Lupin peptides lower LDL cholesterol through an up-regulation of LDL receptor / SREBP2 pathway at HepG2 cell line

Lupin is a protein-rich grain legume, which has been domesticated long time ago and cultivated in different continents, either for animal or human nutrition. The seeds of these plants have some favorable features, in particular, the protein percentage is comparable to that of soybean 1 and the content of indispensable amino acids is only slightly inferior. Besides these important nutritional features, lupin seed may also provide some health benefits, particularly in the area of dislipidemia prevention. Previous experiments in suitable animal models and in mild hypercholesterolemic individuals have shown that the consumption of lupin proteins may be useful for controlling total and low-density-lipoprotein (LDL) cholesterol levels2, 3,4. With the objective of providing evidences that peptides generated by the digestion of lupin proteins may be responsible of the observed activities and for investigating the mechanism of action, HepG2 cells were treated with lupin peptides obtained either by pepsin (P) or trypsin (T) hydrolysis and molecular and functional investigations were performed on the LDL receptor / SREBP2 pathway (Figure 1). For the first time, this report provides the experimental evidence that peptides obtained from the hydrolysis of lupin proteins are able to interfere with the HMGCoAR activity, up-regulating the LDL receptor and SREBP2 proteins via the activation of PI3K/Akt/GSK3β pathways and increasing the LDL-uptake at HepG2 cell line.