Cao Hao, Wiemerslage Lyle, Marttila Petra S K, Williams Michael J, Schiöth Helgi B
Unit of Functional pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
Basic Clin Pharmacol Toxicol. 2016 Sep;119(3):309-16. doi: 10.1111/bcpt.12587. Epub 2016 Apr 25.
Bis-(2-ethylhexyl) phthalate (DEHP) is one of the most widely used plasticizers, and human beings are exposed to DEHP via polyvinyl chloride (PVC) materials, medical equipment and even drinking water. While DEHP has been implicated to influence metabolism and endocrine functions, important questions remain about the molecular mechanisms of these effects. We employed the model organism Drosophila melanogaster and examined physiological, molecular and behavioural effects from DEHP-contaminated food. We found that DEHP, at levels comparable to human exposure, made male flies more resistant to starvation and increased lipid levels, while decreasing circulating carbohydrates. Moreover, DEHP-fed male flies had higher expression levels of an insulin-like peptide known to regulate metabolism, as well as the insulin receptor. Our results suggest that long-term DEHP feeding may induce diabetes-like dysfunctions. These findings provide a molecular background of how DEHP may have detrimental effects on metabolic functions.
邻苯二甲酸二(2-乙基己基)酯(DEHP)是使用最广泛的增塑剂之一,人类通过聚氯乙烯(PVC)材料、医疗设备甚至饮用水接触到DEHP。虽然DEHP被认为会影响新陈代谢和内分泌功能,但这些影响的分子机制仍存在重要问题。我们使用模式生物黑腹果蝇,研究了受DEHP污染的食物对其生理、分子和行为的影响。我们发现,与人类接触水平相当的DEHP使雄性果蝇对饥饿更具抵抗力,脂质水平升高,同时循环碳水化合物减少。此外,喂食DEHP的雄性果蝇中,一种已知可调节新陈代谢的胰岛素样肽以及胰岛素受体的表达水平更高。我们的结果表明,长期喂食DEHP可能会诱发类似糖尿病的功能障碍。这些发现为DEHP如何对代谢功能产生有害影响提供了分子背景。