Alterations in cholesterol metabolism in cultured fibroblasts from patients with Niemann‐Pick disease type C

Abstract

Summary: Cholesterol synthesis, esterification and efflux were investigated in cultured fibroblasts from patients with Niemann‐Pick disease type C. Sterol synthesis from sodium acetate was markedly increased in the two Niemann‐Pick disease type C strains as compared to controls, either in the presence or absence of exogenous cholesterol supply by low‐density lipoproteins. By contrast, cholesterol esterification was about 2–3‐fold reduced when measured by oleic acid incorporation into cholesteryl esters and 10–15‐fold reduced when measured with labelled free cholesterol as precursor, although acylcoenzyme‐A: cholesterol acyltransferase activity was normal when studiedin vitro on cell homogenates. Chase experiments with¹⁴C‐cholesterol demonstrated that the rate of cholesterol efflux was decreased by about 3–4‐fold in fibroblasts from patients with Niemann‐Pick disease type C. These results provide further evidence for alterations of sterol metabolism in Niemann‐Pick disease type C and support the hypothesis of a trapping of exogenous cholesterol, which cannot enter the regulatory intracellular pools.