Abstract
In order to elucidate the mechanism of xanthoma formation in cerebrotendinous xanthomatosis, mice were fed for 32 weeks with a diet rich in 5α-cholestan-3β-ol (cholestanol) (1%, w/w). The concentrations of sterols in the serum, liver, and cerebellum were determined using high performance liquid chromatography. In the cholestanol-fed mice, the cholestanol concentrations in the serum and liver reached maxima in the first 2 to 4 weeks; the levels were about 30- to 100-fold higher than in the control diet mice. The cholestanol concentrations declined thereafter, finally to 50-60% of the maxima. Cholesterol concentrations were slightly lower in the cholestanol-fed mice throughout the experiments than in the control diet mice. On the other hand, the levels of cholestanol in the cerebellum increased almost linearly in parallel to the feeding time, and no decline was observed. These results suggest that the capacity of the liver to remove or degrade cholestanol was increased by long-term intake of this compound, whereas the cerebellum had no such feed-back regulation. Histological examinations using an electron microscope revealed the enlargement of lysosomal granules in the liver of the cholestanol-fed mice.
