Fig. 4: Maternal HFD enhances Quin production in the fetal forebrain.
a Kyn metabolism in microglia. b Confocal images and skeleton analysis of microglia labeled with Iba-1 in fetal brain. c Microglia morphologies in mCD and mHFD fetal brain (n = 30 cells from 3 mice). GSEA showing enrichment of the inflammatory response LPS pathway (d) and main fetal microglia pathway (e) (n = 3 for each group). (+)-Naloxone administration decreased the microglial density (f) n = 9 slices from 3 mice, 3 litters/group; F 2,24 = 43.474, mCD vs mHFD: p = 1.80e-08, mHFD vs mH-Nalo: p = 2.08e-07) and mRNA expression of Kynurenine-3-monooxidase (KMO) (g) n = 6 mice, 6 litters/group; F 2,15 = 59.674, mCD vs mHFD: p = 8.09e-08, mHFD vs mH-Nalo: p = 6.98e-07) in the fetal brain. The concentrations of Kyn (h) F 2,15 = 5.516, mCD vs mHFD: p = 0.187, mHFD vs mH-Nalo: p = 0.011) and Quin (i) F 2,15 = 9.394, mCD vs mHFD: p = 0.002, mHFD vs mH-Nalo: p = 0.009) in the fetal brain tissue among three groups (n = 6 mice, 6 litters/group). j qMSEA identified the metabolic pathways in the fetal brain significantly perturbed by maternal HFD (p < 0.05). Data are represented as mean ± SD. In d,e NES was calculated as described above. Statistical significance was determined using permutation testing (999 permutations), with FDR correction. In g–i data are normalized to mCD. In f–i p-values were determined by ANOVA with Dunnett’s multiple comparison test. In j, enrichment ratio was calculated as described above, and statistical significance was assessed through permutation testing (999 permutations) with FDR correction. Source data are provided as a Source Data file. KYNU Kynureninase, KMO Kynurenine 3-monooxygenase, Iba-1 Ionized calcium binding adapter molecule 1, DAPI 4’,6-Diamidino-2-phenylindole, NMDAR N-methyl-D-aspartic acid receptor, α7nAChR α7 nicotinic acetylcholine receptor, AMPAR α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor.
