Purpose: 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.
Methods: 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.
Results: 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].
Conclusions: 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.
Keywords: Hepatokine; Metabolic disorders; PopGen; SELENOP; Untargeted metabolomics.