Muhlhausler Beverly S, Gugusheff Jessica R, Ong Zhi Yi, Vithayathil Mini A
FOODplus Research Centre, School of Agriculture, Food and Wine, The University of Adelaide, South Australia, Australia.
Horm Mol Biol Clin Investig. 2013 Sep;15(1):25-36. doi: 10.1515/hmbci-2013-0029.
A substantial body of literature has demonstrated that the nutritional environment an individual experiences before birth or in early infancy is a key determinant of their health outcomes across the life course. This concept, the developmental origins of health and disease (DOHaD) hypothesis, was initially focused on the adverse consequences of exposure to a suboptimal nutrient supply and provided evidence that maternal undernutrition, fetal growth restriction, and low birth weight were associated with heightened risk of central adiposity, insulin resistance, and cardiovascular disease. More recently, the epidemic rise in the incidence of maternal obesity has seen the attention of the DOHaD field turn toward identifying the impact on the offspring of exposure to an excess nutrient supply in early life. The association between maternal obesity and increased risk of obesity in the offspring has been documented in human populations worldwide, and animal models have provided critical insights into the biological mechanisms that drive this relationship. This review will discuss the important roles that programming of the adipocyte and programming of the central neural networks which control appetite and reward play in the early life programming of metabolic disease by maternal overnutrition. It will also highlight the important research gaps and challenges that remain to be addressed and provide a personal perspective on where the field should be heading in the coming 5-10 years.
大量文献表明，个体在出生前或婴儿早期所经历的营养环境是其一生健康状况的关键决定因素。这一概念，即健康与疾病的发育起源（DOHaD）假说，最初关注的是暴露于次优营养供应的不良后果，并提供了证据表明母亲营养不良、胎儿生长受限和低出生体重与中心性肥胖、胰岛素抵抗和心血管疾病的风险增加有关。最近，随着母亲肥胖发生率的流行上升，DOHaD领域的注意力转向确定早期生命中暴露于过量营养供应对后代的影响。母亲肥胖与后代肥胖风险增加之间的关联已在全球人群中得到记录，动物模型为驱动这种关系的生物学机制提供了关键见解。本综述将讨论脂肪细胞编程和控制食欲及奖赏的中枢神经网络编程在母亲营养过剩导致的代谢疾病早期生命编程中所起的重要作用。它还将突出仍有待解决的重要研究空白和挑战，并就该领域在未来5至10年的发展方向提供个人观点。
