Implications of estrogen receptor alpha (ERa) with the intersection of organophosphate flame retardants and diet-induced obesity in adult mice

ABSTRACT

Previously, organophosphate flame retardants (OPFRs) were found to produce intersecting disruptions of energy homeostasis using an adult mouse model of diet-induced obesity. Using the same mixture consisting of 1 mg/kg/day of each triphenyl phosphate, tricresyl phosphate, and tris(1,3-dichloro-2-propyl)phosphate, the current study aimed to identify the role of estrogen receptor alpha (ERα) in OPFR-induced disruption, utilizing ERα knockout (ERαKO) mice fed either a low-fat diet (LFD) or high-fat diet (HFD). Body weight and composition, food intake patterns, glucose and insulin tolerance, circulating peptide hormones, and expression of hypothalamic genes associated with energy homeostasis were measured. When fed HFD, no marked direct effects of OPFR were observed in mice lacking ERα, suggesting a role for ERα in generating previously reported wildtype (WT) findings. Male ERαKO mice fed LFD experienced decreased feeding efficiency and altered insulin tolerance, whereas their female counterparts displayed less fat mass and circulating ghrelin when exposed to OPFRs. These effects were not noted in the previous WT study, indicating that loss of ERα may sensitize animals fed LFD to alternate pathways of endocrine disruption by OFPRs. Collectively, these data demonstrate both direct and indirect actions of OPFRs on ERα-mediated pathways governing energy homeostasis and support a growing body of evidence urging concern for risk of human exposure.

KEYWORDS:

• Flame retardants
• metabolism
• ingestive behavior
• diet-induced obesity
• er-alpha

Acknowledgments

This work was supported by the US Department of Agriculture–National Institute of Food and Agriculture (NJ06195, TAR) and the National Institutes of Health (R21ES027119, R01MH123544, and P30ES005022, TAR). SNW was funded by R21ES027119-S1 and GMV was funded, in part, by T32ES007148.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data Availability Statement

The data that support the findings of this study are available from the corresponding author, T.A. Roepke, upon reasonable request.

Additional information

Funding

This work was supported by the National Institute of Environmental Health Sciences [P30ES005022,R21ES027119,R21ES027119-S1,T32ES007148]; National Institute of Mental Health [R01MH123544]; USDA-NIFA [NJ06195].