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PPAR-β/δ activation promotes phospholipid transfer protein expression
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2015
- Publisher :
- Elsevier, 2015.
-
Abstract
- 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.<br />This work was partly funded by European Cooperation in Science and Technology (COST) action BM0904, Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, FIS 11-0176 (to F.B.-V.) and FIS 12-00291 (to J.C.E.-G.), Academy of Finland (Grant #257545 to M.J.), and Ministerio de Economía y Competitividad, SAF2012-30708 (to M.V.-C.). CIBER de Diabetes y Enfermedades Metabólicas Asociadas is an Instituto de Salud Carlos III Project.
- Subjects :
- medicine.medical_specialty
HDL
Peroxisome proliferator-activated receptor
ABCA1
Biology
GW0742
Biochemistry
Phospholipid transfer protein
Cell Line
Mice
Downregulation and upregulation
Internal medicine
Gene expression
PPAR-β/δ
medicine
Animals
Humans
PPAR delta
Phospholipid Transfer Proteins
Receptor
PPAR-beta
Pharmacology
chemistry.chemical_classification
ApoA-I
Mice, Inbred C57BL
Thiazoles
Endocrinology
chemistry
LDL receptor
biology.protein
lipids (amino acids, peptides, and proteins)
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Accession number :
- edsair.doi.dedup.....4613b504e3c9f6577f1814d201c9ae91