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Quercetin ameliorates dysregulation of lipid metabolism genes via the PI3K/AKT pathway in a diet‐induced mouse model of nonalcoholic fatty liver disease
Author(s) -
PisoneroVaquero Sandra,
MartínezFerreras Ángel,
GarcíaMediavilla María Victoria,
MartínezFlórez Susana,
Fernández Anna,
Benet Marta,
Olcoz José Luis,
Jover Ramiro,
GonzálezGallego Javier,
SánchezCampos Sonia
Publication year - 2015
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.201400913
Subject(s) - pi3k/akt/mtor pathway , nonalcoholic fatty liver disease , protein kinase b , lipid metabolism , biology , fatty liver , signal transduction , chemistry , microbiology and biotechnology , biochemistry , medicine , disease
Scope Flavonoids and related compounds seem to have favorable effects on nonalcoholic fatty liver disease (NAFLD) progression, although the exact mechanisms implicated are poorly understood. In this study, we aimed to investigate the effect of the flanovol quercetin on gene expression deregulation involved in the development of NAFLD, as well as the possible implication of phosphatidylinositol 3‐kinase (PI3K)/AKT pathway modulation. Methods and results We used an in vivo model based on methionine‐ and choline‐deficient (MCD) diet‐fed mice and an in vitro model consisting of Huh7 cells incubated with MCD medium. MCD‐fed mice showed classical pathophysiological characteristics of nonalcoholic steatohepatitis, associated with altered transcriptional regulation of fatty acid uptake‐ and trafficking‐related gene expression, with increased lipoperoxidation. PI3K/AKT pathway was activated by MCD and triggered gene deregulation causing either activation or inhibition of all studied genes as demonstrated through cell incubation with the PI3K‐inhibitor LY294002. Treatment with quercetin reduced AKT phosphorylation, and oxidative/nitrosative stress, inflammation and lipid metabolism‐related genes displayed a tendency to normalize in both in vivo and in vitro models. Conclusion These results place quercetin as a potential therapeutic strategy for preventing NAFLD progression by attenuating gene expression deregulation, at least in part through PI3K/AKT pathway inactivation.