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Volume 270,
Number 10,
Issue of March 10, 1995 pp. 5381-5387
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
Regulation of
Hepatic 7 -Hydroxylase Expression and Response to Dietary
Cholesterol in the Rat and Hamster
(Received for publication, September 13, 1994; and in revised form, December 16, 1994)
Jay D.
Horton ,
Jennifer A.
Cuthbert,
David
K.
Spady
Although dietary cholesterol raises plasma total and low density
lipoprotein (LDL) cholesterol concentrations, the response to a given
intake of cholesterol varies enormously among different species and
even among individuals of the same species. The mechanisms responsible
for differing sensitivity to dietary cholesterol were examined by
comparing the rat, which is able to adapt to large fluctuations in
sterol intake or loss with little change in plasma LDL levels, with the
hamster, where changes in sterol balance strongly influence plasma LDL
concentrations. When fed the same cholesterol-free diet, hepatic
7 -hydroxylase activity was 16-fold higher in the rat than in the
hamster. As a consequence, rates of hepatic cholesterol synthesis were
20-fold higher in the rat than in the hamster. In both species, hepatic
cholesterol synthesis was suppressed >90% in response to increasing
loads of dietary cholesterol. However, the quantitative importance of
this adaptive mechanism was much greater in the rat since the absolute
reduction in hepatic cholesterol synthesis in the rat (2,110 nmol/h/g)
was much larger than in the hamster (103 nmol/h/g). In the rat, the
high basal level of 7 -hydroxylase expression was further induced
by substrate (cholesterol) allowing these animals to convert excess
dietary cholesterol to bile acids efficiently. In contrast, the low
basal level of enzyme expression in the hamster was not induced by
dietary cholesterol. Thus, the low basal rates of bile acid and
cholesterol synthesis coupled with a lack of 7 -hydroxylase
induction by cholesterol render the hamster much more sensitive than
the rat to the cholesterolemic effects of dietary cholesterol.

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Copyright © 1995 by the American Society for Biochemistry and Molecular Biology.
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