Determinants of hepatic uptake of triglyceride-rich lipoproteins and their remnants in the rat.

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.