Adults prenatally exposed to the Dutch Famine exhibit a metabolic signature associated with a broad spectrum of common diseases.
Adults prenatally exposed to the Dutch Famine exhibit a metabolic signature associated with a broad spectrum of common diseases.
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产前经历荷兰饥荒的成年人表现出与多种常见疾病相关的代谢特征。
DOI：
10.1101/2024.04.04.24305284
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Heijmans,BastiaanT
中科院分区：
文献类型：
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作者：
Taeubert,MJazmin;Kuipers,ThomasB;Zhou,Jiayi;Li,Chihua;Wang,Shuang;Wang,Tian;Tobi,ElmarW;BBMRI-NLMetabolomicsconsortium;Belsky,DanielW;Lumey,LH;Heijmans,BastiaanT
研究背景孕期暴露于饥荒与代谢性疾病风险增加有关，包括肥胖和2型糖尿病。我们使用核磁共振代谢组学方法来确定在第二次世界大战结束时荷兰饥荒期间与产前饥荒暴露生存相关的代谢变化，并随后评估它们与疾病的联系。方法从480名产前饥荒暴露的个体(平均58.8年，0.5SD)和464名对照组(平均57.9年，5.4SD)的血清中产生核磁共振代谢组学数据。我们测试了产前饥荒暴露与168个个体代谢生物标志物水平的关系，并将饥荒暴露的代谢生物标志物特征与154种常见疾病的代谢生物标志物特征进行了比较。结果产前饥荒暴露与晚年较高的支链氨基酸(Iso)亮氨酸、芳香氨基酸(酪氨酸)和葡萄糖浓度(0.2SD，p<； 3 × 10−3)相关。产前饥荒暴露的代谢标志物特征与英国生物库中发生的2型糖尿病的代谢生物标志物特征呈正相关(r= 0.77，p= 3 × 10−27)，在重新估计非糖尿病个体产前饥荒暴露的特征时也是如此(r= 0.67，p= 1 × 10−18)。值得注意的是，这种关联扩展到了115种可获得签名的常见疾病(0.3 ≤r≤ 0.9，p<； 3.2 × 10−4)。饥荒暴露的代谢特征与疾病结局之间的相关性被减弱，当饥荒暴露的代谢特征根据体重指数进行调整时。结论产前饥荒暴露与代谢生物标志物特征密切相关，该特征与多种疾病的特征非常相似，这一观察结果在一定程度上可以归因于肥胖的共同参与。
BackgroundExposure to famine in the prenatal period is associated with an increased risk of metabolic disease, including obesity and type 2 diabetes. We employed nuclear magnetic resonance (NMR) metabolomic profiling to identify the metabolic changes that are associated with survival of prenatal famine exposure during the Dutch Famine at the end of World War II and subsequently assess their link to disease.MethodsNMR metabolomics data were generated from serum in 480 individuals prenatally exposed to famine (mean 58.8 years, 0.5 SD) and 464 controls (mean 57.9 years, 5.4 SD). We tested associations of prenatal famine exposure with levels of 168 individual metabolic biomarkers and compared the metabolic biomarker signature of famine exposure with those of 154 common diseases.ResultsPrenatal famine exposure was associated with higher concentrations of branched-chain amino acids ((iso)-leucine), aromatic amino acid (tyrosine), and glucose in later life (0.2–0.3 SD,p< 3 × 10−3). The metabolic biomarker signature of prenatal famine exposure was positively correlated to that of incident type 2 diabetes from the UK Biobank (r= 0.77,p= 3 × 10−27), also when re-estimating the signature of prenatal famine exposure among individuals without diabetes (r= 0.67,p= 1 × 10−18). Remarkably, this association extended to 115 common diseases for which signatures were available (0.3 ≤r≤ 0.9,p< 3.2 × 10−4). Correlations among metabolic signatures of famine exposure and disease outcomes were attenuated when the famine signature was adjusted for body mass index.ConclusionsPrenatal famine exposure is associated with a metabolic biomarker signature that strongly resembles signatures of a diverse set of diseases, an observation that can in part be attributed to a shared involvement of obesity.