Oak Tannin and Unoaked and Oaked Wine Extracts Influence Gene Expression in HepaRG Human Liver Cells

Abstract

Previous work from our laboratory has shown that both a purified toasted oak powder and extracts made from unoaked and oaked red wines influenced physiological parameters, metabolism and hepatic gene expression in high-fat fed C57/BL6J male mice (Luo et al., 2020).  Impacted pathways included glucose metabolism, liver fat accumulation, markers of chronic inflammation, and expression of the Gsta1 mRNA.  

In the present study, we utilized a novel cell model in a cell culture system, the HepaRG cell line.  These cells more closely resemble isolated human hepatocytes, and in particular, express robust levels of nuclear hormone receptors which may be involved in the sensing of phytochemicals.  We directly exposed HepaRG cells to three mixtures, the toasted oak tannin powder (OT), and two de-alcoholized extracts made from identical red wines fermented and aged in either steel tanks or oak barrels (oaked and unoaked wine concentrates; OWC & UWC).  In addition, other groups of cells were exposed to purified, individual compounds that may either be present in oaked wines or biotransformed by enterocytes of the small intestine:  ellagic acid (EA) and urolithin B (UroB).  OT concentration was 10 mg/L and OWC and UWC was 0.2 mL/L.  EA concentration was 300ug/L and UroB was 200ug/L.  Cells were exposed for a period of 48 hours, after which total RNA was isolated and used to perform ClariomB microarray gene expression analysis.  Data from these analyses is shown as both lists of most up- and down-regulated genes vs. untreated controls; with Venn diagrams to show commonality between different treatments, and upset plot analyses.