Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/121601
Title: | Hepatic regulation of VLDL receptor by PPARbeta/delta and FGF21 modulates non-alcoholic fatty liver disease |
Author: | Zarei, Mohammad Barroso Fernández, Emma Palomer Tarridas, Francesc Xavier Dai, Jianli Rada, Patricia Quesada López, Tania Paloma Escolà Gil, Joan Carles Cedó Giné, Lídia Zali, Mohammad Reza Molaei, Mahsa Dabiri, Reza Vázquez Cruz, Santiago Pujol Bech, Eugènia Valverde, Ángela M. Villarroya i Gombau, Francesc Liu, Yong Wahli, Walter Vázquez Carrera, Manuel |
Keywords: | Malalties del fetge Trastorns del metabolisme dels lípids Liver diseases Lipid metabolism disorders |
Issue Date: | 2018 |
Publisher: | Elsevier GmbH |
Abstract: | OBJECTIVE: 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)beta/delta and fibroblast growth factor 21 (FGF21) in hepatic VLDLR regulation. METHODS: Studies were conducted in wild-type and Pparbeta/delta-null mice, primary mouse hepatocytes, human Huh-7 hepatocytes, and liver biopsies from control subjects and patients with moderate and severe hepatic steatosis. RESULTS: Increased VLDLR levels were observed in liver of Pparbeta/delta-null mice and in Pparbeta/delta-knocked down mouse primary hepatocytes through mechanisms involving the heme-regulated eukaryotic translation initiation factor 2alpha (eIF2alpha) 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 PPARbeta/delta mRNA abundance and DNA-binding activity compared with control subjects. CONCLUSIONS: Overall, these findings provide new mechanisms by which PPARbeta/delta and FGF21 regulate VLDLR levels and influence hepatic steatosis development. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.molmet.2017.12.008 |
It is part of: | Molecular Metabolism, 2018, vol. 8, p. 117-131 |
URI: | http://hdl.handle.net/2445/121601 |
Related resource: | https://doi.org/10.1016/j.molmet.2017.12.008 |
ISSN: | 2212-8778 |
Appears in Collections: | Articles publicats en revistes (Institut de Biomedicina (IBUB)) Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
676367.pdf | 4.7 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License