ROLE OF HEPATIC LIPASE IN THE UPTAKE AND PROCESSING OF CHYLOMICRON REMNANTS IN RAT-LIVER

The participation of hepatic lipase in the initial uptake and processi ng of chylomicron remnants was studied in the isolated, perfused rat l iver. Hepatic lipase activity was either reduced by preperfusion of li vers with heparin or inhibited with specific rat hepatic lipase antibo dies. [H-3]palmitate-labeled chylomicron remnants were recirculated th rough control and treated livers for 15 min; the livers were then flus hed, homogenized, and endosome-rich fractions were isolated. Depletion of hepatic lipase activity by both methods reduced the uptake of chyl omicron remnants and hydrolysis of their component triglycerides by pe rfused rat livers, but at the same time significantly increased the ra te of endocytosis of those chylomicron remnants taken up. We conclude that hepatic lipase facilitates, but is not essential for, the initial uptake of chylomicron remnants by rat liver. Furthermore, endocytosis of chylomicron remnants does not require binding to hepatic lipase or the associated hydrolysis of remnant lipids.