PPAR-β/δ activation promotes phospholipid transfer protein expression

被引：27

作者：

Chehaibi, Khouloud ^{[1
,2
]}

Cedo, Lidia ^{[1
,3
]}

Metso, Jari ^{[4
]}

Palomer, Xavier ^{[3
,5
]}

Santos, David ^{[1
,3
]}

Quesada, Helena ^{[1
,3
]}

Slimane, Mohamed Naceur ^{[2
]}

Wahli, Walter ^{[6
,7
]}

Julve, Josep ^{[1
,3
,8
]}

Vazquez-Carrera, Manuel ^{[3
,5
]}

Jauhiainen, Matti ^{[4
]}

Blanco-Vaca, Francisco ^{[1
,3
,8
]}

Carles Escola-Gil, Joan ^{[1
,3
,8
]}

机构：

[1] IIB, Barcelona, Spain

[2] Univ Monastir, Fac Med, Monastir, Tunisia

[3] CIBERDEM, Barcelona, Spain

[4] Natl Inst Hlth & Welf, Biomedicum, Publ Hlth Genom & Biomarkers Unit, Helsinki, Finland

[5] Univ Barcelona, Fac Pharm, Barcelona, Spain

[6] Univ Lausanne, Quartier UNIL Sorge, Natl Res Ctr Frontiers Genet, Integrat Gen, CH-1015 Lausanne, Switzerland

[7] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 169856, Singapore

[8] Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, E-08193 Barcelona, Spain

来源：

BIOCHEMICAL PHARMACOLOGY | 2015年 / 94卷 / 02期

基金：

芬兰科学院;

关键词：

apoA-I; ABCA1; HDL; Mice; Phospholipid transfer protein; PPAR-beta/delta; HIGH-DENSITY-LIPOPROTEIN; RECEPTOR-DELTA AGONIST; REVERSE CHOLESTEROL; GENE-EXPRESSION; TRANSPORTER A1; ATHEROSCLEROSIS; INCREASES; PLTP; MICE; DEFICIENCY;

D O I：

10.1016/j.bcp.2015.01.016

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The peroxisome proliferator-activated receptor (PPAR)-beta/delta 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-beta/delta 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-beta/delta-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 wildtype mice, GW0742 significantly increased serum HDL-C and HDL phospholipids; GW0742 also raised serum potential to generate prep-HDL formation. The GW0742-mediated effects on liver Pltp expression and serum enzyme activity were completely abolished in PPAR-beta/delta-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-beta/delta of Pltp expression in cultured cells and in mouse liver resulting in enhanced serum PLTP activity. Our results also indicate that PPAR-beta/delta activation may modulate PLTP-mediated prep-HDL formation and macrophage cholesterol efflux. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：101 / 108

页数：8

共 40 条

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