Bile acid synthesis in humans has a rapid diurnal variation that is asynchronous with cholesterol synthesis
Bile acid synthesis in humans has a rapid diurnal variation that is asynchronous with cholesterol synthesis
复制标题
DOI：
10.1053/j.gastro.2005.09.009
复制
发表时间：
2005-11-01
期刊：
影响因子：
29.4
通讯作者：
Rudling, M
中科院分区：
文献类型：
--
作者：
Gälman, C;Angelin, B;Rudling, M
背景和目的：肝脏将胆固醇转化为胆汁酸是体内胆固醇稳态的重要调节剂。在啮齿类动物中，胆固醇和胆汁酸的合成都有明显的昼夜节律，在午夜同步达到峰值。这项研究的目的是确定健康人类是否也存在这种昼夜节律。方法：在标准化饮食条件下，每隔 90 分钟测定 8 名人类志愿者的血清水平，其中监测胆汁酸生物合成的标记物 7-α-羟基-4-胆甾烯-3-酮 (C4) 和反映胆固醇合成的滑甾醇的血清水平。结果：血清 C4 在 24 小时内显示出 2 个不同的峰值（比基线高 2 至 4 倍），第一个出现在下午 1:00，第二个出现在晚上 9:00。夜间，C4 水平下降，第二天早上恢复到基线水平。相比之下，血清拉松甾醇水平在夜间（午夜至凌晨 4:00）达到峰值。 C4 的昼夜变化与血清脂质变化或餐后血清胆汁酸增加不同步，并且在胆囊切除受试者中保持不变。结论：人体胆汁酸合成具有昼夜节律，白天有2个峰值，这与胆固醇合成的昼夜节律相反。这与啮齿动物的模式完全不同，表明胆固醇稳态调节中存在重要的物种变异。
Background & Aims: The conversion of cholesterol to bile acids by the liver is an important regulator of body cholesterol homeostasis. In rodents, both cholesterol and bile acid synthesis have marked diurnal rhythms that peak synchronously at midnight. The aim of this study was to establish whether such diurnal rhythms are also present in healthy humans. Methods: Serum levels of the markers 7 alpha-hydroxy-4-cholesten-3-one (C4) monitoring bile acid biosynthesis and lathosterol reflecting cholesterol synthesis were determined at 90-minute intervals in 8 human volunteers during standardized dietary conditions. Results: Serum C4 showed 2 distinct peaks (2- to 4-fold above baseline) during a 24-hour period, the first at 1:00 PM and the second at 9:00 Pm. During the night, C4 levels declined, and they returned to baseline levels the next morning. In contrast, serum lathosterol levels peaked at night, between midnight and 4:00 AM. The diurnal changes of C4 were not synchronous with serum lipid changes or with the postprandial increase in serum bile acids and were maintained in cholecystectomized subjects. Conclusions: Bile acid synthesis in humans has a diurnal rhythm, with 2 peaks during the daytime, that is opposite from the circadian rhythm of cholesterol synthesis. This is completely different from the pattern in rodents and indicates the presence of an important species variation in the regulation of cholesterol homeostasis.