Janesick Amanda S, Shioda Toshihiro, Blumberg Bruce
Department of Developmental and Cell Biology, University of California, 2011 Biological Sciences 3, Irvine, CA 92697-2300, United States.
Center for Cancer Research, Massachusetts General Hospital, Bldg 149, 13th Street, Charlestown, MA 02129, United States.
Mol Cell Endocrinol. 2014 Dec;398(1-2):31-5. doi: 10.1016/j.mce.2014.09.002. Epub 2014 Sep 16.
Obesity and metabolic syndrome diseases have exploded into an epidemic of global proportions. The generally accepted cause of obesity is overconsumption of calorie-dense food and diminished physical activity (the calories in-calories out model). However, emerging evidence demonstrates that environmental factors can predispose exposed individuals to gain weight, irrespective of diet and exercise. The environmental obesogen model proposes that chemical exposure during critical stages in development can influence subsequent adipogenesis, lipid balance and obesity. Obesogens are chemicals that inappropriately stimulate adipogenesis and fat storage. Numerous obesogens have been identified in recent years and some of these have been shown to act through the peroxisome proliferator activated receptor gamma, the master regulator of adipogenesis. Others act through as yet unidentified pathways. Notably, some of these obesogens elicit transgenerational effects on a variety of health endpoints, including obesity in offspring after exposure of pregnant F0 females. Thus, prenatal exposure to xenobiotic compounds can have lasting, potentially permanent effects on the offspring of exposed animals. Transgenerational effects of chemical exposure raise the stakes in the debate about whether and how endocrine disrupting chemicals should be regulated.
肥胖和代谢综合征疾病已演变成一场全球范围的流行病。肥胖公认的原因是高热量食物摄入过多和体力活动减少(热量摄入-热量消耗模型)。然而,新出现的证据表明,环境因素可使接触者易患肥胖症,而不论其饮食和运动情况如何。环境致肥胖物模型提出,发育关键阶段的化学物质暴露可影响随后的脂肪生成、脂质平衡和肥胖。致肥胖物是不恰当地刺激脂肪生成和脂肪储存的化学物质。近年来已鉴定出多种致肥胖物,其中一些已被证明通过过氧化物酶体增殖物激活受体γ发挥作用,而过氧化物酶体增殖物激活受体γ是脂肪生成的主要调节因子。其他致肥胖物则通过尚未明确的途径发挥作用。值得注意的是,其中一些致肥胖物会对多种健康终点产生跨代效应,包括怀孕的F0雌性动物接触后其后代出现肥胖。因此,产前接触外源性化合物可对接触动物的后代产生持久、可能是永久性的影响。化学物质暴露的跨代效应增加了关于是否以及如何监管内分泌干扰化学物质这场辩论的风险。