Please use this identifier to cite or link to this item:
|Title:||Hepatic regulation of VLDL receptor by PPARβ/δ and FGF21 modulates non-alcoholic fatty liver disease||Authors:||Mohammad Zarei
Escolà-Gil, Joan Carles
Mohammad Reza Zali
Valverde, Ángela M.
|Issue Date:||2017||Source:||Mohammad Zarei, Barroso, E., Palomer, X., Dai, J., Rada, P., Quesada-López, T., et al. (2018). Hepatic regulation of VLDL receptor by PPARβ/δ and FGF21 modulates non-alcoholic fatty liver disease. Molecular Metabolism, 8, 117-131.||Series/Report no.:||Molecular Metabolism||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)β/δ and fibroblast growth factor 21 (FGF21) in hepatic VLDLR regulation. Methods: 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. Results: 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. Conclusions: Overall, these findings provide new mechanisms by which PPARβ/δ and FGF21 regulate VLDLR levels and influence hepatic steatosis development.||URI:||https://hdl.handle.net/10356/85541
|ISSN:||2212-8778||DOI:||10.1016/j.molmet.2017.12.008||Rights:||© 2017 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||LKCMedicine Journal Articles|
Files in This Item:
|Hepatic regulation of VLDL receptor by PPARβ or δ and FGF21 modulates non-alcoholic fatty liver disease.pdf||4.7 MB||Adobe PDF|
Updated on Mar 3, 2021
Updated on Mar 9, 2021
Page view(s) 50409
Updated on Jul 5, 2022
Updated on Jul 5, 2022
Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.