Hepatic cholesterol and bile acid synthesis in Japanese patients with cholesterol gallstones |
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Authors: | Akira Honda Tadashi Yoshida Naomi Tanaka Yasushi Matsuzaki Bingfang He Toshiaki Osuga MD Nobuaki Kobayashi Kazue Ozawa |
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Institution: | 1. Department of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan 3. First Department of Surgery, Ehime University School of Medicine, Ehime, Japan 4. Second Department of Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan
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Abstract: | In Japan the composition of gallstones is changing rapidly from the once-predominant brownpigment stones to cholesterol ones.
The present work was undertaken to clarify the mechanism of cholesterol supersaturated bile production in Japanese patients
with cholesterol gallstones. In 26 non-obese and normolipidemic patients (11 with cholesterol gallstones, 8 with black- or
brown-pigment gallstones, 7 without gallstones) a liver biopsy and hepatic bile were surgically obtained under standardized
conditions. The cholesterol saturation of hepatic bile was significantly higher in cholesterol gallstone patients than in
gallstone-free controls (195 ±10 vs. 146 ±8%, respectively; P < 0.01). The microsomal activities of 3-hydroxy-3-methylglutaryl
coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for cholesterol synthesis, cholesterol 7 α-hydroxylase, the rate-limiting
enzyme for bile acid synthesis, and 7 α-hydroxy-4-cholesten-3-one 12 α-hydroxylase (12 α-hydroxylase), the rate-limiting enzyme
for cholic acid synthesis, were assayed simultaneously in the same subjects. There were positive correlations between HMG-CoA
reductase and cholesterol 7 α-hydroxylase activities (Rs = 0.62, P < 0.005), and between cholesterol 7 α-hydroxylase and 12
α-hydroxylase activities (Rs = 0.44, P < 0.05) in all subjects, irrespective of the existence of gallstones. The activities
of the three rate-limiting enzymes did not differ significantly among the three groups (cholesterol stone, pigment stone and
stone-free). In conclusion, the cholesterol supersaturation of hepatic bile in nonobese and normolipidemic Japanese patients
with cholesterol gallstones does not result from an increased hepatic cholesterol synthesis or a decreased bile acid synthesis.
This study was supported in part by a Grant-in-Aid for Scientific Research (No. 02454226) from the Ministry of Education,
Science and Culture of Japan, and a grant from University of Tsukuba Project Research. |
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Keywords: | 3-hydroxy-3-methylglutaryl coenzyme A reductase Cholesterol 7α -hydroxylase 12α -hydroxylase Gallstone disease |
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