| First Author | Chehaibi K | Year | 2015 |
| Journal | Biochem Pharmacol | Volume | 94 |
| Issue | 2 | Pages | 101-8 |
| PubMed ID | 25662586 | Mgi Jnum | J:219883 |
| Mgi Id | MGI:5629902 | Doi | 10.1016/j.bcp.2015.01.016 |
| Citation | Chehaibi K, et al. (2015) PPAR-beta/delta activation promotes phospholipid transfer protein expression. Biochem Pharmacol 94(2):101-8 |
| abstractText | 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 (10mg/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 prebeta-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 prebeta-HDL formation and macrophage cholesterol efflux. |
