Hepatobiliary cholesterol transport as not impaired in Abca1-null mice lacking HDL
Hepatobiliary cholesterol transport as not impaired in Abca1-null mice lacking HDL
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DOI：
10.1172/jci12473
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发表时间：
2001-09-01
影响因子：
15.9
通讯作者：
Kuipers, F
中科院分区：
文献类型：
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作者：
Groen, AK;Bloks, VW;Kuipers, F
ABC转运蛋白ABCA 1调节HDL水平，并被认为是控制胆固醇从外周向肝脏逆向转运的第一步。为了验证这一概念，我们研究了ABCA 1缺乏对小鼠肝脏代谢和胆固醇肝胆流量的影响。在具有DBA背景的Abca 1（-/-）、Abca 1（+/-）和Abca 1（+/+）小鼠中测定肝脏脂质含量和胆汁分泌率，这些小鼠喂食标准食物或高脂肪、高胆固醇饮食。Abca 1（-/-）小鼠的肝脏胆固醇和磷脂含量与Abca 1（+/-）和Abca 1（+/+）小鼠的肝脏胆固醇和磷脂含量在两种饲料中均无法区分。尽管缺乏HDL，但Abca 1（-/-）小鼠胆固醇、胆汁盐和磷脂的胆汁分泌率未受损。无论是控制胆固醇代谢关键步骤的基因的肝脏表达水平，还是从头合成胆汁胆固醇和胆汁盐的贡献，都不受Abca基因型的影响。最后，中性和酸性固醇的粪便排泄在所有组中相似。我们的结论是，血浆HDL水平和ABCA 1活性不控制净胆固醇从外周经肝脏转运到胆汁中，这表明HDL在胆固醇逆向转运中的重要性需要重新评估。
The ABC transporter ABCA1 regulates HDL levels and is considered to control the first step of reverse cholesterol transport from the periphery to the liver. To test this concept, we studied the effect of ABCA1 deficiency on hepatic metabolism and hepatobiliary flux of cholesterol in mice. Hepatic lipid contents and biliary secretion rates were determined in Abca1(-/-), Abca1(+/-), and Abca1(+/+) mice with a DBA background that were fed either standard chow or a high-fat, high-cholesterol diet. Hepatic cholesterol and phospholipid contents in Abca1(-/-) mice were indistinguishable from those in Abca1(+/-) and Abca1(+/+) mice on both diets. In spite of the absence of HDL, biliary secretion rates of cholesterol, bile salts, and phospholipid were unimpaired in Abca1(-/-) mice. Neither the hepatic expression levels of genes controlling key steps in cholesterol metabolism nor the contribution of de novo synthesis to biliary cholesterol and bile salts were affected by Abca genotype. Finally, fecal excretion of neutral and acidic sterols was similar in all groups. We conclude that plasma HDL levels and ABCA1 activity do not control net cholesterol transport from the periphery via the liver into the bile, indicating that the importance of HDL in reverse cholesterol transport requires re-evaluation.