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Journal of Lipid Research, Vol 31, 985-994, Copyright © 1990 by Lipid Research, Inc.
MR Soma, JD Morrisett, AM Gotto Jr, DS Loose-Mitchell, JA Poorman, SA Smith and ML Overturf
We have previously described a colony of New Zealand White rabbits that are
resistant to hypercholesterolemia when fed a cholesterol-enriched diet. The
present studies used skin fibroblasts obtained from normal and
hypercholesterolemia-resistant rabbits to investigate cholesterol
metabolism and lipid composition in vitro. The lipid compositions of the
two cell lines after incubation in either fetal calf serum or
lipoprotein-deficient serum were similar. The conversion of radiolabeled
acetate into sterol and phospholipids was higher in resistant fibroblasts
than in normal fibroblasts. In contrast, incorporation of radiolabeled
oleic acid into cholesteryl ester was significantly lower in resistant
fibroblasts than in normal cells. In parallel experiments, the
3-hydroxy-3-methylglutaryl coenzyme A reductase activity was higher and
acyl-coenzyme A:cholesterol acyltransferase activity was lower in resistant
cells compared to normal cells. Furthermore, binding, uptake, and
degradation of normal rabbit 125I-labeled LDL (low density lipoproteins)
were 30% higher in resistant than in normal fibroblasts. These observations
are consistent with results from previous studies of cholesterol metabolism
in the liver membranes of these rabbits. The results indicate that
extrahepatic cells (such as fibroblasts) from the resistant rabbit exhibit
the same altered cholesterol metabolism as that found in the hepatic
tissues of these rabbits. These studies suggest that the resistant rabbit
may provide an in vivo and in vitro system for studying the mechanisms by
which some individuals of a species can minimize the effect of dietary
cholesterol on the development of hypercholesterolemia and atherosclerosis.
ARTICLES
Cholesterol metabolism in fibroblasts from rabbits resistant to diet- induced hypercholesterolemia
Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030.
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