Identification and molecular mechanism study of novel pancreatic lipase and cholesteryl esterase inhibitory peptides from yak whey protein hydrolysates.

This study aims to prepare, purify, and identify novel pancreatic lipase (PL) and cholesterol esterase (CE) inhibitory peptides from yak whey protein (YWHP), and to elucidate their underlying mechanisms of action. Results showed that bromelain effectively hydrolyzed YWHP into smaller peptide fragments. Ultrafiltration of yak whey protein hydrolysates (YWPHs) produced three fractions (>10 kDa, 3-10 kDa, and < 3 kDa). The <3 kDa fraction displayed PL and CE inhibitory activities of 36.34 ± 1.00% and 35.85 ± 0.65%, respectively. Fraction II obtained from Sephadex G-25 exhibited strong inhibition on PL and CE. LC-MS identified three novel PL and CE inhibitory peptides (FDI, ADIF, and FDL).These peptides inhibited lipase activities mainly by occupying the catalytic sites and substrate-binding pockets of PL and CE. All three peptides synthesized via solid-phase peptide synthesis exhibited inhibitory activities against both PL and CE. This study provides a theoretical basis for developing hypolipidemic functional products.