Plasma clearance and liver uptake of chylomicron remnants generated by hepatic lipase lipolysis, evidence for a lactoferrin-sensitive and apolipoprotein E-independent pathway

Chylomicrons labeled with [H-3]cholesterol and [C-14]triglyceride fatty aci ds were lipolyzed by hepatic lipase (HL) in vitro and then injected intrave nously into normal mice fed low or high-fat diets, and into apolipoprotein (apo) E-deficient mice, In normal mice fed the high-fat diet and injected w ith non-lipolyzed chylomicrons, the plasma clearance and hepatic uptake of the resulting [H-3]cholesterol-labeled remnants was markedly inhibited. In contrast, chylomicrons lipolyzed by HL were taken up equally rapidly by the livers of mice fed the low- and high-fat diets. The removal of non-lipolyz ed chylomicrons lacking apoE from the plasma of apoE-deficient mice was inh ibited, but not the removal of chylomicrons lipolyzed by HL, Pre-injection of lactoferrin into normal mice inhibited the plasma clearance of both non- lipolyzed chylomicrons and chylomicrons lipolyzed by HL, The removal of HL from the surface of the lipolyzed particles by proteolytic digestion did no t affect their rapid uptake, indicating that the hepatic recognition of the lipoproteins was not mediated by HL. These observations support previous f inding that phospholipolysis of chylomicrons by hepatic lipase generates re mnant particles that are rapidly cleared from circulation by the liver. The y also support the concept that chylomicron remnants can be taken up by the liver by an apolipoprotein E-independent mechanism, We hypothesize that th is mechanism is modulated by the remnant phospholipids and that it may invo lve their interaction with a phospholipid-binding receptor on the surface o f hepatocytes such as the class B scavenger receptor BI.