Apolipoprotein A-I regulates lipid hydrolysis by hepatic lipase

Association of hepatic Lipase (HL) with pure heparan sulfate proteoglycans (HSPG) has little effect on hydrolysis of high density lipoprotein (HDL) pa rticles, but significantly inhibits (>80%) the hydrolysis of low (LDL) and very low density lipoproteins (VLDL). Lipolytic inhibition is associated wi th a differential ability of the lipoproteins to remove HL from the HSPG. L DL and VLDL are unable to displace HL, whereas HDL readily displaces HL fro m the HSPG, These data show that HSPG-bound HL is inactive. Purified apolip oprotein (apo) A-I is more efficient than HDL at liberating HL from HSPG, a nd HL displacement is associated with the direct binding of apoA-I to HSPG. However, displacement of HL by apoA-I does not enhance hydrolysis of VLDL particles. This appears due to the direct inhibition of HL by apoA-I, Both apoA-I and HDL are able to inhibit VLDL lipid hydrolysis by up to 60%. Inhi bition of VLDL hydrolysis is associated with the binding of apoA-I to the s urface of the VLDL particle and a concomitant decreased affinity for HL. Th ese data show that apoA-I can regulate lipid hydrolysis by HL by liberating ! activating the enzyme from cell surface proteoglycans and by directly mod ulating lipoprotein binding and hydrolysis.