Quantitative studies of the metabolism of chylomicron triglycerides and cholesterol by liver and extrahepatic tissues of sheep and dogs.

Unanesthetized sheep and dogs, previously fitted with indwelling catheters in the aorta, lower vena cava, mesenteric, portal, left hepatic and jugular veins, were given constant intravenous infusions of lymph in which the chylomicron lipids were variously labeled with (3)H or (14)C. Para-aminohippuric acid was infused into the mesenteric venous catheter for measurement of portal and hepatic venous blood flow. In some animals, alternately labeled free fatty acids bound to albumin were mixed with the lymph to be infused. In both species, chylomicron triglyceride fatty acids were taken up in the region drained by the lower vena cava and portal vein and free fatty acids derived from hydrolysis of these triglycerides were extensively recycled in the blood. Direct uptake of triglyceride fatty acids also occurred in liver and accounted for about 10% of the total triglyceride fatty acids removed from the blood in sheep and 22% in dogs. In sheep, 10% and, in dogs, about 40% of these triglyceride-fatty acids were released into the blood as free fatty acids. The free fatty acids recycled from various regions accounted for a substantial fraction of the chylomicron fat eventually deposited in each tissue. Uptake of chylomicron cholesterol from the blood of sheep occurred primarily in liver and to a small extent in certain tissues drained by the portal vein. The results obtained, together with other available data, demonstrate that chylomicron triglycerides are removed primarily in extrahepatic tissues of both species, while the liver removes cholesterol contained in chylomicron "skeletons" from which most of the triglycerides have been removed. The quantitative differences between transport of chylomicron lipid in sheep and dogs may be related to known differences in the structure of their hepatic sinusoids.