Implications of peroxisome proliferator-activated receptor gamma (PPARY) with the intersection of organophosphate flame retardants and diet-induced obesity in adult mice

ABSTRACT

Previously, organophosphate flame retardants (OPFRs) were demonstrated to dysregulate homeostatic parameters of energy regulation within an adult mouse model of diet-induced obesity. Using the same OPFR mixture consisting of 1 mg/kg/day of each triphenyl phosphate, tricresyl phosphate, and tris(1,3-dichloro-2-propyl)phosphate, the current study examined the role of peroxisome proliferator-activated receptor gamma (PPARγ) in OPFR-induced disruption by utilizing mice with brain-specific deletion of PPARγ (PPARγKO) fed either a low-fat diet (LFD) or high-fat diet (HFD). Body weight and composition, feeding behavior, glucose and insulin tolerance, circulating peptide hormones, and expression of hypothalamic genes associated with energy homeostasis were recorded. When fed HFD, the effects of OPFR on body weight and feeding behavior observed in the previous wild-type (WT) study were absent in mice lacking neuronal PPARγ. This posits PPARγ as an important target for eliciting OPFR disruption in a diet-induced obesity model. Interestingly, female PPARγKO mice, but not males, experienced many novel OPFR effects not noted in WT mice, including decreased fat mass, altered feeding behavior and efficiency, improved insulin sensitivity, elevated plasma ghrelin and hypothalamic expression of its receptor. Taken together, these data suggest both direct roles for PPARγ in OPFR disruption of obese mice and indirect sensitization of pathways alternative to PPARγ when neuronal expression is deleted.

KEYWORDS:

• Flame retardants
• metabolism
• ingestive behavior
• diet-induced obesity
• ppar-gamma

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].