Growth, Development and Metabolism Programme, Singapore Institute for Clinical Sciences, Brenner Centre for Molecular Medicine, 30 Medical Drive, Singapore.
BMC Genomics. 2011 Oct 16;12:509. doi: 10.1186/1471-2164-12-509.
Although an adverse early-life environment has been linked to an increased risk of developing the metabolic syndrome, the molecular mechanisms underlying altered disease susceptibility as well as their relevance to humans are largely unknown. Importantly, emerging evidence suggests that these effects operate within the normal range of birth weights and involve mechanisms of developmental palsticity rather than pathology.
To explore this further, we utilised a non-human primate model Macaca fascicularis (Cynomolgus macaque) which shares with humans the same progressive history of the metabolic syndrome. Using microarray we compared tissues from neonates in the average birth weight (50-75th centile) to those of lower birth weight (5-25th centile) and studied the effect of different growth trajectories within the normal range on gene expression levels in the umbilical cord, neonatal liver and skeletal muscle.
We identified 1973 genes which were differentially expressed in the three tissue types between average and low birth weight animals (P < 0.05). Gene ontology analysis identified that these genes were involved in metabolic processes including cellular lipid metabolism, cellular biosynthesis, cellular macromolecule synthesis, cellular nitrogen metabolism, cellular carbohydrate metabolism, cellular catabolism, nucleotide and nucleic acid metabolism, regulation of molecular functions, biological adhesion and development.
These differences in gene expression levels between animals in the upper and lower percentiles of the normal birth weight range may point towards early life metabolic adaptations that in later life result in differences in disease risk.
尽管不良的早期生活环境与代谢综合征风险增加有关，但改变疾病易感性的分子机制及其与人类的相关性在很大程度上尚不清楚。重要的是，新出现的证据表明，这些影响在正常出生体重范围内起作用，并涉及发育可塑性的机制，而不是病理学。
为了进一步探讨这一问题，我们利用了一种非人类灵长类动物模型 Macaca fascicularis（食蟹猴），它与人类具有相同的代谢综合征的渐进史。我们使用微阵列比较了平均出生体重（50-75 百分位）新生儿和低出生体重（5-25 百分位）新生儿的组织，并研究了正常范围内不同生长轨迹对脐带、新生儿肝脏和骨骼肌中基因表达水平的影响。
我们在三种组织类型中鉴定出 1973 个在平均出生体重和低出生体重动物之间表达差异的基因（P < 0.05）。GO 分析表明，这些基因参与代谢过程，包括细胞脂质代谢、细胞生物合成、细胞大分子合成、细胞氮代谢、细胞碳水化合物代谢、细胞分解代谢、核苷酸和核酸代谢、分子功能调节、生物粘附和发育。
这些在正常出生体重范围内处于上下百分位的动物之间的基因表达水平差异可能指向生命早期的代谢适应，而在以后的生活中则导致疾病风险的差异。
