Institute of Environmental Health Sciences and Department of Pharmacology, Wayne State University, Detroit, MI 48202, United States.
Division of Biological Sciences, The University of Missouri, Columbia, MO 65211, United States.
Biochem Pharmacol. 2022 May;199:115014. doi: 10.1016/j.bcp.2022.115014. Epub 2022 Apr 5.
There is increasing evidence of a role for environmental contaminants in disrupting metabolic health in both humans and animals. Despite a growing need for well-understood models for evaluating adipogenic and potential obesogenic contaminants, there has been a reliance on decades-old in vitro models that have not been appropriately managed by cell line providers. There has been a quick rise in available in vitro models in the last ten years, including commercial availability of human mesenchymal stem cell and preadipocyte models; these models require more comprehensive validation but demonstrate real promise in improved translation to human metabolic health. There is also progress in developing three-dimensional and co-culture techniques that allow for the interrogation of a more physiologically relevant state. While diverse rodent models exist for evaluating putative obesogenic and/or adipogenic chemicals in a physiologically relevant context, increasing capabilities have been identified for alternative model organisms such as Drosophila, C. elegans, zebrafish, and medaka in metabolic health testing. These models have several appreciable advantages, including most notably their size, rapid development, large brood sizes, and ease of high-resolution lipid accumulation imaging throughout the organisms. They are anticipated to expand the capabilities of metabolic health research, particularly when coupled with emerging obesogen evaluation techniques as described herein.
越来越多的证据表明，环境污染物在破坏人类和动物的代谢健康方面起着重要作用。尽管人们越来越需要充分了解评估脂肪生成和潜在肥胖生成污染物的模型，但人们一直依赖于几十年前的体外模型，而这些模型并没有得到细胞系供应商的适当管理。在过去十年中，可用的体外模型迅速增加，包括商业化的人类间充质干细胞和前体脂肪细胞模型；这些模型需要更全面的验证，但在改善向人类代谢健康的转化方面显示出了真正的前景。在开发三维和共培养技术方面也取得了进展，这些技术可以研究更接近生理状态的情况。虽然存在多种用于在生理相关背景下评估潜在肥胖生成和/或脂肪生成化学物质的啮齿动物模型，但已经确定了替代模式生物（如果蝇、秀丽隐杆线虫、斑马鱼和青鳉鱼）在代谢健康测试中的越来越多的能力。这些模型具有几个明显的优势，包括它们的大小、快速发育、较大的繁殖规模以及在整个生物体中进行高分辨率脂质积累成像的容易程度。当与本文所述的新兴肥胖生成评估技术结合使用时，它们预计将扩大代谢健康研究的能力。
