Abstract：
Phenanthrene (Phe) is a commonly occurring polycyclic aromatic hydrocarbon (PAH) found in various food sources and drinking water. Previous studies have shown that long-term exposure to Phe in male mice leads to insulin resistance in a dose-dependent manner. However, the effect of Phe on glucose homeostasis in female mice remains unknown. To address this knowledge gap, female Kunming mice were exposed to Phe through their drinking water at concentrations of 0.05, 0.5, and 5 ng/mL. After 270 d of exposure, we surprisingly discovered a low-dose effect of Phe on insulin resistance in female mice, which differed from the effect observed in male mice and showed sexual dimorphism. Specifically, insulin resistance was only observed in the 0.05 ng/mL treatment, and this low-dose effect was also reflected in the concentration of Phe in white adipose tissue (WAT). Differences in metabolic enzyme activities in the liver may potentially explain this effect. The observed sexual dimorphism in Phe exposure could be attributed to variations in estrogen (E2) level and estrogen receptor beta (ERβ) expression in WAT. These findings highlight the association between environmental factors and the development of insulin resistance, emphasizing the pathogenic effect of even low doses of Phe. Moreover, sex dependent-effect should be given more attention when studying the toxic effects of environmental pollutants.
摘要：
菲（Phe）是在各种食物来源和饮用水中发现的常见多环芳烃（PAH）。先前的研究表明，雄性小鼠长期暴露于Phe会以剂量依赖性方式导致胰岛素抵抗。然而,Phe对雌性小鼠葡萄糖稳态的影响尚不清楚。为了解决这个知识差距，雌性昆明小鼠通过其浓度为0.05、0.5和5ng/mL的饮用水暴露于Phe。暴露270d后，我们令人惊讶地发现，在雌性小鼠中，Phe对胰岛素抵抗的低剂量作用，这与在雄性小鼠中观察到的效果不同，并显示性二态性。具体来说,仅在0.05ng/mL治疗中观察到胰岛素抵抗，这种低剂量效应也反映在白色脂肪组织（WAT）中Phe的浓度上。肝脏中代谢酶活性的差异可能解释了这种作用。在Phe暴露中观察到的性二态可归因于WAT中雌激素（E2）水平和雌激素受体β（ERβ）表达的变化。这些发现强调了环境因素与胰岛素抵抗发展之间的关联，强调即使低剂量的Phe的致病作用。此外，在研究环境污染物的毒性作用时，应给予更多的关注。
