PPAR-β/δ activation promotes phospholipid transfer protein expression

Khouloud Chehaibi, Lídia Cedó, Jari Metso, Xavier Palomer, David Santos, Helena Quesada, Mohamed Naceur Slimane, Walter Wahli, Josep Julve, Manuel Vázquez-Carrera, Matti Jauhiainen, Francisco Blanco-Vaca, Joan Carles Escolà-Gil

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)

Abstract

© 2015 Elsevier Inc. 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.
Original languageEnglish
Pages (from-to)101-108
JournalBiochemical Pharmacology
Volume94
Issue number2
DOIs
Publication statusPublished - 15 Mar 2015

Keywords

  • ABCA1
  • apoA-I
  • HDL
  • Mice
  • Phospholipid transfer protein
  • PPAR-β/δ

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