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.
OBJECTIVE
Lipoprotein metabolism in FIC1 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.


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 lipoprotein (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 1 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.
Nagasaka
Hironori
H
Division of Metabolism, Chiba Children's Hospital, Heta Cho, Midori-Ku, Chiba, Japan. nagasa-hirono@k2.dion.ne.jp
Chiba
Hitoshi
H
Hui
Shu-Ping
SP
Takikawa
Hajime
H
Miida
Takashi
T
Takayanagi
Masaki
M
Yorifuji
Tohru
T
Hasegawa
Makoto
M
Ota
Akemi
A
Hirano
Ken-ichi
K
Kikuchi
Hideaki
H
Tsukahara
Hirokazu
H
Kobayashi
Kunihiko
K
D000251:Adenosine Triphosphatases / Q000172:deficiency*; D000328:Adult; D001057:Apolipoproteins E / Q000097:blood; D002780:Cholestasis, Intrahepatic / Q000097:blood* / Q000209:etiology; D008076:Cholesterol, HDL / Q000097:blood; D006801:Humans; D006932:Hyperbilirubinemia / Q000209:etiology; D007564:Japan; D008075:Lipoproteins, HDL / Q000097:blood* / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008297:Male; D010195:Pancreatitis / Q000097:blood / Q000209:etiology; D014176:Protein Biosynthesis; D012008:Recurrence; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human