TABLE 1.
Food ligands of nuclear receptors and influence on epigenetic regulation1
| Food compound | Metabolic/epigenetic effects |
| ER | |
| Genistein, daidzein, equol | Potent activators of ERβ and ERα promoters through regulation of DNMT expression and enhanced HAT activity (122) |
| Resveratrol | Increases ER promoter methylation and inhibits HDAC (150) |
| EGCG | Induces chromatin remodeling by altering histone acetylation and methylation status leading to ER reactivation (47) |
| I3C | Disrupts interaction between ERα and Sp1 on promoter of the hTERT gene (151) |
| AR | |
| EGCG | Lowers AR acetylation and activation by inhibiting HAT activity (152) |
| DIM | Reverses epigenetic silencing of miR-34a in prostate cancer, inducing inactivation of the AR (153) |
| AhR | |
| Resveratrol | Prevents BRCA-1 promoter hypermethylation and silencing (49, 126) |
| EGCG | Inhibits binding of AhR to XRE in endothelial cells (154); directly inhibits DNMT by binding to catalytic subunit (122) |
| DIM, I3C | Abrogate dioxin-induced recruitment of AhR and AcH4 to the COX-2 promoter (35) |
| Quercetin, kaempferol, genistein, daidzein, apigenin | Inhibit AhR binding to XRE of target genes, such as CYP1A1 (123) |
| PPARα/γ | |
| Resveratrol | Activates PPARs in vitro and in vivo leading to reduced COX-2 expression (155) |
| PPARα | |
| Eicosanoids | Regulate β-oxidation genes in liver; inhibit NF-κB transcription in heart (156) |
| PPARγ | |
| Arachidonic acid | Increases adipocyte differentiation in brown adipose tissue (156) |
| Genistein | Promotes adipogenesis at concentrations >1 μmol/L through mechanisms involving downregulation of ER-mediated transcription (156) |
| Daidzein and equol | Activate PPARγ at lower concentrations than genistein (157) |
| CLA | Inhibits adipogenesis and inflammation, promotes osteoblastogenesis (158) |
| PPARβ/δ | |
| PUFAs | Increase FA oxidation (156) |
| PGs | Lower TGs and free FA amounts in adipose tissue (156) |
| RXR | |
| 9-cis RA | Binding to an NR partner (e.g., FXR, LXR, PPAR, RAR, TR, or VDR) promotes recruitment of cofactors and HATs that lead to transcriptional activation (159) |
| Lithocholic acid | |
| Phytanic acid | |
| VDR | |
| Vitamin D | Binding to VDR influences recruitment of coactivators or repressors and transcription of target genes (160–162) |
| Curcumin | Activates heterodimer formation with RXR and recruitment of coactivator SRC-1 (163) |
| FXR | |
| BAs | Increase interaction with NCoA6 (LXXLL motif) (126) |
| EGCG | Inhibits recruitment of coactivator SRC-2 to FXR and transcription of target genes in the intestine (7) |
| LXR | |
| Resveratrol | Increases RNA polymerase recruitment to the LXR promoter (164) |
| EGCG | Reduces expression of LXR in 3T3-LI liver cells (165) |
| Genistein | Increases promoter activity in rat liver, leading to insulin sensitization and improved lipid homeostasis (166) |
AcH4, acetylated histone-4; AhR, aromatic hydrocarbon receptor; AR, androgen receptor; BA, bile acid; BRCA-1, breast cancer-1; COX-2, cyclooxygenase-2; CYP1A1, cytochrome P450, family 1, subfamily A, polypeptide 1; DIM, diindolylmethane; DNMT, DNA methyltransferase; EGCG, epigallocatechin 3-O-gallate; ER, estrogen receptor; FXR, farnesoid X receptor; HAT, histone acetyltransferase; HDAC, histone deacetylase; hTERT, human telomerase reverse transcriptase; I3C, indole-3-carbinol; LXR, liver X receptor; LXXLL, L indicates leucine and X indicates any amino acid; miR-34a, microRNA-34a; NCoA6, nuclear receptor coactivator 6; NR, nuclear receptor; RA, retinoic acid; RAR, retinoic acid receptor; RXR, retinoid X receptor; Sp1, specificity protein 1; SRC-1, steroid receptor coactivator-1; SRC-2, SRC-1, steroid receptor coactivator-2; TR, thyroid receptor; VDR, vitamin D receptor; XRE, xenobiotic response element.