Department of Pediatric Nutrition, Armand Trousseau Hospital, Paris, France.
Ann Nutr Metab. 2011;58 Suppl 2:30-41. doi: 10.1159/000328038. Epub 2011 Aug 12.
There is now considerable evidence that a constitutional susceptibility to fat gain is necessary for children to become obese under the pressure of an obesogenic environment; this is the programming towards obesity. The role of genetics in this programming is dominant. Besides the rare monogenic recessive forms of obesity secondary to mutations in genes involved in the hypothalamic appetite control pathways, obesity linked to mutations in melanocortin 3 and 4 receptors are more frequent due to their dominant mode of transmission. Predisposition to common obesity is polygenic and involves a network of genes; nevertheless, more research is required to elucidate their exact role. Fetal and perhaps early postnatal programming is also possible. Under- and overnutrition, diabetes, and maternal smoking during pregnancy were shown to promote later obesity and may affect the central body weight regulatory system during fetal development. The role of early postnatal factors such as formula-feeding rather than breastfeeding, excess in n-6 polyunsaturated fatty acids or protein intakes, and excessive weight gain early in life is more questionable and needs further investigation. Taking into consideration that childhood obesity is a programmed disease should modify its clinical management. Childhood obesity should no longer be considered as the result of inappropriate eating habits and/or excessive inactivity in order to relieve the obese children's discrimination and their parents' guilt. Since treatment of obese children requires a substantial motivation to continuously fight against the programmed excessive drive to eat, it seems wiser to wait for children to be old enough, thus more motivated, to initiate energy restriction. Moreover, with the great majority of children being not predisposed to obesity, prevention strategies should not be addressed to the whole pediatric population but targeted to those children at risk. Improvement of knowledge on programming towards obesity is essential to develop more promising therapeutic and preventive approaches.
现在有相当多的证据表明，对于儿童来说，在肥胖环境的压力下变得肥胖，需要有一种对脂肪增加的体质易感性；这就是肥胖的编程。遗传在这种编程中起着主导作用。除了由于涉及下丘脑食欲控制途径的基因突变导致的罕见的隐性肥胖单基因形式外，由于其显性遗传方式，与黑色素皮质素 3 和 4 受体突变相关的肥胖更为常见。常见肥胖的易感性是多基因的，并涉及到一个基因网络；然而，需要更多的研究来阐明它们的确切作用。胎儿和早期产后编程也是可能的。营养不良和营养过剩、糖尿病以及孕妇在怀孕期间吸烟都被证明会促进以后的肥胖，并可能在胎儿发育过程中影响中枢体重调节系统。早期产后因素的作用，如配方奶喂养而不是母乳喂养、n-6 多不饱和脂肪酸或蛋白质摄入过多，以及生命早期体重过度增加，其作用更值得怀疑，需要进一步研究。考虑到儿童肥胖是一种编程性疾病，应该改变其临床管理。儿童肥胖不应再被视为不良饮食习惯和/或过度不活动的结果，以减轻肥胖儿童的歧视和他们父母的内疚感。由于治疗肥胖儿童需要持续对抗编程性过度进食的驱动力，因此需要大量的动力，因此等待儿童足够大，更有动力开始限制能量摄入似乎更为明智。此外，由于绝大多数儿童不易肥胖，预防策略不应针对所有儿科人群，而应针对那些有风险的儿童。提高对肥胖编程的认识对于开发更有前途的治疗和预防方法至关重要。
