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Title: Pharmacological PPARβ/δ activation upregulates VLDLR in hepatocytes
Authors: Zarei, Mohammad
Barroso, Emma
Palomer, Xavier
Escolà-Gil, Joan Carles
Cedó, Lidia
Wahli, Walter
Vázquez-Carrera, Manuel
Keywords: Science::Medicine
Issue Date: 2019
Source: Zarei, M., Barroso, E., Palomer, X., Escolà-Gil, J. C., Cedó, L., Wahli, W., & Vázquez-Carrera, M. (2019). Pharmacological PPARβ/δ activation upregulates VLDLR in hepatocytes. Clínica e Investigación en Arteriosclerosis, 31(3), 111-118. doi:10.1016/j.arteri.2019.01.004
Journal: Clínica e Investigación en Arteriosclerosis
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.
ISSN: 0214-9168
DOI: 10.1016/j.arteri.2019.01.004
Rights: © 2019 Sociedad Española de Arteriosclerosis. Published by Elsevier España, S.L.U. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
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