We showed previously that net secretory output of
apolipoprotein B (
apo B) from cultured human
hepatoma cells (HepG2) is regulated by rapid reuptake of nascent
lipoproteins before they have diffused away from the vicinity of the cells. We now sought to determine if the nascent
lipoproteins could be remodeled to enhance or impede reuptake. We found that
lipoprotein lipase (LpL), an
enzyme that hydrolyzes
lipoprotein triglyceride, reduced HepG2 output of
apo B to one-quarter to one-half of control. The reduction was apparent during co-incubations as short
as 2 h and as long as 24 h.
Heparin, which blocks receptor-mediated binding of
lipoproteins, abolished the effect of LpL on
apo B output, without causing
enzyme inhibition. To assess uptake directly, we prepared labeled nascent
lipoproteins. LpL tripled the cellular uptake of labeled nascent
lipoproteins, from 15.2% +/- 0.7% to 48.7% +/- 0.3% of the total applied to the cells. Cellular uptake of 125I-labeled anti-
LDL receptor IgG was unaffected by LpL; thus, LpL enhanced reuptake by altering
lipoproteins, not receptors. Because LpL is present in the space of Disse in the liver, we conclude that LpL may act on newly secreted
lipoproteins to enhance reuptake in vivo. LpL deficiency would reduce local reuptake of
apo B, which would appear as overproduction, thereby providing a mechanistic link between partial LpL deficiency and
familial combined hyperlipidemia.