کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2512079 | 1118312 | 2015 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: PPAR-β/δ activation promotes phospholipid transfer protein expression PPAR-β/δ activation promotes phospholipid transfer protein expression](/preview/png/2512079.png)
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.
PPAR-β/δ activation increases pltp expression in liver and macrophages. Serum PLTP may promote macrophage cholesterol efflux by inducing the generation of preβ-HDL. Furthermore, macrophage PLTP may promote ABCA1-mediated cholesterol efflux.Figure optionsDownload as PowerPoint slide
Journal: Biochemical Pharmacology - Volume 94, Issue 2, 15 March 2015, Pages 101–108