Purification of Rat Hepatic Lipase Essentially Free of Apolipoprotein E and Apolipoprotein B

Hepatic lipase (HL) is necessary for efficient clearance of triglyceride-rich lipoproteins from plasma (1 ). In humans, HL deficiency leads to the accumulation of triglyceride-rich intermediate density lipoproteins (IDL), LDL, and large HDL (2 –4 ). Inhibition of hepatic lipase in rats with specific antibodies to HL (5 –12 ) causes similar changes in plasma lipoprotein patterns, with accumulation of IDL and chylomicron remnants in the low density ranges and increases in the large HDL subfractions. In isolated, perfused rat livers inhibition of hepatic lipase with antibodies or removal of HL by heparin perfusion reduces the uptake of chylomicron remnants (13 ). Finally, recent studies with cultured hepatoma cells over-expressing human HL (14 ) demonstrate a threefold increase in binding and uptake of β-VLDL and chylomicron remnants when compared to non-transfected cells. Hence, several studies have shown that decreased HL activity inhibits clearance of triglyceride-rich lipoproteins, while overexpression of HL facilitates clearance of these particles.