Depletion of high-density lipoprotein and appearance of triglyceride-rich low-density lipoprotein in a Japanese patient with FIC1 deficiency manifesting benign recurrent intrahepatic cholestasis
Depletion of high-density lipoprotein and appearance of triglyceride-rich low-density lipoprotein in a Japanese patient with FIC1 deficiency manifesting benign recurrent intrahepatic cholestasis
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DOI：
10.1097/mpg.0b013e3180331df9
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发表时间：
2007-07-01
影响因子：
2.9
通讯作者：
Kobayashi, Kunihiko
中科院分区：
文献类型：
--
作者：
Nagasaka, Hironori;Chiba, Hitoshi;Kobayashi, Kunihiko
目的：ATP8B1基因突变所致的Fic I缺乏症的脂蛋白代谢一直没有得到充分的研究。为了解FIC1缺乏所致良性复发性肝内胆汁淤积症(BRIC)患者脂蛋白代谢的详细情况。方法：对一例日本BRIC患者在一次胆汁淤积过程中，对其脂蛋白谱和主要脂蛋白调节因子如卵磷脂：胆固醇酰基转移酶(LCAT)、肝甘油三酯脂肪酶(HTGL)、脂蛋白脂肪酶和胆固醇酯转移蛋白进行了系列检测。还检测了抑制高密度脂蛋白(高密度脂蛋白)生成的法尼类X受体(FXR)在肝脏中的表达。结果：在整个研究过程中，没有观察到高胆固醇血症和脂蛋白X积聚。当胆汁淤积严重时，富含甘油三酯的低密度脂蛋白(LDL)占血浆脂蛋白的大部分，而高密度脂蛋白(HDLE)几乎检测不到。同时，所有调节因子的活性均降低，同时肝脏蛋白质合成的血清参数也降低。特别是，LCAT和HTGL活性的抑制是严重的，并极大地促进了富含甘油三酯的低密度脂蛋白的出现。随着胆汁淤积的改善，随着LCAT和HTGL活性的恢复，这种低密度脂蛋白逐渐转变为正常的低密度脂蛋白。所有调节器在最后1-2个月的活动都是正常的，但高密度脂蛋白仍然耗尽。与对照组相比，他的肝脏表现出低水平的FXR表达。结论：在本研究中，患者出现富含甘油三酯的低密度脂蛋白，这是由于LCAT和HTGL活性的抑制以及高密度脂蛋白的耗竭，这不能用脂蛋白调节剂或FXR来解释。
Objective: Lipoprotein metabolism in FIC I deficiency due to ATP8B1 mutations has never been studied sufficiently. This study was performed to investigate the detailed lipoprotein metabolism in benign recurrent intrahepatic cholestasis (BRIC) caused by FIC1 deficiency.Patients and Methods: Lipoprotein profile and major lipoprotein regulators such as lecithin: cholesterol acyltransferase (LCAT), hepatic triglyceride lipase (HTGL), lipoprotein lipase, and cholesteryl ester transfer protein in a Japanese patient with BRIC were serially examined during a bout of cholestasis. Liver expression of farnesoid X receptor (FXR), which suppresses high-density lipoprotein (HDL) generation., was also examined.Results: Hypercholesterolemia and lipoprotein X accumulation were never observed throughout this study. When the cholestasis was severe, triglyceride-rich low-density lipoprotem (LDL) accounted for most of the plasma lipoproteins whereas HDL was hardly detectable. Concurrently, activities of all regulators were decreased, together with decreases of the serum parameter for liver protein synthesis. In particular, suppressions of LCAT and HTGL activities were severe and greatly contributed to the appearance of triglyceride-rich LDL. As the cholestasis improved, this LDL gradually transformed into normal LDL with the recoveries of LCAT and HTGL activities. The activities of all regulators for the last I to 2 months were normal but HDL remained depleted. His liver showed low FXR expression compared with control livers.Conclusions: The present study showed an appearance of triglyceride-rich LDL due to suppressions of LCAT and HTGL activities and a depletion of HDL that is not able to be explained by lipoprotein regulators or FXR in our patient.