Abstract
The uptake and metabolism of lymphatic large chylomicrons from fat-fed rats, lymphatic small chylomicrons from glucose-fed rats, and hepatic very low density lipoproteins from perfusates of isolated livers, and of remnants produced from these lipoproteins in functionally eviscerated rats were studied in the isolated perfused rat liver. All lipoproteins were labeled isotopically in their cholesteryl ester and triglyceride moieties. Uptake of the labeled lipids or large chylomicrons was slow and limited, but these lipids in small chylomicrons and hepatic very low density lipoproteins were taken up and metabolized progressively and at equal rates. Incubation with very low density lipoprotein-free plasma increased the content of C apolipoproteins in small chylomicrons and hepatic very low density lipoproteins and greatly retarded the hepatic uptake of their labeled lipids. In remnants from all sources, which are depleted of C apolipoproteins but not of apolipoprotein E, the labeled lipids were rapidly taken up and metabolized. Neither extensive hydrolysis of core triglycerides nor the production of monoglycerides was required for this rapid hepatic uptake. These results are consistent with the hypothesis that one or more of the C apolipoproteins opposes and apolipoprotein E promotes recognition of triglyceride-rich lipoproteins by a hepatic receptor.
Highlights
Crons fromglucose-fedrats, and hepatic verylow den- Chylomicrons are taken up by the liver only to a limited sity lipoproteins from perfusates ofisolated livers, and extent (5-IO), but the core lipids of chylomicron remnants are of remnants producedfrom these lipoproteins in func- rapidly taken up and catabolized by the liver in several tionally eviscerated rats were studied in the isolated, mammalian species (2,ll-13)
As remnant partially degraded particles called remnants ( 2, 3 ) .As lipopro- formation is accompanied by depletion of C apoproteins, it tein lipase depletes the lipoprotein core of triglycerides, some appears that the proportions of the protein components on of the surface phospholipids, together with most of the C the surface of TG-rich lipoproteins may be crucial to recogapoproteins and, in the case of chylomicrons, apoproteins A- nition of these particles by a hepatic receptor
In experiments lasting longer than 30 min, 0.25 ml of 10%glucose in 0.15M NaCl was injected into atail vein every 20 min. In these preparationsthe liver proved to be entirely excluded from the circulation as no more than 0.5%of injected isotope was recovered in the liver and the attached part of the lower vena cava 60 min after injection of lymphatic chylomicrons or hepatic VLDL labeled with [3H]cholesterol or acetylated human "51-labeledlow density lipoprotein, which is known to be readily taken up by the liver [23]
Summary
Animals-Male Sprague-Dawley rats, weighing 300 to 350 g, maintained on standard Purina rat chow In experiments lasting longer than 30 min, 0.25 ml of 10%glucose in 0.15M NaCl was injected into atail vein every 20 min In these preparationsthe liver proved to be entirely excluded from the circulation as no more than 0.5%of injected isotope was recovered in the liver and the attached part of the lower vena cava 60 min after injection of lymphatic chylomicrons or hepatic VLDL labeled with [3H]cholesterol or acetylated human "51-labeledlow density lipoprotein, which is known to be readily taken up by the liver [23]. After 45 to 60 min, the liver was flushed with 60 ml of perfusate in a single pass; 60 mlof fresh medium was recirculated for 2 h This procedure was found to be necessary because up to6% of the [3H]palmitate-labeled hepatic VLDL accumulated as free fatty acids during perfusion with the first medium. Results are given as the mean of n experiments _t S.D
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