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Clin Investig Arterioscler. 2019 May - Jun;31(3):111-118. doi: 10.1016/j.arteri.2019.01.004. Epub 2019 Apr 13.

Pharmacological PPARβ/δ activation upregulates VLDLR in hepatocytes.

[Article in English, Spanish]

Author information

1
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.
2
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.
3
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.
4
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.

Abstract

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.

KEYWORDS:

EHGNA; NAFLD; PPAR; VLDLR

PMID:
30987865
DOI:
10.1016/j.arteri.2019.01.004
[Indexed for MEDLINE]

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