METABOLISM OF LIPOPROTEINS CONTAINING APOLIPOPROTEIN-B IN HEPATIC LIPASE-DEFICIENT MICE

Mice lacking hepatic lipase have been reported to express mild hyperli pidemia characterized by increased concentrations of large high densit y lipoproteins, but normal concentrations of lipoproteins containing a polipoprotein B, Whereas hepatic lipase has been implicated in the cle arance and processing of chylomicron remnants in rats, no such defect was found in these mice, We have further characterized the abnormal li poprotein phenotype in young hepatic lipase-deficient mice and have fo und more pronounced elevations of high density lipoproteins associated in particular with a 5-fold increase in plasma concentrations of apol ipoprotein E, In addition, there was a reduction ire the concentration of low density lipoproteins containing apolipoprotein B-100 and B-48 relative to precursor lipoproteins of lower density and a pronounced d eficiency of apolipoprotein B-containing low density lipoproteins with density exceeding 1.029 g/mL, Conversion of radiolabeled rabbit inter mediate density Lipoproteins to low density lipoproteins was reduced b y 6-fold as compared with wild-type mice. Although clearance of choles teryl ester-labeled chylomicrons from the blood was unimpaired in the deficient mice, that of chylomicron remnants was reduced, Furthermore, endocytosis of chylomicron cholesteryl esters into liver cells occurr ed more rapidly than in wild-type mice, The unimpaired hepatic clearan ce of injected chylomicron particles in hepatic lipase-deficient mice may be the result of greater acquisition of apoE from high density lip oproteins during remnant formation. These studies thus demonstrate a c ritical role for mouse hepatic lipase in the formation of small, dense low density lipoproteins, as well as participation in the normal clea rance and processing of chylomicron remnants.