Department of Developmental and Cell Biology, University of California, Irvine, California.
Department of Pharmaceutical Sciences, University of California, Irvine, California.
Basic Clin Pharmacol Toxicol. 2019 Aug;125 Suppl 3(Suppl 3):44-57. doi: 10.1111/bcpt.13214. Epub 2019 Apr 10.
Obesity and associated disorders are now a global pandemic. The prevailing clinical model for obesity is overconsumption of calorie-dense food and diminished physical activity (the calories in-calories out model). However, this explanation does not account for numerous recent research findings demonstrating that a variety of environmental factors can be superimposed on diet and exercise to influence the development of obesity. The environmental obesogen model proposes that exposure to chemical obesogens during in utero and/or early life can strongly influence later predisposition to obesity. Obesogens are chemicals that inappropriately stimulate adipogenesis and fat storage, in vivo either directly or indirectly. Numerous obesogens have been identified in recent years and some of these elicit transgenerational effects on obesity as well as a variety of health end-points after exposure of pregnant F0 females. Prenatal exposure to environmental obesogens can produce lasting effects on the exposed animals and their offspring to at least the F4 generation. Recent results show that some of these transgenerational effects of obesogen exposure can be carried across the generations via alterations in chromatin structure and accessibility. That some chemicals can have permanent effects on the offspring of exposed animals suggests increased caution in the debate about whether and to what extent exposure to endocrine-disrupting chemicals and obesogens should be regulated.
肥胖及相关疾病现已成为全球性大流行病。目前,肥胖的主流临床模式是热量密集型食物摄入过量和体力活动减少(热量摄入-消耗模式)。然而,这一解释无法说明最近大量研究结果,这些研究表明,多种环境因素可以叠加在饮食和运动之上,影响肥胖的发生。环境内分泌干扰物致肥胖模型提出,在子宫内和/或生命早期接触化学内分泌干扰物会强烈影响日后肥胖的易感性。内分泌干扰物是指在体内直接或间接不当刺激脂肪生成和脂肪储存的化学物质。近年来,已鉴定出许多内分泌干扰物,其中一些在接触怀孕 F0 雌性动物后,会对肥胖以及多种健康终点产生跨代效应。产前接触环境内分泌干扰物会对暴露动物及其后代产生持久影响,至少持续到 F4 代。最近的研究结果表明,内分泌干扰物暴露的一些跨代效应可以通过染色质结构和可及性的改变在代际间传递。一些化学物质会对暴露动物的后代产生永久影响,这表明在关于是否以及在何种程度上需要对内分泌干扰物和肥胖物进行监管的争论中,应更加谨慎。