Bisphenol A Promotes Adiposity and Inflammation in a Nonmonotonic Dose-response Way in 5-week-old Male and Female C57BL/6J Mice Fed a Low-calorie Diet
Bisphenol A Promotes Adiposity and Inflammation in a Nonmonotonic Dose-response Way in 5-week-old Male and Female C57BL/6J Mice Fed a Low-calorie Diet
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双酚 A 以非单调剂量反应方式促进低热量饮食的 5 周龄雄性和雌性 C57BL/6J 小鼠的肥胖和炎症。
DOI：
10.1210/en.2015-1926
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发表时间：
2016
期刊：
影响因子：
4.8
通讯作者：
Ning Guang
中科院分区：
文献类型：
--
作者：
Yang Minglan;Chen Maopei;Wang Jiqiu;Xu Min;Sun Jichao;Ding Lin;Lv Xiaofei;Ma Qinyun;Bi Yufang;Liu Ruixin;Hong Jie;Ning Guang
越来越多的流行病学研究表明，双酚A（BPA）与肥胖和代谢紊乱呈正相关。然而，BPA对肥胖的作用机制在很大程度上仍然未知。在这项研究中，我们发现，5周龄的雄性和雌性C57 BL/6 J小鼠暴露于四种剂量的BPA（5，50，500和5000 μg/kg/d）30天，当喂食普通饲料时，体重和脂肪量以非单调的剂量依赖性方式显著增加。即使在最低浓度（5μg/kg/d）下也会发生这种效应，低于BPA的每日可耐受摄入量50 μg/kg/d。然而，在喂食高脂肪饮食的雄性或雌性小鼠中没有观察到体重和脂肪量的显着差异，这表明BPA可能与饮食相互作用，促进肥胖风险。体外研究表明，BPA处理驱动白色脂肪祖细胞从基质血管组分分化，部分通过糖皮质激素受体。双酚A暴露增加循环炎症因子和局部炎症白色脂肪组织在两个性别喂养的普通饲料，但不高脂饮食。我们进一步发现，BPA浓度与瘦女性受试者（体重指数< 23.0 kg/m2）中循环炎症因子（包括瘦素和TNFα）的增加相关，但与瘦男性受试者或超重/肥胖受试者（体重指数> 25.0 kg/m2）中的BPA浓度无关。总之，我们证明了BPA对5周龄小鼠肥胖和慢性炎症的非单调剂量效应，这与热量摄取有关。
A growing body of epidemiological research show that Bisphenol A (BPA) is positively correlated with obesity and metabolic disorders. However, the mechanisms of BPA on adiposity remain largely unknown. In this study, we found that 5-week-old male and female C57BL/6J mice exposed to four dosages of BPA (5, 50, 500, and 5000 μg/kg/d) by oral intake for 30 days showed significantly increased body weight and fat mass in a nonmonotonic dose-dependent manner when fed a chow diet. The effect occurred even at the lowest concentration (5μg/kg/d), lower than the tolerable daily intake of 50 μg/kg/day for BPA. However, no significant difference in body weight and fat mass was observed in either male or female mice fed a high-fat diet, suggesting that BPA may interact with diet in promoting obesity risk. In vitro study showed that BPA treatment drives the differentiation of white adipocyte progenitors from the stromal vascular fraction, partially through glucocorticoid receptor. BPA exposure increased circulating inflammatory factors and the local inflammation in white adipose tissues in both genders fed a chow diet, but not under high-fat diet. We further found that BPA concentration was associated with increased circulating inflammatory factors, including leptin and TNFα, in lean female subjects (body mass index < 23.0 kg/m(2)) but not in lean male subjects or in both sexes of overweight/obese subjects (body mass index > 25.0 kg/m(2)). In conclusion, we demonstrated the nonmonotonic dose effects of BPA on adiposity and chronic inflammation in 5-week-old mice, which is related to caloric uptake.