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饮食诱导肥胖和有机磷阻燃剂暴露对成年雄性和雌性小鼠能量平衡的相互作用。

The interactions of diet-induced obesity and organophosphate flame retardant exposure on energy homeostasis in adult male and female mice.

机构信息

Joint Graduate Program in Toxicology, Rutgers, the State University of New Jersey , Piscataway, NJ, USA.

Department of Animal Sciences, School of Environmental & Biological Sciences, Rutgers, the State University of New Jersey , New Brunswick, NJ, USA.

出版信息

J Toxicol Environ Health A. 2020 Jun 17;83(11-12):438-455. doi: 10.1080/15287394.2020.1777235. Epub 2020 Jun 16.

Abstract

Previously, sex-dependent alterations in energy homeostasis were reported in adult mice fed a standard chow attributed to exposure to a mixture of organophosphate flame retardants (OPFRs) via estrogen receptors (ERα). In this study, adult male and female mice (C57BL/6J; Taconic) were treated with the same mixture of OPFRs (1 mg/kg each of tricresyl phosphate (TCP), triphenyl phosphate (TPP), and tris(1-3-dichloro-2propyl)phosphate (TDCPP)) for 7 weeks on a low-fat diet (LFD, 10% kcal fat) or a high fat (HFD, 45% kcal fat) in a diet-induced obesity model. Consistent with our previous observations, OPFRs altered weight gain in males, differentially with diet, while females remained unaffected. OPFR treatment also revealed sex-dependent perturbations in metabolic activity. During the night (approximately 0100-0400 hr), males exhibited elevated activity and oxygen consumption, while in females these parameters were decreased, irrespective of diet. OPFR disrupted feeding behavior and abolished diurnal water intake patterns in females while increasing nighttime fluid consumption in males. Despite no marked effect of OPFRs on glucose or insulin tolerance, OPFR treatment altered circulating insulin and leptin in females and ghrelin in males. Data indicate that adult OPFR exposure might influence, and perhaps exacerbate, the effects of diet-induced obesity in adult mice by altering activity, ingestive behavior, and metabolism.

摘要

先前有研究报道,标准饲料喂养的成年雄性和雌性小鼠的能量平衡存在性别依赖性改变,这种改变归因于通过雌激素受体(ERα)暴露于混合有机磷阻燃剂(OPFRs)。在这项研究中,成年雄性和雌性小鼠(C57BL/6J;Taconic)接受了相同的 OPFR 混合物(三氯乙基磷酸酯(TCP)、磷酸三苯酯(TPP)和三(1-3-二氯-2-丙基)磷酸酯(TDCPP),每种 1 毫克/千克),分别在低脂肪饮食(LFD,10%卡路里脂肪)或高脂肪饮食(HFD,45%卡路里脂肪)下进行了 7 周的饮食诱导肥胖模型处理。与我们之前的观察结果一致,OPFRs 改变了雄性的体重增加,且这种改变与饮食有关,而雌性则不受影响。OPFR 处理还揭示了代谢活性的性别依赖性失调。在夜间(大约 0100-0400 小时),雄性表现出更高的活动和耗氧量,而雌性则降低了这些参数,而与饮食无关。OPFR 破坏了雌性的摄食行为和昼夜饮水模式,并增加了雄性的夜间液体消耗。尽管 OPFRs 对葡萄糖或胰岛素耐量没有明显影响,但 OPFR 处理改变了雌性的循环胰岛素和瘦素水平,以及雄性的胃饥饿素水平。数据表明,成年 OPFR 暴露可能通过改变活动、摄食行为和代谢来影响,甚至可能加剧成年肥胖小鼠的饮食诱导肥胖的影响。

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