Cholesterol-lowering properties of lupin peptides: molecular and functional investigations at Hepg2 cell line

Although statins are the main drugs for the treatment of hypercholesterolemic subjects, there is still interest for nutraceutics either to enhance the potency of drugs or to avoid their undesired side effects. An important dietary component able to reduce cholesterolemia is soy protein1, whose stimulated research on other legumes, in particular on lupin. Indeed investigations in suitable animal models2;3 and in the clinics4 demonstrated that this legume is able to lower cholesterol in case of moderate hypercholesterolemia. Having the objective of investigating the mechanism of this activity, in the present study we characterized the cholesterol lowering properties of lupin peptides, obtained after pepsin (P) and trypsin (T) hydrolysis. In particular, we performed a molecular and functional investigations of the effects on LDL receptor / SREBP2 pathway at HepG2 cell line. For the first time, we provided the experimental evidence that lupin peptides P and T are able to up-regulate the LDL receptor and SREBP2 proteins through an activation of PI3K/Akt/GSK3αβ pathways increasing the LDL-uptake at HepG2 cell line. References 1 Sirtori, C.R.; Eberini, I.; Arnoldi, A.; Hypocholesterolaemic effects of soya proteins: results of recent studies are predictable from the Anderson meta-analysis data. Brit. J. Nutr. 2007, 97, 816-822. 2 Sirtori, C.R.; Lovati, M.R.; Manzoni, C.; et al.; Proteins of white lupin seed, a naturally isoflavone-poor legume, reduce cholesterolemia in rats and increase LDL receptor activity in HepG2 cells. J Nutr, 2004, 134, 18-23. 3 Marchesi, M.; Parolini, C.; Diani, E.; et al.; Hypolipidaemic and anti-atherosclerotic effects of lupin proteins in a rabbit model. Brit. J. Nutr., 2008, 100, 707-710. 4 Sirtori, C.R.; Triolo, M.; Bosisio, R.; et al.; Hypocholesterolaemic effects of lupin protein and pea protein/fibre combinations in moderately hypercholesterolaemic individuals. Brit. J. Nutr., 2012, 107, 1176-1183.