Department of Twin Research and Genetic Epidemiology, Kings College London, St Thomas' Hospital, London, United Kingdom.
Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
PLoS One. 2018 Mar 22;13(3):e0194316. doi: 10.1371/journal.pone.0194316. eCollection 2018.
Several studies suggest that low birthweight resulting from restricted intrauterine growth can leave a metabolic footprint which may persist into adulthood. To investigate this, we performed metabolomic profiling on 5036 female twins, aged 18-80, with weight at birth information available from the TwinsUK cohort and performed independent replication in two additional cohorts. Out of 422 compounds tested, 25 metabolites associated with birthweight in these twins, replicated in 1951 men and women from the Hertfordshire Cohort Study (HCS, aged 66) and in 2391 men and women from the North Finland Birth 1986 cohort (NFBC, aged 16). We found distinct heterogeneity between sexes and, after adjusting for multiple tests and heterogeneity, two metabolites were reproducible overall (propionylcarnitine and 3-4-hydroxyphenyllactate). Testing women only, we found other metabolites associated with lower birthweight from the meta-analysis of the three cohorts (2-hydroxy-butyric acid and γ-glutamylleucine). Higher levels of all these metabolites can be linked to insulin resistance, oxidative stress or a dysfunction of energy metabolism, suggesting that low birthweight in both twins and singletons are having an impact on these pathways in adulthood.
多项研究表明，宫内生长受限导致的低出生体重会留下代谢痕迹，这种痕迹可能会持续到成年。为了研究这一问题，我们对来自 TwinsUK 队列的 5036 名年龄在 18 至 80 岁的女性双胞胎进行了代谢组学分析，并在另外两个队列中进行了独立验证。在测试的 422 种化合物中，有 25 种代谢物与这些双胞胎的出生体重相关，在 Hertfordshire Cohort Study（HCS，年龄 66 岁）的 1951 名男性和女性以及 North Finland Birth 1986 Cohort（NFBC，年龄 16 岁）的 2391 名男性和女性中得到了复制。我们发现性别之间存在明显的异质性，经过多次测试和异质性调整后，有两种代谢物在总体上具有可重复性（丙酰肉碱和 3-4-羟基苯乳酸）。仅对女性进行测试，我们从三个队列的荟萃分析中发现了与低出生体重相关的其他代谢物（2-羟基丁酸和γ-谷氨酰亮氨酸）。所有这些代谢物水平的升高都与胰岛素抵抗、氧化应激或能量代谢功能障碍有关，这表明双胞胎和单胎的低出生体重都会对这些途径在成年期产生影响。
