Organophosphorus Flame Retardants Impair Intracellular Lipid Metabolic Function in Human Hepatocellular Cells

Abstract

Organophosphorus flame retardants (OPFRs), a replacement for brominated flame retardants, have gradually been accepted as endocrine disrupting chemicals (EDCs). Recently, evidence has shown that these EDCs could cause chronic health problems, such as obesity, and referred to as metabolic disruptors. However, the disturbance to lipid metabolism caused by OPFRs remains poorly understood, especially at biological molecular levels. Herein, we used the human hepatocellular cells (HepG2) to study the lipid metabolism disruption caused by nine OPFRs (halogenated-, aryl-, and alkyl-containing). All the tested OPFRs, excluding the long carbon chain alkyl-OPFRs, could cause intracellular triglyceride (TG) and/or total cholesterol (TC) accumulation. In detail, aryl-OPFRs (TPhP and TCP) induced both TC and TG deposition. Halogenated-OPFRs (TCEP, TBPP, TDCPP, and TCPP) induced intracellular TG accumulation, and only TDCPP also induced TC accumulation. Furthermore, TPhP induced lipid accumulation through regulation genes encoding proteins involved in fatty acid β-oxidation, lipid, and fatty acid synthesis. All the halogenated-OPFRs cause TG accumulation only, enacted through β-oxidation rather than lipid synthesis. TPhP and TDCPP induced TC accumulation through both PPARγ and srebp2 signaling. Mitochondrial dysfunction including decreased oxygen consumption rate and ATP content may also contribute to lipid metabolic disruption by the tested OPFRs. Our data indicated that halogenated- and aryl-OPFRs may not be safe candidates, and further information should be made available as potential for, as well as the mechanism of, metabolic disruption. And long carbon chain alkyl-OPFRs may be safer than the other two groups.

Associations between the exposure to organophosphate flame retardants during early pregnancy and the risk of spontaneous abortion based on metabolomics combined with tandem mass spectrometry

“…Metabolomics studies the role of small-molecule metabolites in pregnancy and pregnancy-related diseases from a holistic perspective. It has been shown that different OPFRs cause the cellular metabolism disorder in different ways, including oxidative stress and the equilibrium of osmotic pressure, also caused mitochondrial dysfunction (17). In addition, cells exposed to OPFRs may also induce apoptosis through autophagy.…”

Ambient fine particulate matter induces inflammatory responses of vascular endothelial cells through activating TLR-mediated pathway

“…The protein isolation, the protein concentration determination, and the Western blot were performed as in our previous reports (Hao et al, 2019). TLR2 and TLR4 antibodies were from ImmunoWay Biotechnologies (San Diego, California, USA).…”

Structure Dependent Determination of Organophosphate Targets in Mammalian Tissues Using Activity-Based Protein Profiling

“…The probes did not label all of these targets in the same manner (Figure 5), indicating selectivity for some proteins depending on probe structure and reactivity. Given the importance of lipases and lipid signaling in brain, [49][50][51] the effects of OPs on lipid metabolism has been proposed as a major contributing factor to the long-term negative impacts of OP exposure on development and cognitive function. 52 Our OP ABPs represent new tools for profiling these important enzymes in the brain and other tissues that react with different OP structures.…”