Department of Pathology, University of Cambridge, Cambridge, England.
PLoS One. 2009 Sep 29;4(9):e7271. doi: 10.1371/journal.pone.0007271.
A link has been established between prenatal nutrition and the development of metabolic and cardiovascular diseases later in life, a process referred to as developmental programming. It has been suggested that the trajectory of development is shifted by alterations in the maternal nutritional state leading to changes in developmental plasticity, in part underpinned by epigenetic changes in gene regulation. However, to date, only candidate gene approaches have been used to assess expression and molecular changes in the offspring of maternally undernourished animals. Furthermore, most work has focused on animals at an age where the programmed phenotype is already manifest and little is known about changes in gene expression in the offspring prior to development of obesity and related metabolic disorders. Gene expression profiles of liver, retroperitoneal white adipose fat, and biceps femoris skeletal muscle tissue from young adult male rats (55 days old) in which nutritional status had been manipulated in utero by maternal undernutrition (UN) were compared to the profiles of offspring of ad libitum fed mothers serving as the control group (AD) (8 offspring/group). The expression profiles were determined using the Illumina RatRef-12 BeadChip. No significant changes in expression were identified for skeletal muscle or white adipose tissue. However, studies of liver tissue showed 249 differentially expressed genes (143 up regulated, 106 down regulated). Although the animals at day 55 have yet to develop obesity they already show biochemical abnormalities and by day 110 express a phenotype characterized by increased adiposity and altered insulin sensitivity. An analysis of pathways affected suggests that intrauterine programming of UN animals to favor fat as an energy source results in mitochondrial dysfunction which initially affects the postnatal hepatic function and subsequently, via the resultant metabolic changes in other organs leads to the evolution of a phenotype similar to that of the metabolic syndrome.
已证实产前营养与生命后期代谢和心血管疾病的发展之间存在关联，这一过程被称为发育编程。有研究表明，母体营养状态的改变会改变发育轨迹，导致发育可塑性的改变，部分原因是基因调控的表观遗传变化。然而，迄今为止，仅采用候选基因方法来评估母体营养不良动物后代的表达和分子变化。此外，大多数工作都集中在已经表现出编程表型的动物年龄上，而对于肥胖和相关代谢紊乱发生之前后代基因表达的变化知之甚少。通过母体营养不良（UN）在子宫内操纵营养状态的雄性幼鼠（55 天大）的肝脏、腹膜后白色脂肪和二头肌股骨骨骼肌组织的年轻成年雄性大鼠（55 天大）的基因表达谱与自由进食母亲的后代的表达谱进行了比较（AD）作为对照组（8 个后代/组）。使用 Illumina RatRef-12 BeadChip 确定了表达谱。骨骼肌或白色脂肪组织的表达未发生显著变化。然而，对肝脏组织的研究表明，有 249 个差异表达基因（143 个上调，106 个下调）。尽管这些动物在第 55 天还没有发展成肥胖，但它们已经表现出生化异常，到第 110 天，它们表现出一种特征，即肥胖增加和胰岛素敏感性改变。受影响途径的分析表明，UN 动物的宫内编程优先将脂肪作为能量来源，导致线粒体功能障碍，这最初会影响产后肝功能，随后通过其他器官的代谢变化导致类似于代谢综合征的表型的演变。
