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Journal of Lipid Research, Vol 28, 32-41, Copyright © 1987 by Lipid Research, Inc.
Role of receptor-independent low density lipoprotein transport in the maintenance of tissue cholesterol balance in the normal and WHHL rabbit
DK Spady, M Huettinger, DW Bilheimer and JM Dietschy
These studies were undertaken to determine the role of receptor-
independent low density lipoprotein (LDL) transport in cholesterol balance
across individual tissues and the whole animal. Homologous LDL, which
measures total LDL transport, and methylated heterologous LDL, which
measures receptor-independent LDL uptake, were cleared from the plasma at
very different rates in the NZ control rabbit (3,900 and 1,010
microliter/hr per kg, respectively) whereas in the WHHL rabbit both
preparations were cleared at essentially the same rate (approximately 1,070
microliter/hr per kg). Receptor-independent LDL clearance was detected in
all tissues of the NZ control rabbit and these varied from 32 (spleen) to
less than 0.5 (skeletal muscle) microliter/hr per g. In contrast,
receptor-dependent LDL uptake was found in only about half of these same
organs. In the WHHL rabbit, the rates of receptor-independent LDL transport
were the same as in the NZ control rabbit, but no receptor-dependent uptake
was detected. Using these clearance values it was calculated that in the
control rabbit nearly 70% of LDL-cholesterol was removed from the plasma by
the liver and 89% of this was receptor-mediated. With loss of receptor
activity, however, the burden of LDL degradation was shifted away from the
liver so that approximately 70% of LDL-cholesterol uptake took place in the
extra-hepatic tissues of the WHHL rabbit. Thus, in the normal animal, the
primary function of receptor-dependent LDL transport is to promote the
rapid uptake and disposal of plasma LDL by the liver. In the absence of
such receptor activity, cholesterol balance across most individual organs
and the whole animal remains essentially normal and is mediated by the
receptor-independent process. Because of the much lower absolute clearance
rates manifested by this transport mechanism, however, substantial and
predictable elevations in the circulating plasma LDL-cholesterol levels are
required to maintain this balance.

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Copyright © 1987 by the American Society for Biochemistry and Molecular Biology.
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