Back
Pharmacological PPARβ/δ activation upregulates VLDLR in hepatocytes.
Journal article

Pharmacological PPARβ/δ activation upregulates VLDLR in hepatocytes.

  • Zarei M Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain; Spanish Biomedical Research Center in Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Spain; Research Institute, Hospital Sant Joan de Déu, Barcelona, Spain.
  • Barroso E Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain; Spanish Biomedical Research Center in Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Spain; Research Institute, Hospital Sant Joan de Déu, Barcelona, Spain.
  • Palomer X Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain; Spanish Biomedical Research Center in Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Spain; Research Institute, Hospital Sant Joan de Déu, Barcelona, Spain.
  • Escolà-Gil JC Spanish Biomedical Research Center in Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Spain; Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain; Departament de Bioquímica i Biología Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • Cedó L Spanish Biomedical Research Center in Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Spain; Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain; Departament de Bioquímica i Biología Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • Wahli W Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore; INRA ToxAlim, UMR1331, Chemin de Tournefeuille, Toulouse Cedex, France.
  • Vázquez-Carrera M Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain; Spanish Biomedical Research Center in Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Spain; Research Institute, Hospital Sant Joan de Déu, Barcelona, Spain. Electronic address: mvazquezcarrera@ub.edu.
Show more…
  • 2019-04-17
Published in:
  • Clinica e investigacion en arteriosclerosis : publicacion oficial de la Sociedad Espanola de Arteriosclerosis. - 2019
EHGNA
NAFLD
PPAR
VLDLR
Animals
Cells, Cultured
Disease Models, Animal
Hepatocytes
Humans
Hypolipidemic Agents
Liver
Male
Mice
Mice, Knockout
Non-alcoholic Fatty Liver Disease
PPAR delta
PPAR-beta
Receptors, LDL
Thiazoles
Triglycerides
Up-Regulation
English The very low-density lipoprotein receptor (VLDLR) plays an important function in the control of serum triglycerides and in the development of non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the role of peroxisome proliferator-activated receptor (PPAR)β/δ activation in hepatic VLDLR regulation. Treatment of mice fed a high-fat diet with the PPARβ/δ agonist GW501516 increased the hepatic expression of Vldlr. Similarly, exposure of human Huh-7 hepatocytes to GW501516 increased the expression of VLDLR and triglyceride accumulation, the latter being prevented by VLDLR knockdown. Finally, treatment with another PPARβ/δ agonist increased VLDLR levels in the liver of wild-type mice, but not PPARβ/δ-deficient mice, confirming the regulation of hepatic VLDLR by this nuclear receptor. Our results suggest that upregulation of hepatic VLDLR by PPARβ/δ agonists might contribute to the hypolipidemic effect of these drugs by increasing lipoprotein delivery to the liver. Overall, these findings provide new effects by which PPARβ/δ regulate VLDLR levels and may influence serum triglyceride levels and NAFLD development.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/248878
Statistics
Document views: 26 File downloads: