MassIVE MSV000098555

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Exposure to a persistent organic pollutant mixture and sex-specific steatotic liver disease

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Description

A 2DLC-(TMTPro)-MS workflow was used to examine hepatic exposure to persistent organic pollutants (POPs) with steatotic liver disease (SLD). The goal was to determine the sex-specific impact of POPs on SLD and identify underlying sex-specific mechanisms. Male and female C57BL/6 mice were fed either a western (WD) or control diet (CD) and exposed to vehicle control or a POP mixture (PCB 126 and chlordane) over a 12-week period. A second group of intact female or ovariectomized (OVX) mice were exposed to the same POP mixture or vehicle control for 2 weeks. Compared to their diet- and sex-matched controls, WD-fed female mice exposed to the POP mixture exhibited steatosis and these observations were absent in males. Chemical exposure, irrespective of sex and diet, activated hepatic xenobiotic receptors, namely the AHR (Cyp1a1/Cyp1a2 induction) and CAR (Cyp1b10 induction), more robust CAR activation was observed in CD-fed females. This group also showed decreased liver gene expression for estrogen sulfotransferase (Sult1e1), a key enzyme in estrogen metabolism. Female mice exposed to the POP mixture were more susceptible to toxicant-associated SLD. Our findings emphasized the significance of considering biological sex in assessing disease risk [doi:10.25345/C51R6ND0X] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: liver ; organic pollutant exposure ; TMTPro ; DatasetType:Proteomics

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Principal Investigators:
(in alphabetical order) 		Michael L. Merchant, PhD, University of Louisville, USA
Submitting User: mmerchant
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