Fig. 2: HFD triggers maternal inflammation linked to behavioral deficits in male offspring.

a PCA score plot of serum proteomic data (n = 6 mice/group). b Volcano plots showing serum protein changes in HFD versus normal diet-fed mice at GD18.5. c Metascape enrichment network for HFD-altered serum protein (p < 0.05). d HFD increased lipopolysaccharide in maternal serum (normalized to mCD; n = 6 mice/group; t = 5.462, p = 0.002). e Schematic of (+)-Naloxone administration (mH-Nalo). f Volcano plot of (+)-Naloxone-altered serum proteins in HFD-fed mice. g (+)-Naloxone inhibited IL-17 signaling pathway. h (+)-Naloxone rescued social behavior deficits in male mice (n = 10 mice, 10 litters/group; sociability: oHFD: t = 0.43, p = 0.966; oH-Nalo: t = 7.562, p = 4.143e-06; social preference: oHFD: t = 0.244, p = 0.810; oH-Nalo: t = 6.620, p = 8.988e-06). i (+)-Naloxone reduced marble-burying number (n = 10 mice, 10 litters/group; t = 7.387, p = 7.513e-07). j IL-17 cytokine blockade experimental design. IL-17A blocking antibody rescued the social performance (k, n = 10 mice, 10 litters/group; sociability: t = 5.53, p = 4.43e-05; social preference: t = 3.116, p = 0.006; l, n = 10 mice, 10 litters/group; t = 3.729, p = 0.002). Data are represented as mean ± SD. In a, permutational multivariate analysis of variance (PERMANOVA) by Adonis was used to determine statistical significance (F = 3.885, p = 8.412e-06). In b and f statistical significance was assessed by a two-sided unpaired t-test, adjusted using the false discovery rate (FDR) method. In g the enrichment score was calculated, normalized to obtain the Normalized Enrichment Score (NES). Nominal P-values were computed using an empirical phenotype-based permutation test (999 permutations), with multiple comparisons corrected by FDR. In d, h, i, and k–l p-values were determined by the two-sided unpaired Student’s t-test. Source data are provided as a Source Data file. LPS Lipopolysaccharide.