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. Author manuscript; available in PMC: 2018 Feb 1.
Published in final edited form as: Nat Rev Endocrinol. 2017 May 19;13(8):445–457. doi: 10.1038/nrendo.2017.42

Figure 3. NR-mediated effects of EDCs on fatty liver development.

Figure 3

a The NR1 subfamily of nuclear hormone receptors (NRs) heterodimerize with retinoid X receptors (RXRs) to either promote (pregnane X receptor (PXR) or liver X receptor (LXR)) or inhibit (peroxisome proliferator-activated receptors (PPARs), constitutive androstane receptor (CAR), farnesoid X receptor (FXR), and thyroid receptors (TRs)) hepatic steatosis upon binding their naturally occurring agonist ligands. Select endocrine-disrupting chemicals (EDCs) known to bind these NRs and affect their activity are depicted at the bottom of the figure. For example, tributyltin (TBT) binding RXR–PPAR enhances steatosis, unlike natural free fatty acid ligands. LXR activates lipogenic genes upon binding its natural ligands (oxysterols) and promotes steatosis, but whether its activity is modulated by specific EDCs is currently unclear. b Another major class of NRs that bind EDCs is the steroid receptors such as the androgen receptor (AR), glucocorticoid receptor (GR) and oestrogen receptor (ER). Steroid hormones can either increase (glucocorticoid) or decrease (oestrogen and androgen) hepatic steatosis. Select EDCs known to bind these NRs and affect their activity are depicted at the bottom of the figure. c Aryl hydrocarbon receptor (AhR) represents the third major NR effector of EDC action in the liver. AhR binds EDCs, such as dioxins and polychlorinated biphenyls (PCBs), leading to enhanced steatosis. BPA, bisphenol A; DDE, dichlorodiphenyldichloroethylene; DDT, dichlorodiphenyltrichloroethane; DEHP, di-2-ethylhexyl phthalate; PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonate.