Abstract
Chylomicrons labeled in vivo with (14)C-oleic acid (primarily in triglycerides, providing a tracer for lipolysis) and (3)H-retinol (primarily in ester form, providing a tracer for the core lipids) were injected into rats. Radioactivity in tissues was followed at a series of times up to 40 min and the data were analyzed by compartmental modeling. For heart-like tissues it was necessary to allow the chylomicrons to enter into a compartment where lipolysis is rapid and then transfer to a second compartment where lipolysis is slower. The particles remained in these compartments for minutes and when they returned to blood they had reduced affinity for binding in the tissue. In contrast, the data for liver could readily be fitted with a single compartment for native and lipolyzed chylomicrons in blood, and there was no need for a pathway back to blood. A composite model was built from the individual tissue models. This whole-body model could simultaneously fit all data for both fed and fasted rats and allowed estimation of fluxes and residence times in the four compartments; native and lipolyzed chylomicrons ("remnants") in blood, and particles in the tissue compartments where lipolysis is rapid and slow, respectively.
Highlights
Chylomicrons labeled in vivo with 14C-oleic acid and 3H-retinol were injected into rats
The results indicated that a large fraction of chylomicron TGs leaves plasma with the particles, and that most of the fatty acids from chylomicron TGs mix into the same metabolic compartment as do plasma FFAs
The major questions asked were: What is the nature of the interaction of chylomicron particles with the vascular endothelium? Are the interactions short-lived so that there is in effect near-equilibrium between particles in blood and at the endothelium or is the interaction of a chylomicron particle with an endothelial binding-lipolysis site more long-lived? If so, can we estimate the residence time?
Summary
Chylomicrons labeled in vivo with 14C-oleic acid (primarily in triglycerides, providing a tracer for lipolysis) and 3H-retinol (primarily in ester form, providing a tracer for the core lipids) were injected into rats. In the epididymal fat pad of fed rats, chylomicron core label rose to about 0.8% of the injected dose per gram tissue at 13 min and decreased slowly. Our present data for radioactivity in TGs and FFAs in blood can be fitted to this model with adjustment of some rate constants (supplementary Fig. I).
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