans i Ribas, Núria, Laguna, Juan Carlos
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/54334
Acceso en línea:http://hdl.handle.net/10230/54334
http://dx.doi.org/10.1002/mnfr.202101115
Access Level:acceso abierto
Palabra clave:NAFLD
Ceramides
Diacylglycerols
Fatty acid β-oxidation
Lipidomics
Liver steatosis
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spelling ChREBP-driven DNL and PNPLA3 expression induced by liquid fructose are essential in the production of fatty liver and hypertriglyceridemia in a high-fat diet-fed rat modelVelázquez, Ana MagdalenaBentanachs, RogerSala Vila, AleixLázaro, IolandaRodríguez-Morató, Jose, 1987-Sánchez, Rosa MaríaAlegret i Jordà, MartaRoglans i Ribas, NúriaLaguna, Juan CarlosNAFLDCeramidesDiacylglycerolsFatty acid β-oxidationLipidomicsLiver steatosisScope: The aim of this study is to delineate the contribution of dietary saturated fatty acids (FA) versus liquid fructose to fatty liver and hypertriglyceridemia. Methods and results: Three groups of female rats are maintained for 3 months in standard chow (CT); High-fat diet (46.9% of fat-derived calories, rich in palmitic and stearic FA, HFD); and HFD with 10% w/v fructose in drinking water (HFHFr). Zoometric parameters, plasma biochemistry, and liver Oil-Red O (ORO) staining, lipidomics, and expression of proteins involved in FA metabolism are analyzed. Both diets increase ingested calories without modifying body weight. Only the HFHFr diet increases liver triglycerides (x11.0), with hypertriglyceridemia (x1.7) and reduces FA β-oxidation (x0.7), and increases liver FA markers of DNL (de novo lipogenesis). Whereas HFD livers show a high content of ceramides, HFHFr samples show unchanged ceramides, and an increase in diacylglycerols. Only the HFHFr diet leads to a marked increase in the expression of enzymes involved in DNL and triglyceride metabolism, such as carbohydrate response element binding protein β (ChREBPβ, x3.2), a transcription factor that regulates DNL, and patatin-like phospholipase domain-containing 3 (PNPLA3, x2.6), a lipase that mobilizes stored triglycerides for VLDL secretion. Conclusion: The addition of liquid-fructose to dietary FA is determinant in liver steatosis and hypertriglyceridemia production, through increased DNL and PNPLA3 expression, and reduced FA catabolism.This research was funded Grant SAF2017-82369-R funded by MCIN/AEI/ 10.13039/501100011033 and by ERDF A way of making Europe, Generalitat de Catalunya (2017 SGR 38). A.M.V. is a predoctoral fellow, BECAL grant program BCAL04-327, from the Government of Paraguay. A.S.-V. is recipient of the Instituto de Salud Carlos III Miguel Servet fellowship (grant CP II 17/00029).Wiley202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/54334http://dx.doi.org/10.1002/mnfr.202101115reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésMol Nutr Food Res. 2022 Apr;66(7):e2101115info:eu-repo/grantAgreement/ES/2PE/SAF2017-82369-R© 2022 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.http://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/543342026-06-12T07:21:37Z
dc.title.none.fl_str_mv ChREBP-driven DNL and PNPLA3 expression induced by liquid fructose are essential in the production of fatty liver and hypertriglyceridemia in a high-fat diet-fed rat model
title ChREBP-driven DNL and PNPLA3 expression induced by liquid fructose are essential in the production of fatty liver and hypertriglyceridemia in a high-fat diet-fed rat model
spellingShingle ChREBP-driven DNL and PNPLA3 expression induced by liquid fructose are essential in the production of fatty liver and hypertriglyceridemia in a high-fat diet-fed rat model
Velázquez, Ana Magdalena
NAFLD
Ceramides
Diacylglycerols
Fatty acid β-oxidation
Lipidomics
Liver steatosis
title_short ChREBP-driven DNL and PNPLA3 expression induced by liquid fructose are essential in the production of fatty liver and hypertriglyceridemia in a high-fat diet-fed rat model
title_full ChREBP-driven DNL and PNPLA3 expression induced by liquid fructose are essential in the production of fatty liver and hypertriglyceridemia in a high-fat diet-fed rat model
title_fullStr ChREBP-driven DNL and PNPLA3 expression induced by liquid fructose are essential in the production of fatty liver and hypertriglyceridemia in a high-fat diet-fed rat model
title_full_unstemmed ChREBP-driven DNL and PNPLA3 expression induced by liquid fructose are essential in the production of fatty liver and hypertriglyceridemia in a high-fat diet-fed rat model
title_sort ChREBP-driven DNL and PNPLA3 expression induced by liquid fructose are essential in the production of fatty liver and hypertriglyceridemia in a high-fat diet-fed rat model
dc.creator.none.fl_str_mv Velázquez, Ana Magdalena
Bentanachs, Roger
Sala Vila, Aleix
Lázaro, Iolanda
Rodríguez-Morató, Jose, 1987-
Sánchez, Rosa María
Alegret i Jordà, Marta
Roglans i Ribas, Núria
Laguna, Juan Carlos
author Velázquez, Ana Magdalena
author_facet Velázquez, Ana Magdalena
Bentanachs, Roger
Sala Vila, Aleix
Lázaro, Iolanda
Rodríguez-Morató, Jose, 1987-
Sánchez, Rosa María
Alegret i Jordà, Marta
Roglans i Ribas, Núria
Laguna, Juan Carlos
author_role author
author2 Bentanachs, Roger
Sala Vila, Aleix
Lázaro, Iolanda
Rodríguez-Morató, Jose, 1987-
Sánchez, Rosa María
Alegret i Jordà, Marta
Roglans i Ribas, Núria
Laguna, Juan Carlos
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv NAFLD
Ceramides
Diacylglycerols
Fatty acid β-oxidation
Lipidomics
Liver steatosis
topic NAFLD
Ceramides
Diacylglycerols
Fatty acid β-oxidation
Lipidomics
Liver steatosis
description Scope: The aim of this study is to delineate the contribution of dietary saturated fatty acids (FA) versus liquid fructose to fatty liver and hypertriglyceridemia. Methods and results: Three groups of female rats are maintained for 3 months in standard chow (CT); High-fat diet (46.9% of fat-derived calories, rich in palmitic and stearic FA, HFD); and HFD with 10% w/v fructose in drinking water (HFHFr). Zoometric parameters, plasma biochemistry, and liver Oil-Red O (ORO) staining, lipidomics, and expression of proteins involved in FA metabolism are analyzed. Both diets increase ingested calories without modifying body weight. Only the HFHFr diet increases liver triglycerides (x11.0), with hypertriglyceridemia (x1.7) and reduces FA β-oxidation (x0.7), and increases liver FA markers of DNL (de novo lipogenesis). Whereas HFD livers show a high content of ceramides, HFHFr samples show unchanged ceramides, and an increase in diacylglycerols. Only the HFHFr diet leads to a marked increase in the expression of enzymes involved in DNL and triglyceride metabolism, such as carbohydrate response element binding protein β (ChREBPβ, x3.2), a transcription factor that regulates DNL, and patatin-like phospholipase domain-containing 3 (PNPLA3, x2.6), a lipase that mobilizes stored triglycerides for VLDL secretion. Conclusion: The addition of liquid-fructose to dietary FA is determinant in liver steatosis and hypertriglyceridemia production, through increased DNL and PNPLA3 expression, and reduced FA catabolism.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/54334
http://dx.doi.org/10.1002/mnfr.202101115
url http://hdl.handle.net/10230/54334
http://dx.doi.org/10.1002/mnfr.202101115
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Mol Nutr Food Res. 2022 Apr;66(7):e2101115
info:eu-repo/grantAgreement/ES/2PE/SAF2017-82369-R
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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