Bile secretory function in the obese Zucker rat: evidence of cholestasis and altered canalicular transport function

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dc.contributor.authorPizarro, M
dc.contributor.authorBalasubramaniyan, N
dc.contributor.authorSolis, N
dc.contributor.authorSolar, A
dc.contributor.authorDuarte, I
dc.contributor.authorMiquel, JF
dc.contributor.authorSuchy, FJ
dc.contributor.authorTrauner, M
dc.contributor.authorAccatino, L
dc.contributor.authorAnanthanarayanan, M
dc.contributor.authorArrese, M
dc.date.accessioned2024-01-10T12:37:48Z
dc.date.available2024-01-10T12:37:48Z
dc.date.issued2004
dc.description.abstractBackground: Obese Zucker rats (ZR) have been used as an experimental model for non-alcoholic fatty liver disease and are particularly susceptible to various types of liver injury. Bile secretory function has not been assessed in ZR.
dc.description.abstractAim: To study bile secretion and expression of the main hepatobiliary transporters in ZR.
dc.description.abstractMethods: Bile flow and biliary secretion of lipids and glutathione were determined in eight and 14 week old obese ZR and their lean controls. Protein mass and mRNA of the Na+/taurocholate cotransporting polypeptide ( Ntcp), the bile salt export pump (Bsep), and the multidrug resistant associated protein 2 (Mrp2) were assessed by western and northern blot, respectively. The effects of administration of a tumour necrosis factor alpha inactivator ( etanercept) and an insulin sensitiser ( rosiglitazone) were assessed in obese ZR while leptin was given to non-obese rats to study its effect on Mrp2 expression.
dc.description.abstractResults: ZR exhibited increased body weight and hyperlipidaemia. Only 14 week old obese ZR has fatty liver. Decreased bile flow and biliary lipid and glutathione secretion as well as reduced hepatic transport of both taurocholate and bromosulphthalein were found in obese ZR. Hepatic Mrp2 protein mass was markedly reduced (-70%) in obese rats while Ntcp and Bsep protein levels were similar to lean rats. Downregulation of Mrp2 seems to involve both transcriptional and post-transcriptional mechanisms probably related to insulin and leptin resistance.
dc.description.abstractConclusions: Obese ZR exhibit an impaired bile secretory function with significant functional and molecular alterations consistent with mild cholestasis. A defective hepatobiliary transport capacity may be a contributory factor in rendering the obese ZR more susceptible to liver injury.
dc.description.funderNICHD NIH HHS
dc.description.funderEUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT
dc.fechaingreso.objetodigital2024-05-02
dc.format.extent7 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1136/gut.2003.037689
dc.identifier.eissn1468-3288
dc.identifier.issn0017-5749
dc.identifier.pubmedidMEDLINE:15542525
dc.identifier.urihttps://doi.org/10.1136/gut.2003.037689
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/76927
dc.identifier.wosidWOS:000225059900025
dc.information.autorucMedicina;Accatino L;S/I;99016
dc.information.autorucMedicina;Arrese M;S/I;76095
dc.information.autorucMedicina;Miquel J;S/I;72216
dc.issue.numero12
dc.language.isoen
dc.nota.accesoSin adjunto
dc.pagina.final1843
dc.pagina.inicio1837
dc.publisherBMJ PUBLISHING GROUP
dc.revistaGUT
dc.rightsregistro bibliográfico
dc.subjectORGANIC ANION TRANSPORTERS
dc.subjectSALT EXPORT PUMP
dc.subjectBILIARY GLUTATHIONE
dc.subjectHEPATIC STEATOSIS
dc.subjectLIVER-INJURY
dc.subjectEXPRESSION
dc.subjectACID
dc.subjectRESISTANCE
dc.subjectMULTIDRUG
dc.subjectSTEATOHEPATITIS
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleBile secretory function in the obese Zucker rat: evidence of cholestasis and altered canalicular transport function
dc.typeartículo
dc.volumen53
sipa.codpersvinculados99016
sipa.codpersvinculados76095
sipa.codpersvinculados72216
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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