Differential Regulation of Liver Gene Expression by in vitro Digested Soy and Caseinate

The mechanisms underlying the cholesterol lowering effects of soy protein remain unknown. The current study investigated the gene expression profile of a human liver cell line, HepG2, after 18 hours of exposure to 1 mg/ml soy (S) or caseinate (C) protein. S or C was predigested with pepsin and pancreatin to mimic gastrointestinal digestion. Lovastatin (L) (10 μM) and baseline control (Con) were included. Whole genome expression was profiled using an Illumina® microarray. Results indicated that 268 genes were regulated by either S and/or C versus Con, with the patterns of regulation observed being unique to the protein hydrolysate studied. Real‐time quantitative PCR (RT‐qPCR) experiments were conducted using a subset of genes differentially expressed by microarray with a focus on genes that regulate lipid metabolism. RT‐qPCR confirmed the microarray expression profiles observed for L and showed similar trends for S and C compared to Con. RT‐qPCR results showed that the MYLIP gene, whose protein product is responsible for LDL‐R degradation, decreased in HepG2 cells after S treatment compared to Con (0.45 ± 0.076 fold, p = 0.002) or C (0.55 ± 0.092, p = 0.018), with no significant difference between C and Con. Therefore, the cholesterol lowering effect of soy protein may partially be due to increased liver cholesterol uptake as a result of decreased LDL‐R degradation. Funded by Solae, LLC