Enrichment of apolipoprotein B-48 in the LDL density class following in vivo inhibition of hepatic lipase.
In order to explore the in vivo function of hepatic lipase, rats were injected with goat anti-rat hepatic lipase serum which produced a complete and specific inhibition of heparin-releasable hepatic lipase. In the fasting rats, protein, phospholipid and free cholesterol expressed as either mass or percent weight increased significantly in low-density lipoprotein (LDL) and high-density lipoprotein 2 (HDL-2) fractions. These three constituents were not affected in the VLDL and HDL-3 lipoproteins. In the fat-loaded (1 ml corn oil) rat, 6 h post inhibition of hepatic lipase triacylglycerol, phospholipid and free cholesterol concentrations in the d less than 1.006 fraction were 2.5-fold higher in the inhibited animals than in the control rats. The composition of the d less than 1.006 fraction was also affected. Expressed as percent mass, protein was lower (5.2 +/- 1.2 vs. 10.3 +/- 1.5, P less than 0.001) as was cholesteryl ester (1.7 +/- 0.7 vs. 2.6 +/- 0.4, P less than 0.01); triacylglycerol was elevated (77.2 +/- 4.0 vs. 72.6 +/- 2.4, P less than 0.025), as was free cholesterol (3.0 +/- 0.6 vs. 2.4 +/- 0.2, P less than 0.025). Overall, inhibition lowered the ratio of surface-to-core constituents suggesting a larger mean particle diameter. SDS-polyacrylamide gel electrophoresis showed the intermediate- and low-density lipoprotein from treated rats to be significantly enriched in apolipoprotein B-48. In the LDL fraction, apolipoprotein B-48 accounted for 62 +/- 14% of the total apolipoprotein B in the inhibited rats, vs. 12 +/- 2% in the control rats. The above results support the previously described in vivo function of hepatic lipase as a phospholipase. In addition, the results demonstrate a role of hepatic lipase in the catabolism of chylomicrons. Since removal of apolipoprotein B-48-containing lipoproteins is dependent upon apolipoprotein E, their appearance in the LDL fraction implies a masking of apolipoprotein E-binding determinants.
D000818:Animals; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D003429:Cross Reactions; D004591:Electrophoresis, Polyacrylamide Gel; D006041:Goats; D007120:Immunochemistry; D008049:Lipase / Q000037:antagonists & inhibitors*; D008074:Lipoproteins / Q000097:blood; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL / Q000097:blood*; D008099:Liver / Q000201:enzymology*; D008297:Male; D010743:Phospholipids / Q000097:blood; D051381:Rats
D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL; D010743:Phospholipids; D002784:Cholesterol; D008049:Lipase