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

Abstract

A a S T R A C T 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 3H or 14C. 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

Regulation of the plasma non-esterified fatty acid concentration in the postprandial state

“…However, whilst LPL is usually considered as an enzyme regulating fat storage, it may also play an important role in the delivery of NEFA into the circulation. It has long been recognized from animal experiments that about 50 % of LPL-derived fatty acids are released directly into the plasma, as opposed to entrapment and esterification in tissues at the site of action (Bergman et al 1971;Scow, 1977). This value is borne out in human studies of the tissue- specific release of fatty acids during the postprandial period (Frayn et al 1994, 19956).…”

Increased Dietary Substrate Delivery Alters Hepatic Fatty Acid Recycling in Healthy Men

“…A final potential source of fatty acids flowing to the liver postprandially comes from dietary fatty acid influx, which is mediated by chylomicrons produced by the intestine. Animal studies demonstrated that dietary fatty acids were cleared to the liver in vivo (11,12) and that chronic consumption of higher-fat diets results in elevations in liver fat (13,14). However, this pathway has not been measured directly in humans and may provide a significant route of fatty acids used for hepatic TAG synthesis (15).…”

Hepatic Sinusoidal Endothelium in Goats

“…If this were the case, then the hypothesis of Fraser et al, (1978) Ihat the endothelial fenestrae of the rat liver are the first stage of recognition of chylomicron remnants and of the rejection of their larger, parent chylomicrons could not apply to the ruminants. The work of Bergman et al, (1971) suggests that the processes of chyloinicron remnant removal in sheep does not differ greatly from that in nonruminants, and recent work in this laboratory has shown that the basement membrane observed in the sheep sinusoid is artefactual (Wright ei al, 1983). The findings reported here indicate that the same is true in the goat.…”