title: 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.
authors: Section on Lipid Sciences, Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors: Allison L
authors: AL
authors: McDaniel
authors: Heather M
authors: HM
authors: Alger
authors: Janet K
authors: JK
authors: Sawyer
authors: Kathryn L
authors: KL
authors: Kelley
authors: Nancy D
authors: ND
authors: Kock
authors: J Mark
authors: JM
authors: Brown
authors: Ryan E
authors: RE
authors: Temel
authors: Lawrence L
authors: LL
authors: Rudel
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D004032:Diet; D004912:Erythrocytes / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006529:Hepatomegaly / Q000097:blood / Q000235:genetics / Q000473:pathology; D008074:Lipoproteins / Q000172:deficiency* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010840:Phytosterols / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013163:Splenomegaly / Q000097:blood / Q000235:genetics / Q000473:pathology; D015430:Weight Gain / Q000187:drug effects
chemical_list: C462600:ABCG5 protein, mouse; C462601:ABCG8 protein, mouse; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D008074:Lipoproteins; D010840:Phytosterols
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