Persistent organic pollutants such as organophosphate flame retardants (OPFRs) can accumulate in the body and interact with nuclear receptors that control energy homeostasis. One sensitive window of exposure is during development, either in utero or neonatal. Therefore, we investigated if maternal exposure to a mixture of OPFRs alters metabolism on a low‐fat diet (LFD) or a high‐fat diet (HFD) in both male and female offspring. Wild‐type C57Bl/6J dams were orally dosed with vehicle (sesame oil) or an OPFR mixture (1 mg/kg each of tris(1,3‐dichloro‐2‐propyl)phosphate, triphenyl phosphate, and tricresyl phosphate) from gestation day 7 to postnatal day 14. After weaning, pups were fed LFD or HFD. To assess metabolism, we measured body weight and food intake weekly and determined body composition, metabolism, activity, and glucose homeostasis at 6 months of age. Although maternal OPFR exposure did not alter body weight or adiposity, OPFR exposure altered substrate utilization and energy expenditure depending on diet in both sexes. Systolic and diastolic blood pressure was increased by OPFR in male offspring. OPFR exposure interacted with HFD to increase fasting glucose in females and alter glucose and insulin tolerance in male offspring. Plasma leptin was reduced in male and female offspring when fed HFD, whereas liver expression of Pepck was increased in females and Esr1 (estrogen receptor α) was increased in both sex. The physiological implications indicate maternal exposure to OPFRs programs peripheral organs including the liver and adipose tissue, in a sex‐dependent manner, thus changing the response to an obesogenic diet and altering adult offspring energy homeostasis.

中文翻译：

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母体有机磷酸盐阻燃剂暴露以两性二态的方式改变小鼠后代的能量和葡萄糖稳态

有机磷阻燃剂 (OPFR) 等持久性有机污染物会在体内积聚，并与控制能量稳态的核受体相互作用。一个敏感的暴露窗口是在发育过程中，无论是在子宫内还是在新生儿期。因此，我们调查了母体暴露于 OPFRs 混合物是否会改变雄性和雌性后代在低脂饮食 (LFD) 或高脂饮食 (HFD) 中的新陈代谢。野生型 C57Bl/6J 水坝从妊娠期开始口服赋形剂（芝麻油）或 OPFR 混合物（磷酸三（1,3-二氯-2-丙基）、磷酸三苯酯和磷酸三甲苯酯各 1 mg/kg）第 7 天到出生后第 14 天。断奶后，幼犬喂食 LFD 或 HFD。为了评估新陈代谢，我们每周测量体重和食物摄入量，并确定身体成分、新陈代谢、活动、和 6 个月大时的葡萄糖稳态。虽然母体 OPFR 暴露不会改变体重或肥胖，但 OPFR 暴露会改变底物利用和能量消耗，这取决于两性的饮食。OPFR 使雄性后代的收缩压和舒张压升高。OPFR 暴露与 HFD 相互作用以增加雌性的空腹血糖并改变雄性后代的葡萄糖和胰岛素耐受性。当喂食 HFD 时，雄性和雌性后代的血浆瘦素降低，而肝脏表达 OPFR 暴露与 HFD 相互作用以增加雌性的空腹血糖并改变雄性后代的葡萄糖和胰岛素耐受性。当喂食 HFD 时，雄性和雌性后代的血浆瘦素降低，而肝脏表达 OPFR 暴露与 HFD 相互作用以增加雌性的空腹血糖并改变雄性后代的葡萄糖和胰岛素耐受性。当喂食 HFD 时，雄性和雌性后代的血浆瘦素降低，而肝脏表达Pepck 在女性中增加，而Esr1（雌激素受体 α）在两种性别中都增加。生理学意义表明，母体暴露于 OPFRs 会以性别依赖的方式对包括肝脏和脂肪组织在内的外周器官进行编程，从而改变对致肥胖饮食的反应并改变成年后代的能量稳态。