visitant ::
identificació
|
|||||||||||||||
Cerca | Lliura | Ajuda | Servei de Biblioteques | Sobre el DDD | Català English Español |
Pàgina inicial > Articles > Articles publicats > Hepatic regulation of VLDL receptor by PPARβ/δ and FGF21 modulates non-alcoholic fatty liver disease |
Data: | 2018 |
Resum: | 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. |
Ajuts: | Ministerio de Economía y Competitividad SAF2015-65267-R Ministerio de Economía y Competitividad SAF2015-64146-R Ministerio de Economía y Competitividad SAF2014-55725 |
Drets: | 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. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Matèria: | VLDLR ; PPAR ; FGF21 ; ATF4 ; ER stress ; ATF4, activating transcription factor 4 ; Chop, C/EBP homologous protein ; Eif2α, eukaryotic translation initiation factor 2α ; FGF21, fibroblast growth factor 21 ; HFD, high-fat diet ; HRI, heme-regulated eIF2α kinase ; NAFLD, non-alcoholic fatty liver disease ; PPAR, peroxisome proliferator-activated receptor |
Publicat a: | Molecular metabolism, Vol. 8 (Feb. 2018) , p. 117-131, ISSN 2212-8778 |
15 p, 4.6 MB |