title: PPAR-β/δ activation promotes phospholipid transfer protein expression.
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 (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 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.
authors: Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain; Faculty of Medicine, University of Monastir, Monastir, Tunisia.
authors: Khouloud
authors: K
authors: Chehaibi
authors: Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors: Lídia
authors: L
authors: Cedó
authors: National Institute for Health and Welfare, Public Health Genomics and Biomarkers Unit, Biomedicum, Helsinki, Finland.
authors: Jari
authors: J
authors: Metso
authors: CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors: Xavier
authors: X
authors: Palomer
authors: Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors: David
authors: D
authors: Santos
authors: Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors: Helena
authors: H
authors: Quesada
authors: Faculty of Medicine, University of Monastir, Monastir, Tunisia.
authors: Mohamed
authors: M
authors: Naceur Slimane
authors: Center for Integrative Genomics, National Research Center Frontiers in Genetics, University of Lausanne, Quartier UNIL-Sorge, Bâtiment Génopode, CH-1015 Lausanne, Switzerland; Lee Kong Chian School of Medicine, Nanyang Technological University, The Academia, 20 College Road, Singapore 169856 Singapore.
authors: Walter
authors: W
authors: Wahli
authors: Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Departament de Bioquímica i Biología Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: Josep
authors: J
authors: Julve
authors: CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors: Manuel
authors: M
authors: Vázquez-Carrera
authors: National Institute for Health and Welfare, Public Health Genomics and Biomarkers Unit, Biomedicum, Helsinki, Finland.
authors: Matti
authors: M
authors: Jauhiainen
authors: Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Departament de Bioquímica i Biología Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: fblancova@santpau.cat.
authors: Francisco
authors: F
authors: Blanco-Vaca
authors: Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Departament de Bioquímica i Biología Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: jescola@santpau.cat.
authors: Joan Carles
authors: JC
authors: Escolà-Gil
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D047494:PPAR delta / Q000819:agonists / Q000378:metabolism*; D048068:PPAR-beta / Q000819:agonists / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D010636:Phenols; D013438:Sulfhydryl Compounds
chemical_list: D047494:PPAR delta; D048068:PPAR-beta; D049294:Phospholipid Transfer Proteins; D013844:Thiazoles; C479979:(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid; D010636:Phenols; D013438:Sulfhydryl Compounds
keywords: ABCA1; HDL; Mice; PPAR-β/δ; Phospholipid transfer protein; apoA-I