Current Status and Prospects of Research on Cholesterol Metabolism-improving Peptides Derived from Food Proteins

Abstract

Our group has identified lactostatin (IIAEK) as the first documented hypocholesterolemic pentapeptide derived from bovine milk β-lactoglobulin that exerts an effect in rats. Lactostatin activates expression of the gene for cholesterol 7α-hydroxylase (CYP7A1), which is the rate-limiting enzyme for cholesterol degradation via a newly characterized regulatory pathway for calcium channel-related MAPK signaling in HepG2 cells. The novel soy protein hydrolysate with bound phospholipids exhibits an excellent hypocholesterolemic action in hypercholesterolemic patients. Soystatin (VAWWMY), derived from soybean glycinin, is the first peptide identified to inhibit intestinal cholesterol absorption in rats. The hypocholesterolemic activity of soystatin could be enhanced by peptide array. We have also discovered a novel cholesterol metabolism-improving dipeptide FP derived from bovine heart protein. FP acts as a ligand for the peroxisome proliferator-activated receptor and acts by improving cholesterol metabolism through PepT1. A novel cholesterol metabolism-improving tripeptide, RPR, derived from protamine exhibited effects against obesity and non-alcoholic fatty liver. In order to further develop cholesterol metabolism-improving peptide research, human trials, clarification of the molecular-level mechanism of action (including target molecule identification) and commercialization will be necessary.