Organophosphorus Flame Retardants Inhibit Specific Liver Carboxylesterases and Cause Serum Hypertriglyceridemia

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.