Gastric lipase and PLRP2 trigger the activity of pancreatic lipase on various emulsions stabilized by phospholipids or galactolipids.

Dietary lipids are often consumed as oil-in-water emulsions, in which the interfacial structure governs enzyme accessibility and lipid digestion. This study investigated how the prior action of gastric lipase (GL) or pancreatic lipase-related protein 2 (PLRP2) modulates the subsequent activity of pancreatic lipase (PL) and triacylglycerol (TAG) hydrolysis. O/W emulsions of linseed oil stabilized with phosphatidylcholine (PC) or galactolipids (digalactosyldiacylglycerol, DGDG) were compared with Intralipid® and fresh bovine milk as reference substrates. Real time continuous assay of free fatty acid (FFA) release by the pHstat technique allowed determining kinetic parameters (initial and maximum (Vmax) lipolysis rates; lag time, τ) of emulsion lipolysis by pancreatic lipase (PL; either from porcine pancreatic extracts or purified human pancreatic lipase and colipase), following preincubation with either recombinant dog gastric lipase (rDGL, pH 5.0) or guinea pig PLRP2 (GPLRP2, pH 8.0). Regardless of the type of emulsion, PL, showed a weak activity only revealed after long τ. Preincubation with rDGL or GPLRP2 markedly enhanced lipolysis by PL and reduced or suppressed lag times for reaching Vmax. These findings show that the PL activity is not intrinsically limited by polar lipids at the interface, but dynamically regulated by prior interfacial conditioning. A mechanistic basis for the synergistic and sequential action of lipases is proposed, involving either a direct action of GL on TAG through its penetration of the interfacial layer or the digestion of DGDG or PC by PLRP2, both resulting in the production of FFAs facilitating PL-colipase adsorption. Early lipolysis events thus emerge as key determinants of lipid digestion.