Martin-Gronert Malgorzata S, Ozanne Susan E
University of Cambridge Metabolic Research Laboratories, Cambridge, UK.
Med Wieku Rozwoj. 2013 Jan-Mar;17(1):7-12.
As the prevalence of obesity increases across the globe, vast efforts are being directed towards understanding the origins of obesity and mechanisms underlying this rapid increase. It is well known that the current environment of an individual can affect body weight, however, growing evidence suggests that the environment in very early life may be particularly important in determining long term obesity risk. This was prompted by a series of epidemiological studies demonstrating a relationship between suboptimal early growth and later risk of obesity. Evidence from human studies as well as animal models have shown that alterations in nutrition and growth in utero and during early postnatal life can have permanent effects on systems mediating regulation of energy balance. Rapid postnatal growth in particular has been associated with increased risk of developing obesity while slower postnatal growth lowers this risk. Alterations in pathways mediating energy homeostasis have been associated with both patterns of early growth. These include changes in structure and function of neuronal pathways in the brain which lead to deregulation of pathways mediating energy balance. In addition to the alterations at the central level, early nutrition can have detrimental long-lasting effects on peripheral physiological systems, for example the storage of fat and utilization of nutrients that make an individual more prone to development of obesity. The fundamental mechanisms underlying these programmed changes are still to be fully defined, although epigenetic mechanisms may play an important role.
随着全球肥胖患病率的上升，人们正投入大量精力来了解肥胖的根源以及这一快速增长背后的机制。众所周知，个体当前的环境会影响体重，然而，越来越多的证据表明，生命早期的环境在决定长期肥胖风险方面可能尤为重要。这是由一系列流行病学研究引发的，这些研究表明早期生长欠佳与后期肥胖风险之间存在关联。来自人体研究以及动物模型的证据表明，子宫内和出生后早期的营养与生长变化会对调节能量平衡的系统产生永久性影响。尤其是出生后快速生长与肥胖发生风险增加有关，而出生后生长较慢则会降低这种风险。介导能量稳态的通路改变与这两种早期生长模式均有关联。这些改变包括大脑中神经通路的结构和功能变化，进而导致调节能量平衡的通路失调。除了中枢层面的改变，早期营养会对周围生理系统产生有害的长期影响，例如脂肪储存和营养物质利用，这会使个体更易患肥胖症。尽管表观遗传机制可能发挥重要作用，但这些程序化变化背后的基本机制仍有待全面确定。
