Enrichment of soy protein-derived peptides that decrease pancreatic lipase activity using heat-treated porous silica gel and their relationship with bile acid binding activity.

Excessive lipid absorption is a key factor in obesity. Lipids are solubilized in the gut via bile acid (BA) micelles, where pancreatic lipase hydrolyzes them for absorption. This study aimed to enrich pancreatic lipase inhibitory (PLI) peptides from food protein hydrolysates and clarify their inhibition mechanisms. We used heat-treated porous silica gel (HTSG) to selectively enrich basic and hydrophobic peptides through adsorption-desorption. While HTSG has previously enriched PLI peptides, the mechanism remained unclear. Since basic and hydrophobic peptides can bind strongly to BAs like taurocholic acid, we explored their BA-binding and PLI activities. Pepsin hydrolysates from casein, soybean, pea, and rice endosperm were tested with 1 mM sodium taurocholate (TCA). TCA increased lipase activity over 2.5-fold. Soybean pepsin hydrolysate (SPH) showed notable PLI activity, further enhanced approxiamtely 3-fold after HTSG treatment (SPH (after)). LC-MS/MS of SPH (after) identified 1461 peptides. Among 38 high-abundance peptides (Z ≥ 2) chemically synthesized, 9 inhibited pancreatic lipase in the presence of TCA. BA-binding activity was assessed via micelle disruption. Seven of the nine peptides disrupted over 50 % of micelles. Docking simulation was conducted and peptides that exhibited PLI activity even without TCA and showed TCA-binding activity were predicted to bind directly to pancreatic lipase. In summary, we identified 9 PLI peptides from SPH, most of which inhibit pancreatic lipase by binding to BAs. HTSG-based enrichment offers a promising strategy to obtain bioactive peptides that may serve as functional ingredients for obesity prevention.