Velázquez, Ana MagdalenaBentanachs, RogerSala Vila, AleixLázaro, IolandaRodríguez-Morató, Jose, 1987-Sánchez, Rosa MaríaAlegret i Jordà, MartaRoglans i Ribas, NúriaLaguna, Juan Carlos2022-10-112022-10-112022Velázquez 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.2021011151613-4125http://hdl.handle.net/10230/54334Scope: 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.application/pdfeng© 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.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1002/mnfr.202101115NAFLDCeramidesDiacylglycerolsFatty acid β-oxidationLipidomicsLiver steatosisinfo:eu-repo/semantics/openAccess