Chylomicron metabolism in rats: kinetic modeling indicates that the particles remain at endothelial sites for minutes.
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.
Departments of Surgical and Perioperative Sciences, Anaesthesiology and Intensive Care, Umeå University, S-901 87 Umeå, Sweden.
Magnus
M
Hultin
Roger
R
Savonen
Olivier
O
Chevreuil
Thomas
T
Olivecrona
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002914:Chylomicrons / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D004730:Endothelium, Vascular / Q000378:metabolism*; D004822:Epididymis / Q000378:metabolism; D008066:Lipolysis; D008099:Liver / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009829:Oleic Acids / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014801:Vitamin A / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*
D002914:Chylomicrons; D009829:Oleic Acids; D014801:Vitamin A
adipose tissue; chylomicron remnants; chylomicrons; compartmental modeling; endothelium; heart; lipolysis and fatty acid metabolism; lipoprotein kinetics; lipoprotein lipase; margination