YDFYPSSTKDQQS (P3), a peptide from lupin protein, absorbed by Caco-2 cells, modulates cholesterol metabolism in HepG2 cells via SREBP-1 activation

YDFYPSSTKDQQS (P3) is a peptide derived from the hydrolysis of lupin protein with pepsin that may be bioavailable, since it is absorbed in Caco-2 cells. In the framework of a research aimed at identifying new hypocholesterolemic peptides from plant proteins, this work provides evidence that P3 inhibits in vitro the functionality of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCoAR) and reports the characterization of the molecular mechanism through which this peptide modulates cholesterol metabolism in HepG2 cells. Specifically, through the inhibition of HMGCoAR activity, P3 improves the low density lipoprotein receptor protein levels via SREBP-1 activation, leading to a better ability of HepG2 cells to uptake extracellular low density lipoproteins with a final in vitro hypocholesterolemic effect. Practical applications: Plant proteins have many practical applications in human nutrition, since they are environmentally sustainable and provide useful health benefits mostly in the area of hypercholesterolemia prevention. The identification of novel bioavailable hypocholesterolemic peptides and the characterization of their mechanism of action may strengthen the awareness of the role of plant proteins in human health. The mechanism through which P3 exerts its hypocholesterolemic activity is distinctive in respect to other plant peptides. Hypocholesterolemic peptides from plant proteins may be included in dietary supplements.