dc.contributor.author |
Zarei, Mohammad |
dc.contributor.author |
Barroso, Emma |
dc.contributor.author |
Palomer, Xavier |
dc.contributor.author |
Dai, Jianli |
dc.contributor.author |
Rada, Patricia |
dc.contributor.author |
Quesada-López, Tania |
dc.contributor.author |
Escolà-Gil, Joan Carles |
dc.contributor.author |
Cedó, Lídia |
dc.contributor.author |
Zali, Mohammad Reza |
dc.contributor.author |
Molaei, Mahsa |
dc.contributor.author |
Dabiri, Reza |
dc.contributor.author |
Vázquez, Santiago |
dc.contributor.author |
Pujol Bech, Eugenia |
dc.contributor.author |
Valverde, Ángela M. |
dc.contributor.author |
Villarroya, Francesc |
dc.contributor.author |
Liu, Yong |
dc.contributor.author |
Wahli, Walter |
dc.contributor.author |
Vázquez-Carrera, Manuel |
dc.contributor.author |
Universitat Autònoma de Barcelona |
dc.date |
2018 |
dc.identifier |
https://ddd.uab.cat/record/190659 |
dc.identifier |
urn:10.1016/j.molmet.2017.12.008 |
dc.identifier |
urn:oai:ddd.uab.cat:190659 |
dc.identifier |
urn:pmid:29289645 |
dc.identifier |
urn:pmcid:PMC5985050 |
dc.identifier |
urn:pmc-uid:5985050 |
dc.identifier |
urn:articleid:22128778v8p117 |
dc.identifier |
urn:scopus_id:85041912233 |
dc.identifier |
urn:wos_id:000429084900011 |
dc.identifier |
urn:altmetric_id:30709859 |
dc.identifier |
urn:oai:egreta.uab.cat:publications/4458b6c0-c4c0-4c8c-8f9c-11655df31d47 |
dc.identifier |
urn:oai:pubmedcentral.nih.gov:5985050 |
dc.format |
application/pdf |
dc.language |
eng |
dc.publisher |
|
dc.relation |
Ministerio de Economía y Competitividad SAF2015-65267-R |
dc.relation |
Ministerio de Economía y Competitividad SAF2015-64146-R |
dc.relation |
Ministerio de Economía y Competitividad SAF2014-55725 |
dc.relation |
Molecular metabolism ; Vol. 8 (Feb. 2018), p. 117-131 |
dc.rights |
open access |
dc.rights |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. |
dc.rights |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
dc.subject |
VLDLR |
dc.subject |
PPAR |
dc.subject |
FGF21 |
dc.subject |
ATF4 |
dc.subject |
ER stress |
dc.subject |
ATF4, activating transcription factor 4 |
dc.subject |
Chop, C/EBP homologous protein |
dc.subject |
Eif2α, eukaryotic translation initiation factor 2α |
dc.subject |
FGF21, fibroblast growth factor 21 |
dc.subject |
HFD, high-fat diet |
dc.subject |
HRI, heme-regulated eIF2α kinase |
dc.subject |
NAFLD, non-alcoholic fatty liver disease |
dc.subject |
PPAR, peroxisome proliferator-activated receptor |
dc.title |
Hepatic regulation of VLDL receptor by PPARβ/δ and FGF21 modulates non-alcoholic fatty liver disease |
dc.type |
Article |
dc.description.abstract |
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. |