Fig. 4: Role of Nrf2 in metabolic changes during and after spaceflight.

a–d Volcano plots. The x-axis shows the log₂ fold change (FC) of plasma levels in FL-WT relative to GC-WT at L+18 (a) and R+2 (c), and FL-KO relative to GC-KO at L+18 (b) and R+2 (d). The y-axis shows the negative log₁₀ of the two-tailed test P value. Vertical dotted lines denote a linear fold change of one. Horizontal dotted lines indicate P = 0.05. e–h Numbers of increased (Inc) or decreased (Dec) metabolites in FL-WT and FL-KO mice at L+18 (e) and R+2 (f). Venn diagram of changes at L+18 (g) and R+2 (h). Altered metabolites in FL-WT/L+18 (vs. GC-WT/L+18), FL-KO/L+18 (vs. GC-KO/L+18), FL-WT/R+2 (vs. GC-WT/R+2) and FL-KO/R+2 (vs. GC-KO/R+2) were determined based on an adjusted P < 0.05. i–m Representative metabolites that were regulated by Nrf2 during spaceflight. Three metabolites with significantly increased levels in FL-WT mice at L+18 that were abrogated in FL-KO mice at L+18 were LysoPC a C18:1 (i), PC aa C34:1 (j) and SM C24:0 (k). One metabolite with a significantly increased level in FL-WT mice at R+2 that was abrogated in FL-KO mice at R+2 was CE(20:4) (l), and another metabolite with a significantly decreased level in FL-WT mice at R+2 that was abrogated in FL-KO mice at R+2 was probetaine (m). The results are presented as the mean plasma concentrations (μmol/L) ± SD. Statistical analyses were performed using a t-test adjusted using the Holm method. *Adjusted P < 0.05, **adjusted P < 0.01 and ***adjusted P < 0.001.