Figures & data
Notes: Lipophilic POPs enter into cells and bind to the AhR in the cytoplasm where it is associated with a complex of proteins that include hsp90, p23 and XAP2. After binding to POPs, AhR dissociates from its chaperone complex and then translocates into nucleus where it forms a heterodimer with ARNT and binds to DRE elements in the promoters of target genes to induce their transcription, including members of the cytochrome P450 family. While expression of the target genes produce phase I metabolizing enzymes that attack POPs and degrade them (red arrow), they also produce cytotoxic metabolites that may have harmful effects on cells (green arrows), the blue arrows indicate the flow of activity that occurs upon activation of the receptor.
Abbreviations: AhR, aryl hydrocarbon receptor; POPs, persistent organic pollutants; ARNT, aryl hydrocarbon nuclear transporter; DRE, dioxin response element.
Abbreviations: AhR, aryl hydrocarbon receptor; POPs, persistent organic pollutants; ARNT, aryl hydrocarbon nuclear transporter; DRE, dioxin response element.
Notes: AhR activation by POPs and/or high-fat diet directly targets certain genes controlling glucose and lipid metabolism in the liver and adipose tissue, thereby directly contributing to the development of metabolic disorders. In adipose tissue, AhR activation targets adipogenesis and lipolysis, acting to inhibit both processes. In adipose tissue, AhR suppresses mTORC, which decreases AKT activity and inhibits PPARγ levels, ultimately leading to decreased differentiation of pre-adipocytes. The reduction in adipocyte numbers provides fewer adult adipocytes for capturing lipids. Under HFD conditions, adipocytes become hypertrophied and ultimately overwhelmed; lipid then accumulates in other organs and adipose tissue becomes inflamed. In the liver, AhR activation promotes CD36, which enhances lipid uptake by the liver. AhR activation also suppresses PPARα, leading to decreased β-oxidation and FA metabolism. Finally, AhR may regulate FGF21, which has a role in regulation of systemic metabolism through effects on adipose tissue function.
Abbreviations: AhR, aryl hydrocarbon receptor; POPs, persistent organic pollutants; mTORC, mammalian target of rapamycin complex; PPAR, peroxisome proliferator-activated receptor; HFD, high-fat diet; FA, fatty acid; FGF21, fibroblast growth factor 21; C/EBP, CCAAT/enhancer-binding protein; ATGL, adipose triglyceride lipase; DAG, diacylglycerol; HSL, hormone-sensitive lipase; MAG, monoacylglycerol; MGL, monoglyceride lipase; TG, triglycerides; FFA, free fatty acids; TAG, triacyl glycerol.
Abbreviations: AhR, aryl hydrocarbon receptor; POPs, persistent organic pollutants; mTORC, mammalian target of rapamycin complex; PPAR, peroxisome proliferator-activated receptor; HFD, high-fat diet; FA, fatty acid; FGF21, fibroblast growth factor 21; C/EBP, CCAAT/enhancer-binding protein; ATGL, adipose triglyceride lipase; DAG, diacylglycerol; HSL, hormone-sensitive lipase; MAG, monoacylglycerol; MGL, monoglyceride lipase; TG, triglycerides; FFA, free fatty acids; TAG, triacyl glycerol.