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Niemann‐Pick C2 Protein Expression Regulates Lithogenic Diet‐Induced Gallstone Formation and Dietary Cholesterol Metabolism in Mice
Author(s) -
Balboa Elisa,
Morales Gabriela,
Aylwin Paula,
Carrasco Gonzalo,
Amigo Ludwig,
Castro Juan,
Rigotti Attilio,
Zanlungo Silvana
Publication year - 2012
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-011-3625-2
Subject(s) - cholesterol , reverse cholesterol transport , medicine , phospholipid , endocrinology , metabolism , clinical chemistry , gallbladder , cyp27a1 , chemistry , cholesterol 7 alpha hydroxylase , biology , lipoprotein , biochemistry , membrane
Abstract Niemann‐Pick C2 protein (NPC2) is a lysosomal soluble protein that is highly expressed in the liver; it binds to cholesterol and is involved in intracellular cholesterol trafficking, allowing the exit of lysosomal cholesterol obtained via the lipoprotein endocytic pathway. Thus, this protein may play an important role in controlling hepatic cholesterol transport and metabolism. The aim of this work was to study the relevance of NPC2 protein expression in hepatic cholesterol metabolism, biliary lipid secretion and gallstone formation by comparing NPC2 hypomorph [NPC2 (h/h)] and wild‐type mice fed control, 2% cholesterol, and lithogenic diets. NPC2 (h/h) mice exhibited resistance to a diet‐induced increase in plasma cholesterol levels. When consuming the chow diet, we observed increased biliary cholesterol and phospholipid secretions in NPC2 (h/h) mice. When fed the 2% cholesterol diet, NPC2 (h/h) mice exhibited low and high gallbladder bile cholesterol and phospholipid concentrations, respectively. NPC2 (h/h) mice fed with the lithogenic diet showed reduced biliary cholesterol secretion, gallbladder bile cholesterol saturation, and cholesterol crystal and gallstone formation. This work indicates that hepatic NPC2 expression is an important factor in the regulation of diet‐derived cholesterol metabolism and disposal as well as in diet‐induced cholesterol gallstone formation in mice.