| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2006: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2005: ¥9,900,000 (Direct Cost: ¥9,900,000)
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| Research Abstract |
It has been thought that stroke-prone spontaneously hypertensive rats (SHRSP) deposit plant sterols in the body, because they have a missense mutation in ATP-binding cassette transporter (ABC) G5 and hence, ABCG5/ABCG8 do not fully function. However, in the present study, intestinal absorption of plant sterols in SHRSP was the same as that in Wistar rats. Therefore, it is thought that difference in intestinal absorption of plant sterols is not a major cause in their deposition in SHRSP. ABCG5/ABCG8 also express in the liver. We speculated that biliary excretion of plant sterols was suppressed in SHRSP because of the malfunction of ABCG5/ABCG8. After SHRSP and Wistar rats were fed a plant sterol diet for 1 week, we measured excretion amounts of plant sterols in bile for 3 hrs. The amount was higher in SHRSP than in Wistar rats. In a separate study, rats were intravenously injected radiolabeled sitosterol and biliary excretion of the radioactivity was measured for 3 hrs. The excretion of
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radiolabeled sitosterol was lower in SHRSP only at 0-1 hr than in Wistar rats. The results suggest that biliary excretion of sitosterol may be suppressed at an early stage. Long-term collection of bile might be unphysiological and the data at an early stage of bile collection may be in physiological condition. Further studies are necessary.
Dietary soy protein isolate, compared to casein, increased hepatic ABCG5/ABCG8 mRNA expression in rats. Hepatic CYP7A1 mRNA was also increased, but small heterodimer partner (SHP) mRNA was decreased in soy protein isolate. The results suggest that Liver receptor homologue-1(LRH-1) is activated by the reduction of SHP and hence, CYP7A1 is activated. It was recently reported that ABCG5 and ABCG8 are also target genes of LRH-1. Therefore, it is thought that the activation of LRH-1 induced increase of ABCG5 and ABCG8 mRNA. Biliary excretion of cholesterol was higher in rats fed soy protein isolate than in those fed casein. It is suggested that this increase is induced by the increase of ABCG5 and ABCG8. Less
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