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Título: | PPAR-β/δ activation promotes phospholipid transfer protein expression |
Autor: | Chehaibi, Khouloud; Cedó, Lídia; Santos, David; Blanco-Vaca, Francisco; Escolà-Gil, Joan Carles | Palabras clave: | PPAR-β/δ Phospholipid transfer protein Mice ApoA-I ABCA1 HDL |
Fecha de publicación: | 15-mar-2015 | Editor: | Elsevier | Citación: | Biochemical Pharmacology 94(2): 101-108 (2015) | Resumen: | The peroxisome proliferator-activated receptor (PPAR)-β/δ has emerged as a promising therapeutic target for treating dyslipidemia, including beneficial effects on HDL cholesterol (HDL-C). In the current study, we determined the effects of the PPAR-β/δ agonist GW0742 on HDL composition and the expression of liver HDL-related genes in mice and cultured human cells. The experiments were carried out in C57BL/6 wild-type, LDL receptor (LDLR)-deficient mice and PPAR-β/δ-deficient mice treated with GW0742 (10 mg/kg/day) or a vehicle solution for 14 days. GW0742 upregulated liver phospholipid transfer protein (Pltp) gene expression and increased serum PLTP activity in mice. When given to wild-type mice, GW0742 significantly increased serum HDL-C and HDL phospholipids; GW0742 also raised serum potential to generate preβ-HDL formation. The GW0742-mediated effects on liver Pltp expression and serum enzyme activity were completely abolished in PPAR-β/δ-deficient mice. GW0742 also stimulated PLTP mRNA expression in mouse J774 macrophages, differentiated human THP-1 macrophages and human hepatoma Huh7. Collectively, our findings demonstrate a common transcriptional upregulation by GW0742-activated PPAR-β/δ of Pltp expression in cultured cells and in mouse liver resulting in enhanced serum PLTP activity. Our results also indicate that PPAR-β/δ activation may modulate PLTP-mediated preβ-HDL formation and macrophage cholesterol efflux. © 2015 Elsevier Inc. | Versión del editor: | https://doi.org/10.1016/j.bcp.2015.01.016 | URI: | http://hdl.handle.net/10261/148509 | DOI: | 10.1016/j.bcp.2015.01.016 | Identificadores: | doi: 10.1016/j.bcp.2015.01.016 issn: 1873-2968 |
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