Inactivation of hepatic microsomal triglyceride transfer protein protects mice from diet-induced gallstones

dc.contributor.authorAmigo, Ludwig
dc.contributor.authorCastro, Juan
dc.contributor.authorMiquel, Juan Francisco
dc.contributor.authorZanlungo, Silvana
dc.contributor.authorYoung, Stephen G.
dc.contributor.authorNervi, Flavio
dc.date.accessioned2024-01-10T13:13:45Z
dc.date.available2024-01-10T13:13:45Z
dc.date.issued2006
dc.description.abstractBackground & Aims: Microsomal triglyceride transfer protein (MTTP) is critical for the production of very-low-density lipoproteins (VLDL). The current studies were undertaken to examine the in vivo role of MTTP in hepatic cholesterol and fatty acid metabolism, as well as in biliary lipid secretion. We also tested whether MTTP plays a role in diet-induced cholelithiasis in mice. Methods: We used mice in which Mttp had been inactivated in the liver (Mttp(Delta/Delta) mice). We measured several parameters of cholesterol metabolism, fatty acid synthesis, and biliary lipid levels in mice fed a normal or a lithogenic diet. We also assessed the incidence of diet-associated gallstones. Results: Hepatic Mttp inactivation markedly decreased plasma triglyceride and cholesterol levels and increased biliary cholesterol and bile acid output. Hepatic cholesterogenesis and fatty acid synthesis were significantly decreased in Mttp(Delta/Delta), mice compared with control mice. The incidence of gallstones decreased from 90% in control mice to 33% in Mttp(Delta/Delta) mice after 8 weeks of a lithogenic diet (P < .0001). The mechanism of the protective effect appears to be increased biliary phospholipid output in Mttp(Delta/Delta) mice, leading to significant unsaturation of gallbladder bile. Conclusions: These results indicate that modulation of Map expression in the liver affects hepatic lipid svnthesis and storage as well as biliary lipid secretion. Our findings further indicate that inhibition of hepatic MTTP activity decreases the risk of experimental cholelithiasis by favoring phospholipid output into the bile.
dc.fechaingreso.objetodigital2024-04-25
dc.format.extent9 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1053/j.gastro.2006.08.029
dc.identifier.eissn1528-0012
dc.identifier.issn0016-5085
dc.identifier.pubmedidMEDLINE:17064699
dc.identifier.urihttps://doi.org/10.1053/j.gastro.2006.08.029
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/78335
dc.identifier.wosidWOS:000243031100030
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.numero6
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final1878
dc.pagina.inicio1870
dc.publisherW B SAUNDERS CO-ELSEVIER INC
dc.revistaGASTROENTEROLOGY
dc.rightsacceso restringido
dc.subjectBILIARY CHOLESTEROL SECRETION
dc.subjectLIPOPROTEINS
dc.subjectVLDL
dc.subjectTISSUE
dc.subjectLIVER
dc.subjectRATES
dc.subjectACID
dc.subjectOVEREXPRESSION
dc.subjectCIRCULATION
dc.subjectMETABOLISM
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleInactivation of hepatic microsomal triglyceride transfer protein protects mice from diet-induced gallstones
dc.typeartículo
dc.volumen131
sipa.codpersvinculados72216
sipa.codpersvinculados99156
sipa.codpersvinculados72650
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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