title: Organophosphorus flame retardants inhibit specific liver carboxylesterases and cause serum hypertriglyceridemia.
abstract: Humans are prevalently exposed to organophosphorus flame retardants (OPFRs) contained in consumer products and electronics, though their toxicological effects and mechanisms remain poorly understood. We show here that OPFRs inhibit specific liver carboxylesterases (Ces) and cause altered hepatic lipid metabolism. Ablation of the OPFR target Ces1g has been previously linked to dyslipidemia in mice. Consistent with OPFR inhibition of Ces1g, we also observe OPFR-induced serum hypertriglyceridemia in mice. Our findings suggest novel toxicities that may arise from OPFR exposure and highlight the utility of chemoproteomic and metabolomic platforms in the toxicological characterization of environmental chemicals.
authors.affiliation: Department of Nutritional Sciences and Toxicology, University of California, Berkeley , 127 Morgan Hall, Berkeley, California 94720, United States.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Morris
authors.forename: Daniel
authors.initials: D
authors.lastname: Medina-Cleghorn
authors.forename: Ann
authors.initials: A
authors.lastname: Heslin
authors.forename: Sarah M
authors.initials: SM
authors.lastname: King
authors.forename: Joseph
authors.initials: J
authors.lastname: Orr
authors.forename: Melinda M
authors.initials: MM
authors.lastname: Mulvihill
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Krauss
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Nomura
mesh_terms: D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005411:Flame Retardants / Q000633:toxicity*; D057809:HEK293 Cells; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood* / Q000139:chemically induced*; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D009943:Organophosphorus Compounds / Q000633:toxicity*
chemical_list: D005411:Flame Retardants; D009943:Organophosphorus Compounds; D002265:Carboxylic Ester Hydrolases