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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 |
Author: | Velázquez, Ana Magdalena Bentanachs Raset, Roger Sala Vila, Aleix Lázaro, Iolanda Rodríguez-Morató, J. Sánchez Peñarroya, Rosa M Alegret i Jordà, Marta Roglans i Ribas, Núria Laguna Egea, Juan Carlos |
Keywords: | Fetge Malalties del fetge Metabolisme dels lípids Liver Liver diseases Lipid metabolism |
Issue Date: | 6-Feb-2022 |
Publisher: | Wiley-VCH |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1002/mnfr.202101115 |
It is part of: | Molecular Nutrition & Food Research, 2022 |
URI: | http://hdl.handle.net/2445/183948 |
Related resource: | https://doi.org/10.1002/mnfr.202101115 |
ISSN: | 1613-4125 |
Appears in Collections: | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) |
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