Sargis Robert M, Heindel Jerrold J, Padmanabhan Vasantha
Department of Medicine, University of Illinois at Chicago, Chicago, IL, United States.
Program on Endocrine Disruption Strategies, Commonweal, Bolinas, CA, United States.
Front Endocrinol (Lausanne). 2019 Feb 4;10:33. doi: 10.3389/fendo.2019.00033. eCollection 2019.
Metabolic disease rates have increased dramatically over the last four decades. Classic understanding of metabolic physiology has attributed these global trends to decreased physical activity and caloric excess; however, these traditional risk factors insufficiently explain the magnitude and rapidity of metabolic health deterioration. Recently, the novel contribution of environmental metabolism-disrupting chemicals (MDCs) to various metabolic diseases (including obesity, diabetes, and non-alcoholic fatty liver disease) is becoming recognized. As this burgeoning body of evidence has matured, various organic and inorganic pollutants of human and natural origin have emerged as metabolic disease risk factors based on population-level and experimental data. Recognition of these heretofore underappreciated metabolic stressors now mandates that efforts to mitigate the devastating consequences of metabolic disease include dedicated efforts to address environmental drivers of disease risk; however, there have not been adequate recommendations to reduce exposures or to mitigate the effects of exposures on disease outcomes. To address this knowledge gap and advance the clinical translation of MDC science, herein discussed are behaviors that increase exposures to MDCs, interventional studies to reduce those exposures, and small-scale clinical trials to reduce the body burden of MDCs. Also, we discuss evidence from cell-based and animal studies that provide insights into MDC mechanisms of action, the influence of modifiable dietary factors on MDC toxicity, and factors that modulate MDC transplacental carriage as well as their impact on metabolic homeostasis. A particular emphasis of this discussion is on critical developmental windows during which short-term MDC exposure can elicit long-term disruptions in metabolic health with potential inter- and transgenerational effects. While data gaps remain and further studies are needed, the current state of evidence regarding interventions to address MDC exposures illuminates approaches to address environmental drivers of metabolic disease risk. It is now incumbent on clinicians and public health agencies to incorporate this knowledge into comprehensive strategies to address the metabolic disease pandemic.
在过去的四十年里，代谢性疾病的发病率急剧上升。对代谢生理学的传统理解将这些全球趋势归因于身体活动减少和热量摄入过多；然而，这些传统风险因素不足以解释代谢健康恶化的程度和速度。最近，环境代谢干扰化学物质（MDCs）对各种代谢性疾病（包括肥胖、糖尿病和非酒精性脂肪性肝病）的新贡献正逐渐得到认可。随着这一新兴证据体系的成熟，基于人群水平和实验数据，各种源于人类和自然的有机和无机污染物已成为代谢性疾病的风险因素。认识到这些此前未得到充分重视的代谢应激源，现在要求减轻代谢性疾病破坏性后果的努力包括专门致力于解决疾病风险的环境驱动因素；然而，目前还没有关于减少接触或减轻接触对疾病结果影响的充分建议。为了填补这一知识空白并推进MDC科学的临床转化，本文讨论了增加接触MDCs的行为、减少这些接触的干预性研究以及减少MDCs身体负担的小规模临床试验。此外，我们还讨论了来自细胞和动物研究的证据，这些证据提供了对MDC作用机制的见解、可改变的饮食因素对MDC毒性的影响，以及调节MDC胎盘转运的因素及其对代谢稳态的影响。本次讨论特别强调关键的发育窗口期，在此期间，短期接触MDCs可能会引发代谢健康方面的长期干扰，并具有潜在的代内和代际影响。虽然数据差距仍然存在，还需要进一步研究，但目前关于应对MDC接触的干预措施的证据状态阐明了应对代谢性疾病风险环境驱动因素
