Fibrates down-regulate hepatic scavenger receptor class B type I protein expression in mice

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dc.contributor.authorMardones, P
dc.contributor.authorPilon, A
dc.contributor.authorBouly, M
dc.contributor.authorDuran, D
dc.contributor.authorNishimoto, T
dc.contributor.authorArai, H
dc.contributor.authorKozarsky, KF
dc.contributor.authorAltayo, M
dc.contributor.authorMiquel, JF
dc.contributor.authorLuc, G
dc.contributor.authorClavey, V
dc.contributor.authorStaels, B
dc.contributor.authorRigotti, A
dc.date.accessioned2024-01-10T13:13:06Z
dc.date.available2024-01-10T13:13:06Z
dc.date.issued2003
dc.description.abstractFibrates are normolipidemic drugs used in atherogenic dyslipidemia because of their ability to raise high density lipoprotein (HDL) and decrease triglyceride levels. They exert multiple effects on lipid metabolism by activating the peroxisome proliferator-activated receptor-a (PPAR-alpha), which controls the transcriptional regulation of genes involved in hepatic fatty acid, cholesterol, and lipoprotein metabolism. The hepatic expression of the scavenger receptor class B type I (SR-BI) plays a critical role in lipoprotein metabolism, mainly due to its ability to mediate selective cholesterol uptake. Because fibrates and PPAR-alpha agonists upregulate SR-BI expression in human and murine macrophages, we tested whether fibrates raised a similar regulatory response on hepatic SR-BI expression in mice. Surprisingly, fibrate treatment suppressed SR-BI protein expression in the liver without changing steady state SR-BI mRNA levels. Decreased hepatic SR-BI protein expression correlated with enlarged HDL particle size. This effect was concomitant with down-regulation of CLAMP, a putative SR-BI-stabilizing protein found in the hepatic plasma membrane, which was also not associated to changes in CLAMP mRNA levels. The posttranscriptional regulatory effect of fibrates over hepatic SR-BI protein levels was dependent on PPAR-alpha expression, because it was absent in PPAR-alpha-deficient mice. Restoring hepatic SR-BI expression in fibrate-treated mice by recombinant adenoviral gene transfer abolished fibrate-mediated HDL particle size enlargement. This study describes a novel effect of fibrates on hepatic SR-BI expression providing an alternative mechanism by which this drug family modulates HDL metabolism in vivo.
dc.fechaingreso.objetodigital2024-04-25
dc.format.extent7 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1074/jbc.M211627200
dc.identifier.eissn1083-351X
dc.identifier.issn0021-9258
dc.identifier.pubmedidMEDLINE:12511553
dc.identifier.urihttps://doi.org/10.1074/jbc.M211627200
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/78266
dc.identifier.wosidWOS:000181466800019
dc.information.autorucMedicina;Miquel J;S/I;72216
dc.information.autorucMedicina;Rigotti A;S/I;68489
dc.issue.numero10
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final7890
dc.pagina.inicio7884
dc.publisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
dc.revistaJOURNAL OF BIOLOGICAL CHEMISTRY
dc.rightsacceso abierto
dc.subjectHIGH-DENSITY-LIPOPROTEIN
dc.subjectPROLIFERATOR-ACTIVATED RECEPTORS
dc.subjectCORONARY-ARTERY-DISEASE
dc.subjectAPOLIPOPROTEIN-A-I
dc.subjectSR-BI
dc.subjectDEFICIENT MICE
dc.subjectPPAR-ALPHA
dc.subjectRAT-LIVER
dc.subjectCHOLESTEROL
dc.subjectHDL
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleFibrates down-regulate hepatic scavenger receptor class B type I protein expression in mice
dc.typeartículo
dc.volumen278
sipa.codpersvinculados72216
sipa.codpersvinculados68489
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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