1992 Fiscal Year Final Research Report Summary
Cholesterol and bile acid metabolism in cholesterol gallstone disease
| Project/Area Number |
02454226
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Tsukuba University |
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Principal Investigator |
OSUGA Toshiaki Tsukuba University, Clinical Medicine, Professor, 臨床医学系, 教授 (20010481)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUZAKI Yasusi Tsukuba University, Clinical Medicine, Lecturer, 臨床医学系, 講師 (50209532)
TANAKA Naomi Tsukuba University, Clinical Medicine, Lecturer, 臨床医学系, 講師 (60111530)
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| Project Period (FY) |
1990 – 1992
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| Keywords | Gallstone disease / Cholesterol / Bile acid / HMG-CoA reductase / Cholesterol 7alpha-hydroxylase / Gas chromatography-mass spectrometry |
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| Research Abstract |
The present work was undertaken to clarify the mechanism of cholesterol supersaturated bile production in Japanese patients with cholesterol gallstones. The cholesterol saturation of hepatic bile was significantly higher in cholesterol gallstone patients than in gallstone-free controls. Hepatic microsomal activities of HMG-CoA reductase, cholesterol 7alpha-hydroxylase and 7alpha-hydroxy-4-cholesten-3-one 12alpha-hydroxylase did not differ significantly between the two groups. Patients with cholesterol gallstone disease have a reduced pool of bile acids. Overly sensitive feedback inhibition of bile acid synthesis has been postulated to explain the size reduction. To clarify the hepatic defect in feedback regulation, hepatic bile acid concentration was determined in our patients. If the overly sensitive feedback inhibition existed truly in our gallstone patients, decreased concentration of hepatic bile acids and normal or decreased activity of cholesterol 7alpha-hydroxylase would have been expected. However, patients with cholesterol gallstones had significantly higher total, chenodeoxycholic, deoxycholic, and ursodeoxycholic acid concentrations than patients without gallstones. The accumulation of bile acids in the liver of patients with gallstones is not due to an increased hepatic bile acid synthesis. It is probably related to the inability of the liver to excrete bile acids. In conclusion, we found no evidence of an increased hepatic cholesterol synthesis or a decreased bile acid synthesis in Japanese patients with cholesterol gallstones compared to stone-free controls. However, there is a possibility that the excessive feedback inhibition of cholesterol 7alpha-hydroxylase is induced by an inappropriate increase of hepatic bile acid concentration in cholesterol gallstone patients rather than by overly sensitive feedback inhibition.
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