Unité Environnement Périnatal et Croissance, UPRES EA 4489, Equipe Dénutritions Maternelles Périnatales, Université Lille-Nord de France, Villeneuve d'Ascq, France;
Am J Physiol Endocrinol Metab. 2013 Nov 15;305(10):E1195-207. doi: 10.1152/ajpendo.00231.2013. Epub 2013 Sep 17.
Epidemiological studies demonstrated initially that maternal undernutrition results in low birth weight with increased risk for long-lasting energy balance disorders. Maternal obesity and diabetes associated with high birth weight, excessive nutrition in neonates, and rapid catchup growth also increase the risk of adult-onset obesity. As stated by the Developmental Origin of Health and Disease concept, nutrient supply perturbations in the fetus or neonate result in long-term programming of individual body weight set point. Adipose tissue is a key fuel storage unit involved mainly in the maintenance of energy homeostasis. Studies in numerous animal models have demonstrated that the adipose tissue is the focus of developmental programming events in a sex- and depot-specific manner. In rodents, adipose tissue development is particularly active during the perinatal period, especially during the last week of gestation and during early postnatal life. In contrast to rodents, this process essentially takes place before birth in bigger mammals. Despite these different developmental time windows, altricial and precocial species share several mechanisms of adipose tissue programming. Offspring from malnourished dams present adipose tissue with a series of alterations: impaired glucose uptake, insulin and leptin resistance, low-grade inflammation, modified sympathetic activity with reduced noradrenergic innervations, and thermogenesis. These modifications reprogram adipose tissue metabolism by changing fat distribution and composition and by enhancing adipogenesis, predisposing the offspring to fat accumulation. Subtle adipose tissue circadian rhythm changes are also observed. Inappropriate hormone levels, modified tissue sensitivity (especially glucocorticoid system), and epigenetic mechanisms are key factors for adipose tissue programming during the perinatal period.
流行病学研究最初表明，母体营养不良会导致低出生体重，并增加长期能量平衡紊乱的风险。与高出生体重相关的母体肥胖和糖尿病、新生儿过度营养以及快速追赶生长也会增加成年后肥胖的风险。正如健康与疾病起源的发展概念所述，胎儿或新生儿的营养供应波动会导致个体体重设定点的长期编程。脂肪组织是主要参与维持能量平衡的关键燃料储存单位。大量动物模型研究表明，脂肪组织是发育编程事件的焦点，具有性别和脂肪组织特异性。在啮齿动物中，脂肪组织的发育在围产期特别活跃，特别是在妊娠的最后一周和出生后的早期。与啮齿动物不同，这个过程主要发生在较大哺乳动物出生前。尽管有这些不同的发育时间窗口，但早产儿和早成性物种共享几种脂肪组织编程机制。来自营养不良母体的后代的脂肪组织存在一系列改变：葡萄糖摄取受损、胰岛素和瘦素抵抗、低度炎症、交感神经活动减少伴去甲肾上腺素神经支配减少以及产热。这些改变通过改变脂肪分布和组成以及增强脂肪生成来重新编程脂肪组织代谢，使后代容易脂肪堆积。还观察到脂肪组织昼夜节律变化的细微变化。在围产期，激素水平不当、组织敏感性改变（尤其是糖皮质激素系统）和表观遗传机制是脂肪组织编程的关键因素。
