Janesick A, Blumberg B
Departments of Developmental and Cell Biology, University of California, Irvine, CA 92697-2300, USA.
Int J Androl. 2012 Jun;35(3):437-48. doi: 10.1111/j.1365-2605.2012.01247.x. Epub 2012 Feb 28.
Obesogens are chemicals that directly or indirectly lead to increased fat accumulation and obesity. Obesogens have the potential to disrupt multiple metabolic signalling pathways in the developing organism that can result in permanent changes in adult physiology. Prenatal or perinatal exposure to obesogenic endocrine disrupting chemicals has been shown to predispose an organism to store more fat from the beginning of its life. For example, excess oestrogen or cortisol exposure in the womb or during early life resulted in an increased susceptibility to obesity and metabolic syndrome later in life. This review focuses on the effects of environmental chemicals, such as the model obesogen, tributyltin (TBT), on the development of obesity. We discuss evidence linking the obesogenic effects of TBT with its ability to activate the peroxisome proliferator-activated receptor gamma and stimulate adipogenesis. We also discuss how TBT and other environmental obesogens may lead to epigenetic changes that predispose exposed individuals to subsequent weight gain and obesity. This suggests that humans, who have been exposed to obesogenic chemicals during sensitive windows of development, might be pre-programmed to store increased amounts of fat, resulting in a lifelong struggle to maintain a healthy weight and exacerbating the deleterious effects of poor diet and inadequate exercise.
致肥胖物是直接或间接导致脂肪堆积增加和肥胖的化学物质。致肥胖物有可能扰乱发育中生物体的多种代谢信号通路,从而导致成年生理机能发生永久性变化。已表明,产前或围产期接触致肥胖的内分泌干扰化学物质会使生物体从生命伊始就更易储存脂肪。例如,子宫内或生命早期接触过量雌激素或皮质醇会导致日后对肥胖和代谢综合征的易感性增加。本综述聚焦于环境化学物质,如典型致肥胖物三丁基锡(TBT),对肥胖发展的影响。我们讨论了将TBT的致肥胖作用与其激活过氧化物酶体增殖物激活受体γ及刺激脂肪生成的能力相联系的证据。我们还讨论了TBT和其他环境致肥胖物如何可能导致表观遗传变化,使接触者更易随后体重增加和肥胖。这表明,在发育的敏感窗口期接触致肥胖化学物质的人类可能会被预先设定为储存更多脂肪,导致终生为维持健康体重而挣扎,并加剧不良饮食和运动不足的有害影响。