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Bulk Droplet Vitrification for Primary Hepatocyte Preservation
Published on: October 25, 2019
Pharmacological PPARβ/δ activation upregulates VLDLR in hepatocytes
Mohammad Zarei1, Emma Barroso1, Xavier Palomer1
1Department 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.
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.
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