Differential regulation of genes for intestinal cholesterol flux by epigallocatechin gallate (EGCG) and resveratrol (RES) in Caco‐2 cells: Potential role of histone deacetylases and sirtuins in intestinal cholesterol metabolism

Abstract

Despite well‐established cardio‐protective properties of phenolic compounds, their role in intestinal cholesterol metabolism is unclear. We investigated the effect of EGCG and RES on the transcriptional regulation of genes encoding intestinal cholesterol transporters and lipoprotein receptors in Caco‐2 cells. Cells treated with EGCG for 12 hr markedly increased ATP‐binding cassette transporter G5 (ABCG5) mRNA but decreased the expression of ABCA1, scavenger receptor class B type 1, Niemann‐Pick C1‐like 1 (NPC1L1), microsomal triglyceride transport protein and LDL receptor related protein 2 in a dose‐dependent manner (0–100 μM). In contrast, RES at 100 μM increased ABCA1 and NPClL1 mRNA. Of interest, EGCG significantly decreased the expression of all major histone deacetylase (HDAC), i.e., 1, 2, 3, 6, 7, 10, whereas RES had a minimal effect. Sirtuin (Sirt) 2–7 expression was also markedly repressed by EGCG but RES increased Sirt3, 4 and 5. The results indicate differential regulation of key transporters involved in intestinal cholesterol efflux by EGCG and RES. The over‐arching objective of this research will be to relate changes in the gene expression profile to the promotion of cholesterol flux from the basolateral to apical side of enterocytes. Importantly, this study suggests that expression of the aforementioned intestinal transporters may be linked the regulation of HDAC and Sirt in the intestine.Grant Funding Source: Supported by USDA Hatch fund