| Deficiency of Niemann-Pick C1 protein protects against diet-induced gallstone formation in mice. | |
| | |
MedLine Citation:
|
PMID: 20408952 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
María Gabriela Morales; Ludwig Amigo; Elisa Balboa; Mariana Acuña; Juan Castro; Héctor Molina; Juan Francisco Miquel; Flavio Nervi; Attilio Rigotti; Silvana Zanlungo |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-08 |
Journal Detail:
|
Title: Liver international : official journal of the International Association for the Study of the Liver Volume: 30 ISSN: 1478-3231 ISO Abbreviation: Liver Int. Publication Date: 2010 Jul |
Date Detail:
|
Created Date: 2010-07-13 Completed Date: 2010-10-26 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101160857 Medline TA: Liver Int Country: England |
Other Details:
|
Languages: eng Pagination: 887-97 Citation Subset: IM |
Affiliation:
|
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
ATP-Binding Cassette Transporters
/
genetics Animals Bile / metabolism* Biological Transport Cholesterol 7-alpha-Hydroxylase / genetics Cholesterol, Dietary / metabolism* Cholic Acid Disease Models, Animal Gallstones / chemically induced, genetics, metabolism, prevention & control* Gene Expression Regulation Hydroxymethylglutaryl CoA Reductases / genetics Liver / metabolism* Male Mice Mice, Inbred BALB C Mice, Knockout Proteins / genetics, metabolism* RNA, Messenger / metabolism Receptors, LDL / genetics Sterol Regulatory Element Binding Protein 2 / genetics Vesicular Transport Proteins / genetics |
| Chemical | |
Reg. No./Substance:
|
0/ATP-Binding Cassette Transporters; 0/Cholesterol, Dietary; 0/Npc1 protein, mouse; 0/Npc2 protein, mouse; 0/Proteins; 0/RNA, Messenger; 0/Receptors, LDL; 0/Srebf2 protein, mouse; 0/Sterol Regulatory Element Binding Protein 2; 0/Vesicular Transport Proteins; 81-25-4/Cholic Acid; EC 1.1.1.-/Hydroxymethylglutaryl CoA Reductases; EC 1.14.13.17/Cholesterol 7-alpha-Hydroxylase; EC 1.14.13.17/cytochrome P450 7A1, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Medical and psychiatric outcomes for patients transplanted for acetaminophen-induced acute liver fai...
Next Document: Apoptosis is associated with CD36/fatty acid translocase upregulation in non-alcoholic steatohepatit...