Brulport Axelle, Le Corre Ludovic, Chagnon Marie-Christine
Université de Bourgogne Franche-Comté, LNC UMR1231, F-21000 Dijon, France; AgroSup, LNC UMR1231, F-21000 Dijon, France; Nutrition Physiology and Toxicology Team (NUTox), INSERM, LNC UMR1231, F-21000 Dijon, France.
Université de Bourgogne Franche-Comté, LNC UMR1231, F-21000 Dijon, France; AgroSup, LNC UMR1231, F-21000 Dijon, France; Nutrition Physiology and Toxicology Team (NUTox), INSERM, LNC UMR1231, F-21000 Dijon, France.
Toxicology. 2017 Sep 1;390:43-52. doi: 10.1016/j.tox.2017.07.017. Epub 2017 Aug 1.
Contaminant involvement in the pathophysiology of obesity is widely recognized. It has been shown that low dose and chronic exposure to endocrine disruptor compounds (EDCs) potentiated diet- induced obesity. High and acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a persistent organic pollutant (POP) and an EDC with anti-estrogenic property, causes wasting syndrome . However at lower doses, the TCDD metabolic effects remain poorly understood. We investigated the obesogenic effect during chronic exposure of TCDD at 1μg/kg body weight (bw)/week in adult C57BL/6J mice fed with a high fat diet (HFD) and exposed from 10 to 42 weeks old to TCDD or equal volume of vehicle by intragastric gavage. Under these conditions, TCDD was obesogenic in adult mice (7% in males and 8% in females), which was linked to fat mass. A sex effect was observed in the fat mass distribution in adipose tissue and in the hepatic triglyceride content evolution. In visceral fat pad weight, we observed a decrease (11%) in males and an increase (14%) in females. The hepatic triglyceride content increase (41%) in females only. TCDD failed to induce any change in plasma parameters regarding glucose and lipid homeostasis. Messenger ribonucleic acid (mRNA) levels involved in adipose tissue and hepatic metabolism, inflammation, xenobiotic metabolism and endocrine disruption were differently regulated between males and females. In conclusion, these results provide new evidence that dioxin, a POP and EDC can be obesogenic for adult mice with multi-organ effects.
污染物参与肥胖的病理生理学已得到广泛认可。研究表明，低剂量长期接触内分泌干扰化合物（EDCs）会加剧饮食诱导的肥胖。高剂量急性接触2,3,7,8-四氯二苯并对二恶英（TCDD），一种持久性有机污染物（POP）和具有抗雌激素特性的EDC，会导致消瘦综合征。然而，在较低剂量下，TCDD的代谢作用仍知之甚少。我们研究了成年C57BL/6J小鼠在1μg/kg体重（bw）/周的TCDD慢性暴露下的致肥胖作用，这些小鼠喂食高脂肪饮食（HFD），从10周龄到42周龄通过胃内灌胃接触TCDD或等体积的载体。在这些条件下（1μg/kg体重（bw）/周的TCDD慢性暴露），TCDD对成年小鼠具有致肥胖作用（雄性为7%，雌性为8%），这与脂肪量有关。在脂肪组织的脂肪量分布和肝脏甘油三酯含量变化方面观察到了性别效应。在内脏脂肪垫重量方面，我们观察到雄性减少（11%），雌性增加（14%）。肝脏甘油三酯含量仅在雌性中增加（41%）。TCDD未能诱导血浆中与葡萄糖和脂质稳态相关的参数发生任何变化。参与脂肪组织和肝脏代谢、炎症、外源性物质代谢和内分泌干扰的信使核糖核酸（mRNA）水平在雄性和雌性之间受到不同的调节。总之，这些结果提供了新的证据，表明作为一种持久性有机污染物和内分泌干扰物的二恶英对成年小鼠具有致肥胖作用，并具有多器官效应。
