Institute of Epidemiology, Kiel University, Kiel, Germany.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Endocrine. 2019 Jun;64(3):486-495. doi: 10.1007/s12020-018-1816-9. Epub 2018 Nov 17.
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.
硒蛋白 P(SELENOP)先前与多种代谢特征有关,但结果存在部分冲突。通过非靶向代谢组学方法鉴定与 SELENOP 相关的代谢产物,可能为阐明 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 谱与 Metabolon 谱库中的谱进行比较,鉴定了 572 种血清代谢产物。使用 ELISA 试剂盒测量了 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 SELENOP 水平与 572 种代谢产物中的 24 种相关,包括与丙氨酸、谷氨酸、亮氨酸、异亮氨酸和缬氨酸、一种未知化合物 X-12063、尿酸和肽γ-谷氨酰-亮氨酸和 N-乙酰肉碱呈负相关。SELENOP 与几种脂质化合物呈正相关。在所鉴定的代谢产物中,每种支链氨基酸(异亮氨酸、亮氨酸、缬氨酸)、丙氨酸和γ-谷氨酰-亮氨酸的标准差增加与 T2DM 的发生几率更高相关[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)]。
较高的血清 SELENOP 水平与整体健康的代谢组学特征相关,这可能为阐明 SELENOP 相关代谢紊乱的潜在机制提供进一步的见解。