Title: Bile acids and FXR represses cholesterol 7A-hydroxylase (CYP7A1), sterol 12A-hydroxylase (CYP8B1) and sterol 27-hydroxylase (CYP27A1), but not oxysterol 7A-hydroxylase (CYP7B1) gene transcription
Abstract: The liver plays a critical role in the metabolism of lipoprotein cholesterol and is a key organ for cholesterol removal from the body.Although most of the cholesterol secreted into bile is normally derived from plasma lipoproteins, it is not certain the relative contribution from any particular hepatic lipoprotein metabolic pathway for biliary lipid secretion.The receptor-mediated endocytic pathway is one of the major mechanisms for uptake of lipoprotein cholesterol in the liver.Since Niemann-Pick C1 protein (NPC1) is a key component in the delivery of cholesterol obtained from lipoproteins by the endocytic pathway it may play a critical role in controlling biliary secretion of plasma lipoprotein-derived cholesterol.Aim: To analyze the relevance of the NPC1-dependent endocytic pathway for lipoproteins in the liver on the regulation of biliary lipid secretion in vivo.Methods: BALB/cnpcn;h NPCI-deficient mice (1 month old) were fed for 2 weeks with chow diet or with a high cholesterol diet and hepatic cholesterol content, bile flow and biliary lipid secretion were measured.Results: As excepted the liver from NPC1-deficient mice showed a higher content of unesterified cholesterol in comparison with control mice in chow diet (11.8 mglliver vs. 2.4 mg/liver), and this difference was even greater after feeding a high cholesterol-diet (37.9 mglliver vs. 3.1 mglliver).With regard to biliary lipid secretion, chow diet-fed NPCI-deficient mice exhibited a 1.7-fold increase in cholesterol output compared with control mice.During the high cholesterol-diet feeding period, cholesterol secretion increased by 3-fold in control mice, whereas no change was observed in affected mice.Surprisingly, bile salt secretion increased by 1.9-fold in NPCl-deficient after feeding a high cholesterol diet while it remained unchanged in control mice.Conclusion: These results show that hepatic NPC1 expression is an important factor for the regulation of biliary lipid secretion in mice during feeding either a cholesterol-poor chow diet or a cholesterol-rich diet.Further studies are required to elucidate the source of cholesterol, the metabolic pathways, and the cellular mechanisms involved in the NPCI-dependent changes observed in biliary lipid secretion.2355
Publication Year: 2000
Publication Date: 2000-04-01
Language: en
Type: article
Indexed In: ['crossref']
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Cited By Count: 4
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