Lipoprotein electrostatic properties regulate hepatic lipase association and activity

Abstract

The effect of lipoprotein electrostatic properties on the catalytic regulation of hepatic lipase (HL) was investigated. Enrichment of serum or very low density lipoprotein (VLDL) with oleic acid increased lipoprotein negative charge and stimulated lipid hydrolysis by HL. Similarly, enrichment of serum or isolated lipoproteins with the anionic phospholipids phosphatidylinositol (PI), phosphatidic acid, or phosphatidylserine also increased lipoprotein negative charge and stimulated hydrolysis by HL. Anionic lipids had a small effect on phospholipid hydrolysis, but significantly stimulated triacylglyceride (TG) hydrolysis. High density lipoprotein (HDL) charge appears to have a specific effect on lipolysis. Enrichment of HDL with PI significantly stimulated VLDL-TG hydrolysis by HL. To determine whether HDL charge affects the association of HL with HDL and VLDL, HL-lipoprotein interactions were probed immunochemically. Under normal circumstances, HL associates with HDL particles, and only small amounts bind to VLDL. PI enrichment of HDL blocked the binding of HL with HDL. These data indicate that increasing the negative charge of HDL stimulates VLDL-TG hydrolysis by reducing the association of HL with HDL. Therefore, HDL controls the hydrolysis of VLDL by affecting the interlipoprotein association of HL. Lipoprotein electrostatic properties regulate lipase association and are an important regulator of the binding and activity of lipolytic enzymes.

Small, Dense High-Density Lipoprotein-3 Particles Are Enriched in Negatively Charged Phospholipids

“…Modifications of the net surface charge of HDL by anionic molecules of PS, PI, and PA, all enriched in small HDL, can modulate chargedependent interactions with protein components, potentially improving HDL function. 11,52,53 Enhanced cholesterol efflux capacity observed by us in PS-enriched HDL is consistent with this hypothesis. Alternatively, HDL3 content of PS may serve as a biomarker of the presence of multiple proteins with diverse functions in this subpopulation.…”

Unraveling the complexities of the HDL lipidome

“…PI, PS, PG, and PA are negatively charged phospholipids that are present in lipoproteins in low amounts ( Table 1 ). These lipids may signifi cantly impact on the net surface charge of HDL ( 9,18,19 ), thereby modulating charge-dependent interactions with lipases, lipid transfer proteins, extracellular matrix, and other protein components. Major molecular species of these lipids in HDL remain to be reported.…”

Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis

“…A decreased PC/PE ratio is associated with liver damage, and normalization of PC/PE ratio has been reported to attenuate liver damage in a transgenic mouse strain with dietary steatohepatitis . Furthermore, activity of hepatic lipases or MTP may be limiting factors for the proper clearance of hepatic lipids (Sugimoto et al, 2002;Boucher et al, 2007). Inhibition of MTP activity was suggested to contribute,…”