. Author manuscript; available in PMC: 2020 Sep 1.

Published in final edited form as: Curr Environ Health Rep. 2019 Sep;6(3):80–94. doi: 10.1007/s40572-019-00232-w

Table 2.

Main targets and modes of action for volatile organic compounds and persistent organic pollutants in fatty liver disease.

Target Category	Target/Receptor	Outcomes/Processes	Chemical Group	References
Hepatic Nuclear Receptors	PPARs	-steatosis -immuno-toxicity -apoptosis	PFOA/PFOS VOCs	[73, 162, 163] [33]
Hepatic Nuclear Receptors	PXR, CAR, FXR	-lipogenesis & decreased fatty acid oxidation -decreased gluconeogenesis -hepatokine dysregulation -altered cholesterol/bile acid metabolism	PCBs	[23, 67, 12]
Sex Steroid Receptors	ERα, ERβ, AR	-endocrine-metabolic disruption	PCBs, PFAS	[164, 165]
Other Receptors	AhR	-lipid accumulation -inflammation and oxidative stress -hepatokine dysregulation -gut microbiome alterations	PCBs, TCDD	[62, 12, 166, 93, 167, 63, 60]
Other Receptors	EGFR	-EGFR signaling disruption -diminished HNF4A -altered insulin production	PCBs, OCPs	[19, 17]
Energy Sensors/Regulators	CREB	-disruption of hepatic energy ‘sensing’	Dioxin-like PCBs	[57, 168]
Energy Sensors/Regulators	AMPK, mTOR,	-glycogen depletion -lipid accumulation	VOCs	[27, 29]
Organelles/Protein Complex	Endoplasmic reticulum, Mitochondria, Inflammasome	-ER and oxidative stress -carbonyl stress -inflammation -enhanced neutrophil extracellular trap formation	VOCs	[4, 14, 28, 43, 44, 54].
Antioxidant Responses	NRF2	-Reactive oxygen species generation -oxidative stress	PCBs, VOCs	[4, 20]