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

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  • dc.contributor.author Velázquez, Ana Magdalena
  • dc.contributor.author Bentanachs, Roger
  • dc.contributor.author Sala Vila, Aleix
  • dc.contributor.author Lázaro, Iolanda
  • dc.contributor.author Rodríguez-Morató, Jose, 1987-
  • dc.contributor.author Sánchez, Rosa María
  • dc.contributor.author Alegret i Jordà, Marta
  • dc.contributor.author Roglans i Ribas, Núria
  • dc.contributor.author Laguna, Juan Carlos
  • dc.date.accessioned 2022-10-11T06:11:49Z
  • dc.date.available 2022-10-11T06:11:49Z
  • dc.date.issued 2022
  • dc.description.abstract 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.
  • dc.description.sponsorship 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).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Velázquez AM, Bentanachs R, Sala-Vila A, Lázaro I, Rodríguez-Morató J, Sánchez RM, Alegret M, Roglans N, Laguna JC. 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. Mol Nutr Food Res. 2022 Apr;66(7):e2101115. DOI: 10.1002/mnfr.202101115
  • dc.identifier.doi http://dx.doi.org/10.1002/mnfr.202101115
  • dc.identifier.issn 1613-4125
  • dc.identifier.uri http://hdl.handle.net/10230/54334
  • dc.language.iso eng
  • dc.publisher Wiley
  • dc.relation.ispartof Mol Nutr Food Res. 2022 Apr;66(7):e2101115
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-82369-R
  • dc.rights © 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.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
  • dc.subject.keyword NAFLD
  • dc.subject.keyword Ceramides
  • dc.subject.keyword Diacylglycerols
  • dc.subject.keyword Fatty acid β-oxidation
  • dc.subject.keyword Lipidomics
  • dc.subject.keyword Liver steatosis
  • dc.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
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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