Lipoprotein lipase enhances removal of chylomicrons and chylomicron remnants by the perfused rat liver.

• Lipoprotein lipase has been found to efficiently mediate binding of lipoproteins to cell surfaces and to the low density lipoprotein (LDL) receptor-related protein (LRP) under cell culture conditions (Beisiegel et al. 1991. Proc. Natl. Acad. Sci. USA. 88: 8242-8346). This supports the previously proposed idea that the lipase could have a role in receptor-mediated uptake of chylomicron remnants in the liver. We have investigated the effects of lipoprotein lipase on the clearance of chylomicrons during perfusions of rat livers. The chylomicrons were doubly labeled in vivo with [14C]retinol (in retinyl esters) and with [3H]oleic acid (in triacylglycerols) and were collected from lymph. In the absence of any lipase the clearance of chylomicron label from the perfusion medium was slow. Addition of lipoprotein lipase caused lipolysis of chylomicron triacylglycerols as evidenced by increased levels of 14C-labeled fatty acids in the perfusate. Simultaneously, the level of [14C]retinyl esters in the perfusate decreased dramatically, indicating core-particle removal. Similar effects were seen with an unrelated lipase from Pseudomonas fluorescens. To discriminate between the effects of lipolysis and a true liganding effect of the lipoprotein lipase protein, the active site inhibitors tetrahydrolipstatinR and hexadecylsulfonylfluoride were used to reduce or totally inhibit the catalytical activity. With lipase covalently inhibited by the latter inhibitor, lipolysis during perfusions was low or absent. Nonetheless, the inhibited enzyme had a clear effect on the removal of chylomicrons by the liver. With 1.2 micrograms of inhibited lipase/ml perfusate, about 70% of the core label had been removed after 15 min as compared to about 20% in perfusions without lipase. With identical amounts of active lipoprotein lipase protein, more than 90% of the label was removed. We conclude that any lipase causing lipolysis of chylomicrons can stimulate their clearance by the liver, but that lipoprotein lipase has an additional effect on the removal, which is not dependent on its catalytic activity.

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MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)

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