Hepatic regulation of VLDL receptor by PPARβ/δ and FGF21 modulates non-alcoholic fatty liver disease.

Détails

Ressource 1Télécharger: 1-s2.0-S2212877817306622-main.pdf (4593.65 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_4C931839E09D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Hepatic regulation of VLDL receptor by PPARβ/δ and FGF21 modulates non-alcoholic fatty liver disease.
Périodique
Molecular metabolism
Auteur(s)
Zarei M., Barroso E., Palomer X., Dai J., Rada P., Quesada-López T., Escolà-Gil J.C., Cedó L., Zali M.R., Molaei M., Dabiri R., Vázquez S., Pujol E., Valverde Á.M., Villarroya F., Liu Y., Wahli W., Vázquez-Carrera M.
ISSN
2212-8778 (Electronic)
ISSN-L
2212-8778
Statut éditorial
Publié
Date de publication
02/2018
Peer-reviewed
Oui
Volume
8
Pages
117-131
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The very low-density lipoprotein receptor (VLDLR) plays an important role in the development of hepatic steatosis. In this study, we investigated the role of Peroxisome Proliferator-Activated Receptor (PPAR)β/δ and fibroblast growth factor 21 (FGF21) in hepatic VLDLR regulation.
Studies were conducted in wild-type and Pparβ/δ-null mice, primary mouse hepatocytes, human Huh-7 hepatocytes, and liver biopsies from control subjects and patients with moderate and severe hepatic steatosis.
Increased VLDLR levels were observed in liver of Pparβ/δ-null mice and in Pparβ/δ-knocked down mouse primary hepatocytes through mechanisms involving the heme-regulated eukaryotic translation initiation factor 2α (eIF2α) kinase (HRI), activating transcription factor (ATF) 4 and the oxidative stress-induced nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathways. Moreover, by using a neutralizing antibody against FGF21, Fgf21-null mice and by treating mice with recombinant FGF21, we show that FGF21 may protect against hepatic steatosis by attenuating endoplasmic reticulum (ER) stress-induced VLDLR upregulation. Finally, in liver biopsies from patients with moderate and severe hepatic steatosis, we observed an increase in VLDLR levels that was accompanied by a reduction in PPARβ/δ mRNA abundance and DNA-binding activity compared with control subjects.
Overall, these findings provide new mechanisms by which PPARβ/δ and FGF21 regulate VLDLR levels and influence hepatic steatosis development.
Mots-clé
Activating Transcription Factor 4/genetics, Activating Transcription Factor 4/metabolism, Animals, Cell Line, Tumor, Female, Fibroblast Growth Factors/genetics, Fibroblast Growth Factors/metabolism, Humans, Liver/metabolism, Male, Mice, Mice, Inbred C57BL, Non-alcoholic Fatty Liver Disease/metabolism, PPAR delta/genetics, PPAR delta/metabolism, PPAR-beta/genetics, PPAR-beta/metabolism, Receptors, LDL/genetics, Receptors, LDL/metabolism, Signal Transduction, eIF-2 Kinase/genetics, eIF-2 Kinase/metabolism, ATF4, ER stress, FGF21, PPAR, VLDLR
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2018 19:31
Dernière modification de la notice
20/08/2019 15:01
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