PLX247810

GSE146522: To determine the effects of non-cholesterol based sterol enriched diets on liver gene expression

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Xenosterol accumulation in mice deficient in sterolin function leads to significant toxicity, with infertility, decreased body fat accumulation, macrothrombocytopenia, cardiac fibrosis and premature death. The predominant xenosterols are phytosterols derived from the diet which includes a mixture of sitosterol (typically 70%), campesterol (~20%) and stigmasterol (~5-10%), and ergosterol found in fungi. To delineate whether ergosterol or stigmasterol could accumulate in Abcg8 knockout mice and demonstrate any signs of xenosterol toxicity, we designed two diets with one supplemented with ergosterol (>98% purity) and other with stigmasterol (>80% purity) and fed them to Abcg8 knockout mice. Over a 12-week period, both male and female Abcg8 knockout mice fed with either of the diets gained normal amounts of weight, body fat, showed no disturbances in tail-cuff measured blood pressure, and plasma analyses showed no abnormalities of platelet counts or volumes, blood glucose, or plasma cholesterol. Fertility testing showed no abnormalities. While stigmasterol accumulation was observed in the both plasma and tissues, elevated levels of ergosterol was not observed in plasma. However, there was a dramatic increase in plasma brassicasterol, with levels reaching 80 mg/dL in plasma. Our data concludes that either stigmasterol or ergosterol or brassicasterol accumulations in Abcg8 Knockout Mice does not account for xenosterol toxicity. SOURCE: Shailendra PatelPatel University of Cincinnati