|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1997 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1996 : ¥1,300,000 (Direct Cost : ¥1,300,000)
The incidence of cholesterol (CH) gallstone in Japan has dramatically increased in the past 50 years, during which intake of fish oil or n-3 polyunsaturated fatty acids (PUFA) has sharply declined. We aimed to clarify both in vivo and in vitro our hypothesis that eicosapentaenoic acid (EPA), a n-3 PUFA,might have a preventive effect on CH gallstone. The effect of EPA was compared with other fatty acids or bezafibrate in hamsters fed CH-rich diet. It was revealed that among various fatty acids only EPA inhibits the CH crystallization and gallstone formation in the hamster. This was accompanied by both increased total concentration and altered fatty acid composition (an increased EPA and decreased linoleic acid and arachidonic acid) of biliary phospholipids. How these changes in biliary lipids relate to the preventive effects was further studied in vitro. In the model bile system, increases in phosphatidylcholine (PC) that contains either EPA (16 : 0-20 : 5 PC), linoleic acid (16 : 0-18 : 2 PC), or arachidonic acid (16 : 0-20 : 4 PC) all decreased the vesicular CH saturation and similarly exerted potent and dose-dependent inhibitory effect on CH crystallization. These effects were clearly stronger than bile acids. Finally, in a culture system of gallbladder epithelia, EPA significantly inhibited the arachidonic acid-induced mucus glycoprotein secretion. The dual inhibitory effects of EPA on the two key pathogenetic factors (CH crystallization and mucus glycoprotein secretion) suggest critical roles of the n-3 PUFA in the formation and prevention of CH gallstone disease.