Increased activity of hepatic microsomal triglyceride transfer protein and bile acid synthesis in gallstone disease

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dc.contributor.authorCastro, Juan
dc.contributor.authorAmigo, Ludwig
dc.contributor.authorMiquel, Juan Francisco
dc.contributor.authorGalman, Cecilia
dc.contributor.authorCrovari, Fernando
dc.contributor.authorRaddatz, Alejandro
dc.contributor.authorZanlungo, Silvana
dc.contributor.authorJalil, Roberto
dc.contributor.authorRudling, Mats
dc.contributor.authorNervi, Flavio
dc.date.accessioned2024-01-10T13:49:22Z
dc.date.available2024-01-10T13:49:22Z
dc.date.issued2007
dc.description.abstractA strong interrelationship exists between the regulation of bile acid (BA) metabolism and hepatic very low density lipoprotein (VLDL) production. We have recently shown that BA synthesis is increased in gallstone disease. We investigated the activity of hepatic microsomal triglyceride transfer protein (MTTP) as a surrogate of VLDL production, BA synthesis, and mRNA expression levels of proteins that regulate fatty acid (FA) metabolism in the liver of gallstone (GS) patients compared with GS-free patients. Twenty-seven volunteers subjected to elective surgery; 9 were GS-free and 18 with GS agreed to have a liver biopsy. We quantified by a fluorescence assay the activity of MTTP and by quantitative reverse-transcription PCR (RT-PCR) the mRNA content of hepatic MTTP and genes that regulate hepatic sterol and FA metabolism. Plasma was assayed for lathosterol and 7 alpha-hydroxy-4-cholesten-3-one. Liver histology was normal in GS and GS-free patients. Serum VLDL triglycerides and apoB were significantly increased in GS. Hepatic triglycerides tripled in GS (P < 0.001) compared with GS-free. MTTP activity increased 70% (P < 0.001). Serum lathosterol and hepatic cholesterol concentrations, and mRNA expressions of MTTP, CD36, and FABP1 were similar in GS-free and GS patients. Hepatic mRNA expression of hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) and 3-hydroxyl-3-methyl-glutaryl-CoA synthase (HMGS) were significantly decreased- 40% and 27%, respectively in GS. Serum 7a-hydroxy-4-cholesten-3-one was 75% higher, and mRNA expression of CYP7A1 was increased sevenfold (P < 0.001) in GS. Conclusion: Hepatic MTTP activity and BA synthesis are increased in GS. Results suggest that hepatic VLDL production and trafficking of BA are increased in gallstone patients.
dc.fechaingreso.objetodigital05-04-2024
dc.format.extent6 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1002/hep.21616
dc.identifier.issn0270-9139
dc.identifier.pubmedidMEDLINE:17464999
dc.identifier.urihttps://doi.org/10.1002/hep.21616
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/79445
dc.identifier.wosidWOS:000246187700021
dc.information.autorucMedicina;Miquel J;S/I;72216
dc.information.autorucMedicina;Nervi F;S/I;99156
dc.information.autorucMedicina;Zanlungo S;S/I;72650
dc.issue.numero5
dc.language.isoen
dc.nota.accesoContenido parcial
dc.pagina.final1266
dc.pagina.inicio1261
dc.publisherJOHN WILEY & SONS INC
dc.revistaHEPATOLOGY
dc.rightsacceso restringido
dc.subjectLOW-DENSITY LIPOPROTEIN
dc.subjectAPOLIPOPROTEIN-B
dc.subjectNUCLEAR RECEPTORS
dc.subjectCHOLESTEROL-METABOLISM
dc.subjectLIPID-METABOLISM
dc.subjectGENE-EXPRESSION
dc.subjectMOLECULAR-BASIS
dc.subjectIN-VIVO
dc.subjectSECRETION
dc.subjectHYPERTRIGLYCERIDEMIA
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleIncreased activity of hepatic microsomal triglyceride transfer protein and bile acid synthesis in gallstone disease
dc.typeartículo
dc.volumen45
sipa.codpersvinculados72216
sipa.codpersvinculados99156
sipa.codpersvinculados72650
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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