Metabolomics signature associated with circulating serum selenoprotein P levels

Metabolomics signature associated with circulating serum selenoprotein P levels
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DOI:
10.1007/s12020-018-1816-9
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发表时间:
2019-06-01
期刊:
影响因子:
3.7
通讯作者:
Lieb, Wolfgang
Lieb, Wolfgang
中科院分区:
医学3区
文献类型:
--
作者:
di Giuseppe, Romina;Koch, Manja;Lieb, Wolfgang

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硒蛋白P(SELENOP)以前已与各种代谢性状的部分相互矛盾的结果。使用非靶向代谢组学方法鉴定SELENOP相关代谢物,可能为解开SELENOP在人类健康中的作用提供新的生物学见解。在这项横断面研究中,通过将获得的LC-MS/MS光谱与Metabolon光谱库中存储的光谱进行比较,鉴定了572种血清代谢物。使用ELISA试剂盒测量832名男性和女性的血清SELENOP水平。在考虑代谢组学数据中独立维度的数量后,循环中的SELENOP水平与572种代谢物中的24种相关,包括与丙氨酸、谷氨酸、亮氨酸、异亮氨酸和缬氨酸、未知化合物X-12063、尿酸盐和肽γ-谷氨酰-亮氨酸和N-乙酰肌肽的负相关。在SELENOP和几种脂质化合物之间观察到正相关。在已鉴定的代谢物中,支链氨基酸的每个标准差增加(异亮氨酸、亮氨酸、缬氨酸)、丙氨酸和γ-谷氨酰-亮氨酸与T2 DM的高风险相关[OR(95%CI):1.96(1.41-2.73); 1.62(1.15-2.28); 1.94(1.45-2.60)、1.57(1.17-2.11)和1.52(1.13-2.05)]。更高的血清硒代磷酸盐水平与总体健康的代谢组学特征相关,这可能为硒代磷酸盐相关代谢紊乱的潜在机制提供进一步的见解。
Selenoprotein P (SELENOP) has been previously related to various metabolic traits with partially conflicting results. The identification of SELENOP-associated metabolites, using an untargeted metabolomics approach, may provide novel biological insights relevant to disentangle the role of SELENOP in human health.In this cross-sectional study, 572 serum metabolites were identified by comparing the obtained LC-MS/MS spectra with spectra stored in Metabolon's spectra library. Serum SELENOP levels were measured in 832 men and women using an ELISA kit.Circulating SELENOP levels were associated with 24 out of 572 metabolites after accounting for the number of independent dimensions in the metabolomics data, including inverse associations with alanine, glutamate, leucine, isoleucine and valine, an unknown compound X-12063, urate and the peptides gamma-glutamyl-leucine, and N-acetylcarnosine. Positive associations were observed between SELENOP and several lipid compounds. Of the identified metabolites, each standard deviation increase in the branched-chain amino acids (isoleucine, leucine, valine), alanine and gamma-glutamyl-leucine was related to higher odds of having T2DM [OR (95% CI): 1.96 (1.41-2.73); 1.62 (1.15-2.28); 1.94 (1.45-2.60), 1.57 (1.17-2.11), and 1.52 (1.13-2.05), respectively].Higher serum SELENOP levels were associated with an overall healthy metabolomics profile, which may provide further insights into potential mechanisms of SELENOP-associated metabolic disorders.