Journal of Lipid Research, Vol 28, 351-360, Copyright © 1987 by Lipid Research, Inc.
Secretion and uptake of nascent hepatic very low density lipoprotein by perfused livers from fed and fasted rats
HG Wilcox and M Heimberg
Livers from fed or 24-hr fasted male rats were perfused in a recycling
system. VLDL labeled with [1-14C]oleate (95% in triglyceride), produced in
separate perfusions of livers from fed rats, was added to the medium as a
pulse. Uptake of VLDL 14C-labeled triglyceride by livers from fasted rats
was less than that from fed rats regardless of addition of oleate. During
the interval in which radioactive triglyceride was taken up, the mass of
triglyceride in the medium increased, indicative of the synthesis and net
secretion of triglycerides. The rates of secretion of VLDL and uptake of
VLDL were both more rapid in livers from fed rats in comparison to those
from fasted animals. It was calculated that about 50% of the triglyceride
synthesized and secreted by the liver was taken back by livers from fed
rats. The VLDL from livers of fasted rats did not contain any apoE
detectable by SDS gel electrophoresis or by radioimmunoassay when no fatty
acid or 166 mumol of oleic acid was infused. In contrast, apoE comprised 6%
of the VLDL apoprotein derived from perfusion of livers from fed animals in
the absence of added fatty acid, and 20% when the fed livers were infused
with 166 mumol of oleic acid. However, the net output (accumulation) of
apoE by fasted liver was only two-thirds that from fed livers. When
lipoprotein-free rat plasma containing apoE (4 mg/dl) was used in place of
bovine serum albumin, the VLDL secreted by livers from either fed or fasted
rats contained apoE and was taken up to a similar extent by such livers.
These data suggested that the apoE of the d greater than 1.21 g/ml fraction
was transferred to newly secreted VLDL which then stimulated uptake of the
VLDL by livers from fasted rats. With further stimulation of secretion of
VLDL triglyceride by infusion of 332 mumol of oleic acid/hr, the percent of
apoE in the VLDL secreted by livers from fasted rats increased to 20%,
which was similar to that of the VLDL produced by livers from fed rats when
either 166 or 332 mumol/hr was infused. These data suggest a relationship
between rates of hepatic secretion of VLDL (TG) and apoE, and the
association of apoE with the secreted VLDL. During fasting, reduced
secretion of both VLDL and apoE resulted in a VLDL particle that was
considerably diminished in content of apoE and, therefore, that would be
taken up by the liver at a reduced rate, in comparison to that observed in
the fed animal.