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Journal of Lipid Research, Vol 27, 537-548, Copyright © 1986 by Lipid Research, Inc.
FL Johnson, J Babiak and LL Rudel
To determine whether altered hepatic secretion of HDL is part of the
mechanism by which polyunsaturated fat lowers plasma HDL concentration, we
have studied HDL secretion in the isolated perfused livers of African green
monkeys fed an atherogenic diet containing either safflower oil as the
polyunsaturated fat or butter as the saturated fat. During recirculating
perfusion with a lipoprotein-free medium, livers from safflower oil-fed
animals produced 21% less HDL mass on the average than those from
butter-fed animals. Newly secreted hepatic HDL were characterized after
their isolation and subfractionation by a combination of agarose column
chromatography and density gradient ultracentrifugation. In both diet
groups the HDL were heterogeneous in size, morphology, and composition and
consisted of discoidal particles ranging in diameter from greater than 200
A to as little as 50 A. Large, discoidal particles that were rich in apoE
and apoA-I were separated from small particles that were poor in apoE but
rich in apoA- I. All hepatic HDL subfractions contained only small amounts
of cholesteryl ester and triglyceride. The hepatic particles resembled in
composition and structure the large variety of HDL particles found in the
plasma of patients with the familial deficiency of lecithin:cholesterol
acyltransferase. Accordingly, perfusate LCAT activity was measured and
found to be 2% or less than that in monkey plasma. We conclude that the
perfused monkey liver produces a variety of nascent HDL that are relatively
unmodified by the post-secretory metabolic events which normally occur in
blood plasma in vivo, and that livers of polyunsaturated fat-fed monkeys
secrete fewer plasma HDL precursor particles than do those of saturated
fat-fed monkeys.
ARTICLES
High density lipoprotein accumulation in perfusates of isolated livers of African green monkeys. Effects of saturated versus polyunsaturated dietary fat
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