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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(s) -
Velázquez Ana Magdalena,
Bentanachs Roger,
SalaVila Aleix,
Lázaro Iolanda,
RodríguezMorató Jose,
Sánchez Rosa M.,
Alegret Marta,
Roglans Núria,
Laguna Juan Carlos
Publication year - 2022
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.202101115
Subject(s) - endocrinology , medicine , hypertriglyceridemia , lipogenesis , carbohydrate responsive element binding protein , fatty liver , steatosis , triglyceride , chemistry , lipoprotein lipase , lipid metabolism , fructose , biology , biochemistry , adipose tissue , cholesterol , transcription factor , disease , gene
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.