Breton Christophe
Unité Environnement Périnatal et Croissance, UPRES EA 4489, Université Lille-Nord de France.
Horm Mol Biol Clin Investig. 2013 Aug;14(1):33-47. doi: 10.1515/hmbci-2013-0010.
The epidemiological studies initially indicated that maternal undernutrition leading to a low birth weight may predispose to the long-lasting energy balance disorders. A high birth weight due to maternal obesity or diabetes, inappropriate early postnatal nutrition, and rapid catch-up growth, may also sensitize to an increased risk of obesity. As stated by the developmental origin of health and disease concept, the perinatal perturbation of the fetus/neonate nutrient supply might be a crucial determinant of the individual programming of the body weight set point. The adipose tissue is considered as the main fuel storage unit involved in the maintenance of the energy homeostasis. Several models have demonstrated that this tissue is a prime target of the developmental programming in a gender- and depot-specific manner. In the rodents, the perinatal period of life corresponds largely to the period of adipogenesis. In contrast, this phenomenon essentially takes place before birth in bigger mammals. Despite these different developmental time windows, the altricial and precocial species share several common offspring programming mechanisms. Thus, the adipose tissue of the offspring from malnourished dams exhibited impaired glucose uptake and leptin/insulin resistance with increased proinflammatory markers. It also displayed a modified sympathetic activity, circadian rhythm, fatty acid composition, and thermogenesis. This might lead to the reprogrammed metabolism and distribution of the adipose tissue with enhanced adipogenesis and fat accumulation predisposing to adiposity. The inappropriate glucocorticoid (GC) levels and modified tissue sensitivity might be key actors of perinatal programming and long-lasting altered adipose tissue activity in the offspring. Following maternal malnutrition, the epigenetic mechanisms might also be responsible for the adipose tissue programming.
流行病学研究最初表明，母亲营养不良导致低出生体重可能易引发长期的能量平衡紊乱。母亲肥胖或糖尿病、出生后早期营养不当以及快速追赶生长导致的高出生体重，也可能增加肥胖风险。正如健康与疾病的发育起源概念所述，胎儿/新生儿营养供应的围产期扰动可能是个体体重设定点编程的关键决定因素。脂肪组织被认为是维持能量稳态的主要燃料储存单位。多种模型已证明，该组织是以性别和储存部位特异性方式进行发育编程的主要靶点。在啮齿动物中，围产期在很大程度上对应于脂肪生成期。相比之下，在较大的哺乳动物中，这种现象主要发生在出生前。尽管存在这些不同的发育时间窗口，但晚成性和早熟性物种有几种共同的后代编程机制。因此，营养不良母鼠后代的脂肪组织表现出葡萄糖摄取受损、瘦素/胰岛素抵抗以及促炎标志物增加。它还表现出交感神经活动、昼夜节律、脂肪酸组成和产热的改变。这可能导致脂肪组织的代谢和分布重新编程，脂肪生成和脂肪堆积增加，易引发肥胖。不适当的糖皮质激素（GC）水平和改变的组织敏感性可能是围产期编程以及后代脂肪组织长期活动改变的关键因素。母亲营养不良后，表观遗传机制也可能导致脂肪组织编程。
