IAVPGEVA, IAVPTGVA, and LPYP, three peptides from soy glycinin, modulate cholesterol metabolism in HepG2 cells through the activation of the LDLR-SREBP2 pathway

Although the hypocholesterolemic activity of soy foods is well known from decades, its molecular mechanism is still poorly understood. The aim of this study was a detailed molecular characterization of the activity of IAVPGEVA, IAVPTGVA, and LPYP, three peptides from soy glycinin hydrolysis, which in the past had been shown to be competitive inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCoAR). HepG2 cells were treated with these peptides and the samples were analyzed with a combination of molecular techniques. The experiments demonstrated that they are able to interfere with the catalytic activity of HMGCoAR and to modulate the cholesterol metabolism, through the activation of the LDLR-SREBP2 pathway, increasing the ability of HepG2 cells to uptake the LDL. This involves also the activation of AMPK and ERK 1/2. For the first time, this study provides a characterization of the molecular mechanism.