Research on regulation of absorption and metabolism of sterols by ABC transporters

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We found that SHRSP rats, which deposit plant sterols in their body, have a point mutation on ATP binding cassette transporter (ABC)G 5. ABCG5 and G8 form a heterodimer and have a function to excrete cholesterol and plant sterols from intestine and liver. Since the function of ABCG5 and G8 is insufficient in SHRSP rats, plant sterols may be deposited in their body. Expression of ABCG5 and G8 is regulated by liver X receptor. In the next study, LXR agonist was fed to SHRSP and normal rats together with plant sterols. Although expression of ABCG5 and G8 in the intestine of SHRSP and normal rats was increased by the feeding of LXR agonist, plant sterols in the liver of SHRSP rats were hardly reduced. In contrast, deposition of plant sterols in the liver of normal rats was reduced. The results strongly suggest that SHRSP rats can hardly excrete plant sterols from their body. Expression of ABCG5 and G8 in the liver was not stimulated by the feeding of LXR agonist in SHRSP rats. This may be one of the reasons by which plant sterols in the liver of SHRSP rats was not reduced by the feeding of LXR agonist.