Short-term treatment with bisphenol-A leads to metabolic abnormalities in adult male mice.
Short-term treatment with bisphenol-A leads to metabolic abnormalities in adult male mice.
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DOI：
10.1371/journal.pone.0033814
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Nadal A
中科院分区：
文献类型：
--
作者：
Batista TM;Alonso-Magdalena P;Vieira E;Amaral ME;Cederroth CR;Nef S;Quesada I;Carneiro EM;Nadal A
双酚A(BPA)是聚碳酸酯塑料生产中使用最广泛的内分泌干扰物(EDC)。尽管有证据表明，暴露于双酚A是胰岛素抵抗的危险因素，但双酚A对全身新陈代谢和胰岛素敏感组织的作用仍不清楚。本工作的目的是研究低剂量双酚A对成年小鼠胰岛素敏感外周组织和全身代谢的影响。成年小鼠皮下注射100µg/kg双酚A或赋形剂，连续8天。用体内间接量热法测定全身能量平衡。用免疫印迹法检测胰岛素信号转导。用双酚A治疗的小鼠有胰岛素抵抗，并增加了葡萄糖刺激的胰岛素释放。与对照组相比，服用双酚A的小鼠进食量减少，体温和活动能力降低。在骨骼肌中，双酚A处理的小鼠胰岛素刺激的胰岛素受体β亚单位的酪氨酸磷酸化受到损害。这种损害与Thr308残基上胰岛素刺激的Akt磷酸化减少有关。BPA对骨骼肌和肝脏IRS-1蛋白表达均有上调作用。在BPA处理的小鼠的骨骼肌中，丝裂原活化蛋白激酶(MAPK)信号通路也受到了损害。在肝脏中，双酚A的作用强度较小，胰岛素刺激的胰岛素受体β亚单位的酪氨酸磷酸化程度降低。总而言之，短期服用低剂量双酚A会减缓全身能量代谢，并扰乱周围组织中的胰岛素信号。因此，我们的发现支持双酚A可以被认为是2型糖尿病发展的危险因素的观点。
Bisphenol-A (BPA) is one of the most widespread endocrine disrupting chemicals (EDC) used as the base compound in the manufacture of polycarbonate plastics. Although evidence points to consider exposure to BPA as a risk factor for insulin resistance, its actions on whole body metabolism and on insulin-sensitive tissues are still unclear. The aim of the present work was to study the effects of low doses of BPA in insulin-sensitive peripheral tissues and whole body metabolism in adult mice. Adult mice were treated with subcutaneous injection of 100 µg/kg BPA or vehicle for 8 days. Whole body energy homeostasis was assessed with in vivo indirect calorimetry. Insulin signaling assays were conducted by western blot analysis. Mice treated with BPA were insulin resistant and had increased glucose-stimulated insulin release. BPA-treated mice had decreased food intake, lower body temperature and locomotor activity compared to control. In skeletal muscle, insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit was impaired in BPA-treated mice. This impairment was associated with a reduced insulin-stimulated Akt phosphorylation in the Thr308 residue. Both skeletal muscle and liver displayed an upregulation of IRS-1 protein by BPA. The mitogen-activated protein kinase (MAPK) signaling pathway was also impaired in the skeletal muscle from BPA-treated mice. In the liver, BPA effects were of lesser intensity with decreased insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit. In conclusion, short-term treatment with low doses of BPA slows down whole body energy metabolism and disrupts insulin signaling in peripheral tissues. Thus, our findings support the notion that BPA can be considered a risk factor for the development of type 2 diabetes.
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影响因子：
15.9
作者：
Cusi, K;Maezono, K;Mandarino, LJ
通讯作者：
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影响因子：
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作者：
Alonso-Magdalena P;Vieira E;Soriano S;Menes L;Burks D;Quesada I;Nadal A
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雌激素受体ERα调节胰腺胰岛素含量。
影响因子：
3.7
作者：
Alonso-Magdalena, Paloma;Ropero, Ana B.;Carrera, M. Pilar;Cederroth, Christopher R.;Baquie, Mathurin;Gauthier, Benoit R.;Nef, Serge;Stefani, Enrico;Nadal, Angel
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Nadal, Angel
在风险评估中，对鱼类生物标志物中内分泌干扰的筛查和测试是“路标”，而不是“交通信号灯”。
影响因子：
10.4
作者：
Hutchinson, Thomas H;Ankley, Gerald T;Segner, Helmut;Tyler, Charles R
通讯作者：
Tyler, Charles R
影响因子：
7.7
作者：
Karlsson, HKR;Zierath, JR;Wallberg-Henriksson, H
通讯作者：
Wallberg-Henriksson, H