Gluckman P D, Hanson M A
Liggins Institute, The University of Auckland, Auckland, New Zealand.
Int J Obes (Lond). 2008 Dec;32 Suppl 7:S62-71. doi: 10.1038/ijo.2008.240.
Although variation in individual lifestyle and genotype are important factors in explaining individual variation in the risk of developing obesity in an obesogenic environment, there is growing evidence that developmentally plastic processes also contribute. These effects are mediated at least in part through epigenetic processes. These developmental pathways do not directly cause obesity but rather alter the risk of an individual developing obesity later in life. At least two classes of developmental pathway are involved. The mismatch pathway involves the evolved adaptive responses of the developing organism to anticipated future adverse environments, which have maladaptive consequences if the environment is mismatched to that predicted. This pathway can be cued by prenatal undernutrition or stresses that lead the organism to forecast an adverse future environment and change its developmental trajectory accordingly. As a result, individuals develop with central and peripheral changes that increase their sensitivity to an obesogenic environment. It provides a model for how obesity emerges in populations in rapid transition, but also operates in developed countries. There is growing experimental evidence that this pathway can be manipulated by, for example, postnatal leptin exposure. Secondly, maternal diabetes, maternal obesity and infant overfeeding are associated with a greater risk of later obesity. Early life offers a potential point for preventative intervention.
尽管在致胖环境中，个体生活方式和基因型的差异是解释个体肥胖风险差异的重要因素，但越来越多的证据表明，发育可塑性过程也起了作用。这些影响至少部分是通过表观遗传过程介导的。这些发育途径不会直接导致肥胖，而是会改变个体在晚年患肥胖症的风险。至少涉及两类发育途径。错配途径涉及发育中的生物体对预期未来不利环境的进化适应性反应，如果环境与预测的不匹配，就会产生适应不良的后果。这条途径可以由产前营养不良或压力引发，这些因素会导致生物体预测未来环境不利，并相应地改变其发育轨迹。结果，个体发育时会出现中枢和外周的变化，从而增加其对致胖环境的敏感性。它为肥胖在快速转型人群中如何出现提供了一个模型，但在发达国家也同样适用。越来越多的实验证据表明，这条途径可以通过例如产后接触瘦素等方式进行调控。其次，母亲患糖尿病、母亲肥胖和婴儿过度喂养与日后患肥胖症的风险增加有关。生命早期提供了一个预防性干预的潜在切入点。
