Phenanthrene and its halogenated derivative inhibit adipogenesis and decrease peroxisome proliferator-activated receptor gamma (PPARγ) expression independently of aryl hydrocarbon receptor (AhR) activation

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are natural by-products of incomplete combustion of fossil fuels, wood, incinerator waste, and are also used in man-made dyes, plastics, and pesticides. Humans are mostly exposed to PAHs through air (ex. smoke inhalation), drinking water, and foods. Phenanthrene (Phe) is the most abundant PAH found in the environment, however there are very few studies that have examined either its systemic health effects or its effects on metabolism and adipogenesis. Halogenated-polycyclic aromatic hydrocarbons (HPAHs) are a class of PAHs that have a halogen bound to an aromatic ring of a PAH, leading to increased potency compared to their PAH derivatives and yet are studied even less so than PAHs. Extensive research on another PAH, and a strong AhR activator, Benzo[a]pyrene (BaP) showed that BaP inhibited adipogenesis in vitro amongst other effects. In this study, we proceeded to investigate the effects of Phe and its halogenated counterpart, 9-chloro-phenanthrene (9P), on adipogenesis in the 3 T3-L1 cell line. Our results show that Phe and 9P inhibited adipogenesis independently of AhR upregulation or activation, indicated by their inability to increase the expression of the AhR and its downstream target gene CYP1A1. We also show that both Phe and 9P decreased PPARγ mRNA, and more pronouncedly protein expression. Further, effects on expression of proteins in the insulin signaling pathway, and adipokines were also observed, suggesting a global effect on adipocyte function.