1) Carey MC: Textbook of gastroenterology (ed. by Bouchier IAD, et al), Bailliere Tindall, Eastbourne, pp 1389-1400, 1984 2) Dam H, Christensen F: Alimentary production of gallstones in hamsters. Acta Pathol Scand 30: 236-242, 1952 Microb 3) Wilgram GF, Kennedy EP: Intracellular distribution of some enzymes catalyzing reactions in the biosynthesis of complex lipids. J Biol Chem 238: 2615-2619, 1963 4) Brown MS, Goldstein JL, Dietschy JM: Active and inactive forms of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the liver of the rat. J Biol Chem 254: 5144-5149, 1979 5) Ogishima T, Okuda K: An improved method for assay of cholesterol 7a-hydroxylase activity. Anal Biochem 158: 228-232, 1986 7) Admirand WH, Small DM: The physicochemical basis of cholesterol gallstone formation in man. J Clin Invest 47: 1043-1052, 1968 8) Folch J, Lees M, Stanley GHS: A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226: 497-509, 1957 9) Spady DK, Turley SD, Dietschy JM: Rates of low density lipoprotein uptake and cholesterol synthesis are regulated indepnedently in the liver. J Lipid Res 26: 465-472, 1985 10) Spady DK, Stange EF, Dietschy JM, et al: Bile acdis regulate hepatic low density lipopro-

tein receptor activity in the hamster by altering cholesterol flux across the liver. Proc Natl Acad Sci USA 83: 1916-1920, 1986 11) Kamata T, Tanimura H, Murachi T, et al: Experimental study on hepatic 3-hydroxy-3- methylglutaryl-coa reductase activity in relation to the formation and disappearance of cholesterol gallstone in hamsters. J Appl Biochem 4: 72-80, 1982 12) Schoenfield LJ, Bonorris GG, Ganz P: Induced alterations in the rate-limiting enzymes of hepatic cholesterol and bile acid synthesis in the hamster. J Lab Clin Med 82: 858-868, 1973 13) Kajiyama G, Kubota S, Kawamoto T, et al: Lipid metabolism in the development of cholesterol gallstones in hamsters. Hiroshima J Med Sci 29: 133-141, 1980 14) Davis RA, Hyde PM, Schexnayder JA, et al: Bile acid secretion by cultured rat hepatocytes. Regulation by cholesterol availability. J Biol Chem 258: 3661-3667, 1983 15) Shefer S, Hauser S, Mosbach EH, et al: Feedback regulation of bile acid biosynthesis in the rat. J Lipid Res 10: 646-655, 1969 16) Shefer S, Hauser S, Mosbach EH, et al: Biochemical site of regulation of bile acid biosynthesis in the rat. J Lipid Res 11: 404-411, 1970 17) Ahlberg J, Angelin B, Einarsson K, et al: Hepatic cholesterol metabolism in normo- and hyper-lipidemic patients with cholesterol gallstones. J Lipid Res 20: 107-115, 1979 18) Angelin B, Einarsson K, Leijd B, et al: Bile acid kinetics in relation to endogenous tryglyceride metabolism in various types of hyperlipoproteinemia. J Lipid Res 19: 1004-1016, 1978 Bile acid and lipid metabolism in hamsters fed with high glucose diet -with special reference to a gallstone model animal with type IV hyperlipidemia- Kazunobu KOIDE, Yasuhiko HIRATA, Hiromasa OHTANI Harutoshi SASAKI, Shigeki MIZUNO, Susumu TAZUMA, Kouki TAKATA, Itaru HORIUCHI, Goro KAJIYAMA The metabolism of cholesterol and bile acids in the liver was investigated in hamsters fed with high glucose diet, as the experimental model of cholesterol gallstone often observed in human type IV hyperlipidemia. Glucose feeding induced augmentation of the activities of both hepaic HMG-CoA reductase, a rate limiting enzyme of cholesterol synthesis, and hepatic cholesterol 7a-hydroxylase, a rate limiting enzyme of bile acid synthesis. The activity of hepatic HMG-CoA reductase exceeded by far that of cholesterol 7a-hydroxylase after the second week of glucose feeding. The dissociation between the activities of both the hepatic enzymes seems to induce extreme increment of cholesterol secretion into bile. Total bile acids secretion into bile didn't increase, although the pool size of bile acids increased. As a result, it is concluded that the bile becomes supersaturated with cholesterol by glucose feeding and cholesterol gallstone is formed. * The First Department of Internal Medicine, Hiroshima University, School of Medicine (Hiroshima)