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Phytosterol feeding causes toxicity in ABCG5/G8 knockout mice.


ABSTRACT: Plant sterols, or phytosterols, are very similar in structure to cholesterol and are abundant in typical diets. The reason for poor absorption of plant sterols by the body is still unknown. Mutations in the ABC transporters G5 and G8 are known to cause an accumulation of plant sterols in blood and tissues (sitosterolemia). To determine the significance of phytosterol exclusion from the body, we fed wild-type and ABCG5/G8 knockout mice a diet enriched with plant sterols. The high-phytosterol diet was extremely toxic to the ABCG5/G8 knockout mice but had no adverse effects on wild-type mice. ABCG5/G8 knockout mice died prematurely and developed a phenotype that included high levels of plant sterols in many tissues, liver abnormalities, and severe cardiac lesions. This study is the first to report such toxic effects of phytosterol accumulation in ABCG5/G8 knockout mice. We believe these new data support the conclusion that plant sterols are excluded from the body because they are toxic when present at high levels.

SUBMITTER: McDaniel AL 

PROVIDER: S-EPMC3620394 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Phytosterol feeding causes toxicity in ABCG5/G8 knockout mice.

McDaniel Allison L AL   Alger Heather M HM   Sawyer Janet K JK   Kelley Kathryn L KL   Kock Nancy D ND   Brown J Mark JM   Temel Ryan E RE   Rudel Lawrence L LL  

The American journal of pathology 20130201 4


Plant sterols, or phytosterols, are very similar in structure to cholesterol and are abundant in typical diets. The reason for poor absorption of plant sterols by the body is still unknown. Mutations in the ABC transporters G5 and G8 are known to cause an accumulation of plant sterols in blood and tissues (sitosterolemia). To determine the significance of phytosterol exclusion from the body, we fed wild-type and ABCG5/G8 knockout mice a diet enriched with plant sterols. The high-phytosterol diet  ...[more]

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