Deficiency of Niemann-Pick C1 protein protects against diet-induced gallstone formation in mice.
Liver Int
; 30(6): 887-97, 2010 Jul.
Article
em En
| MEDLINE
| ID: mdl-20408952
BACKGROUND/AIMS: Receptor-mediated endocytosis is a critical cellular mechanism for the uptake of lipoprotein cholesterol in the liver. Because Niemann-Pick C1 (NPC1) protein is a key component for the intracellular distribution of cholesterol originating from lipoprotein endocytosis, it may play an important role in controlling biliary cholesterol secretion and gallstone formation induced by a lithogenic diet. METHODS: We studied biliary cholesterol secretion, gallbladder lipid composition and gallstone formation in NPC1-deficient mice fed a low-fat lithogenic diet (1.5% cholesterol and 0.5% cholic acid) compared with control animals under the same diet. RESULTS: The lipid secretion response to the lithogenic diet was impaired in NPC1 (-/-) mice, leading to a decreased cholesterol output and an increased hepatic cholesterol concentration compared with the lithogenic diet-fed wild-type mice. A decreased cholesterol saturation index was found in the gallbladder bile of NPC1 (+/-) and (-/-) mice after lithogenic diet feeding. Consequently, mice with a partial or a total deficiency of NPC1 had a drastically lower frequency of gallbladder cholesterol crystals and a reduced prevalence of gallstones. CONCLUSION: Hepatic NPC1 expression is an important factor for regulating the biliary secretion of diet-derived cholesterol as well as for diet-induced cholesterol gallstone formation in mice.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bile
/
Colesterol na Dieta
/
Proteínas
/
Cálculos Biliares
/
Fígado
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Liver Int
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Chile
País de publicação:
Estados Unidos