Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Organophosphate Flame Retardants Excite Arcuate Melanocortin Circuitry and Increase Neuronal Sensitivity to Ghrelin in Adult Mice.

Authors: Vail, Gwyndolin M; Roepke, Troy A

Published In Endocrinology, (2020 11 01)

Abstract: Organophosphate flame retardants (OPFRs) are a class of chemicals that have become near ubiquitous in the modern environment. While OPFRs provide valuable protection against flammability of household items, they are increasingly implicated as an endocrine disrupting chemical (EDC). We previously reported that exposure to a mixture of OPFRs causes sex-dependent disruptions of energy homeostasis through alterations in ingestive behavior and activity in adult mice. Because feeding behavior and energy expenditure are largely coordinated by the hypothalamus, we hypothesized that OPFR disruption of energy homeostasis may occur through EDC action on melanocortin circuitry within the arcuate nucleus. To this end, we exposed male and female transgenic mice expressing green fluorescent protein in either neuropeptide Y (NPY) or proopiomelanocortin (POMC) neurons to a common mixture of OPFRs (triphenyl phosphate, tricresyl phosphate, and tris(1,3-dichloro-2-propyl)phosphate; each 1 mg/kg bodyweight/day) for 4 weeks. We then electrophysiologically examined neuronal properties using whole-cell patch clamp technique. OPFR exposure depolarized the resting membrane of NPY neurons and dampened a hyperpolarizing K+ current known as the M-current within the same neurons from female mice. These neurons were further demonstrated to have increased sensitivity to ghrelin excitation, which more potently reduced the M-current in OPFR-exposed females. POMC neurons from female mice exhibited elevated baseline excitability and are indicated in receiving greater excitatory synaptic input when exposed to OPFRs. Together, these data support a sex-selective effect of OPFRs to increase neuronal output from the melanocortin circuitry governing feeding behavior and energy expenditure, and give reason for further examination of OPFR impact on human health.

PubMed ID: 32961558 Exiting the NIEHS site

MeSH Terms: Animals; Arcuate Nucleus of Hypothalamus/drug effects*; Arcuate Nucleus of Hypothalamus/metabolism; Drug Resistance/drug effects; Endocrine Disruptors/pharmacology; Female; Flame Retardants/pharmacology*; Ghrelin/pharmacology*; Hypothalamus/metabolism; Male; Melanocortins/metabolism*; Mice; Mice, Transgenic; Nerve Net/drug effects*; Nerve Net/physiology; Neurons/drug effects*; Neurons/metabolism; Neuropeptide Y/genetics; Neuropeptide Y/metabolism; Organophosphates/pharmacology; Pro-Opiomelanocortin/genetics; Pro-Opiomelanocortin/metabolism

Back
to Top