Le Magueresse-Battistoni Brigitte, Labaronne Emmanuel, Vidal Hubert, Naville Danielle
Brigitte Le Magueresse-Battistoni, CarMeN Laboratory, IN SERM U1060, Faculté de Médecine Lyon-Sud, 69600 Oullins, France.
World J Biol Chem. 2017 May 26;8(2):108-119. doi: 10.4331/wjbc.v8.i2.108.
Obesity and associated metabolic disorders represent a major societal challenge in health and quality of life with large psychological consequences in addition to physical disabilities. They are also one of the leading causes of morbidity and mortality. Although, different etiologic factors including excessive food intake and reduced physical activity have been well identified, they cannot explain the kinetics of epidemic evolution of obesity and diabetes with prevalence rates reaching pandemic proportions. Interestingly, convincing data have shown that environmental pollutants, specifically those endowed with endocrine disrupting activities, could contribute to the etiology of these multifactorial metabolic disorders. Within this review, we will recapitulate characteristics of endocrine disruption. We will demonstrate that metabolic disorders could originate from endocrine disruption with a particular focus on convincing data from the literature. Eventually, we will present how handling an original mouse model of chronic exposition to a mixture of pollutants allowed demonstrating that a mixture of pollutants each at doses beyond their active dose could induce substantial deleterious effects on several metabolic end-points. This proof-of-concept study, as well as other studies on mixtures of pollutants, stresses the needs for revisiting the current threshold model used in risk assessment which does not take into account potential effects of mixtures containing pollutants at environmental doses, ., the real life exposure. Certainly, more studies are necessary to better determine the nature of the chemicals to which humans are exposed and at which level, and their health impact. As well, research studies on substitute products are essential to identify harmless molecules.
肥胖及相关代谢紊乱是健康和生活质量方面的一项重大社会挑战，除身体残疾外还会产生严重的心理后果。它们也是发病和死亡的主要原因之一。尽管包括食物摄入过多和体力活动减少在内的不同病因已得到明确，但这些因素无法解释肥胖症和糖尿病流行趋势的发展动态，其患病率已达到大流行程度。有趣的是，有确凿数据表明，环境污染物，特别是那些具有内分泌干扰活性的污染物，可能是这些多因素代谢紊乱病因的一部分。在本综述中，我们将概述内分泌干扰的特征。我们将证明代谢紊乱可能源于内分泌干扰，并特别关注文献中的确凿数据。最后，我们将介绍如何通过使用一种原始的小鼠模型来研究长期暴露于污染物混合物的情况，结果表明，每种污染物的剂量超过其活性剂量时，污染物混合物会对多个代谢终点产生重大有害影响。这项概念验证研究以及其他关于污染物混合物的研究强调，需要重新审视当前风险评估中使用的阈值模型，该模型没有考虑环境剂量下含有污染物的混合物的潜在影响，即实际生活中的暴露情况。当然，还需要更多研究来更好地确定人类接触的化学物质的性质、接触水平及其对健康的影响。此外，对替代产品的研究对于识别无害分子至关重要。
