Fig. 3: HFD-induced MIA promotes the kynurenine pathway in maternal circulation.
a PCA of serum metabolic profiles (n = 6 mice/group). b WGCNA cluster dendrogram grouped serum metabolites into modules M1-16. c Correlation heatmap between metabolite modules and HFD-altered serum proteins. d Module eigengene expression across groups (n = 6 mice/group; MEblack: F 2,15 = 79.902, mCD vs mHFD: p = 2.41e-08, mHFD vs mH-Nalo: p = 3.62e-08; MEorange: F 2,15 = 5.429, mCD vs mHFD: p = 0.012, mHFD vs mH-Nalo: p = 0.058). e qMSEA identified metabolic pathways of MEblack module. f Summary of perturbed tryptophan metabolism pathways in serum (n = 6 mice/group; mCD vs mHFD: Trp, t = 5.002, p = 0.0002847077; Kyn, t = 5.569, p = 0.0001679119; 3-HK, t = 5.004, p = 0.0003999991; Kyna, t = 3.884, p = 0.003; Quin, t = 2.594, p = 0.03; Xanthurenic Acid, t = 2.994, p = 0.01; 3-HAA, t = 6.103, p = 7.704395e-05; Serotonin, t = 4.228, p = 0.002; Melatonin, t = 3.216, p = 0.009; ILA, t = 2.591, p = 0.03; Tryptophol, t = 2.611, p = 0.03; mHFD vs mH-Nalo: Trp, t = 4.511, p = 0.001; Kyn, t = 4.383, p = 0.001; 3-HK, t = 4.994, p = 0.0004063576; Quin, t = 4.517, p = 0.001; Xanthurenic Acid, t = 3.629, p = 0.005; 3-HAA, t = 4.738, p = 0.0006114107; Melatonin, t = 2.443, p = 0.03; Tryptophol, t = 4.005, p = 0.002). In d data are represented as mean ± SD. In a Adonis was used to determine statistical significance (F = 7.704, p = 5.374e-07). In c statistical significance was determined using a two-tailed unpaired Student’s t-test, with multiple comparisons corrected using the FDR method. Statistical significance in (d) was determined using a ANOVA followed by Dunnett’s multiple comparison test, and in (f) a two-tailed unpaired Student’s t-test was used. In e p-value was determined using permutation testing (999 permutations) with adjustment using FDR. Enrichment ratio = Hits / Expected. Source data are provided as a Source Data file.
