Fig. 3: Distinct metabolomic signatures in atherosclerotic mice complicated with diabetes. | Nature Communications

Fig. 3: Distinct metabolomic signatures in atherosclerotic mice complicated with diabetes.

From: Palmitic acid in type 2 diabetes mellitus promotes atherosclerotic plaque vulnerability via macrophage Dll4 signaling

Fig. 3

8-week-old male C57BL/9 background ApoE-/- mice and ApoE-/- mice received STZ injections were fed with HFD for 20 weeks. A A flowchart of establishing mouse models for atherosclerosis (AS) and atherosclerosis complicated with diabetes (AS + DM). Oil Red O (ORO) staining of aortic root plaques (B) and aorta (C) in AS and AS + DM mice. Scale bars: 400 μm (B), 1 cm (C). Quantitation of plaque area in AS and AS + DM mice expressed as the ratio of ORO-positive area to the intra-external elastic membrane (EEM) area (D, n = 6 mice, data presented as mean ± SD, ***P < 0.001)), and ORO-positive area to total aortic area (E, n = 6 mice, data presented as mean ± sd, ***P < 0.001). F Orthogonal partial least squares discriminant analysis (OPLS-DA) scatter plot illustrating the distinct metabolomic profiles between AS (blue) and AS + DM (orange) mice serum samples in the combined model (COMB). The axes denote the contributions of individual samples to the first two principal components (PC1 and PC2). G Cross-validation plot of the OPLS-DA model, corroborated by 200 permutations. The intercepts of R2 = (0.0, 0.996) and Q2 = (0.0, 0.889) confirm the model’s robustness and lack of overfitting. H A volcano plot delineating the pairwise comparisons of metabolites in AS + DM relative to AS mice. The vertical dashed lines depict the twofold abundance difference threshold, and the horizontal dashed line marks the P = 0.05 significance threshold. Metabolites exhibiting significant alterations are highlighted in orange (up-regulated) or green (down-regulated). I Top 30 significantly changed metabolites by log2 fold change. J A Venn diagram visualizing unique and shared metabolites of AS + DM and AS mice. K Metabolite annotations are performed using the Lipid Maps database, with text on either side signifying classes or categories. Illustration of the frequency of significantly altered metabolites within each category (L) and class (M) under the “Fatty Acyls” category as annotated by Lipid Maps. N Display of all significantly altered metabolites within the “fatty acids and conjugates” class based on the significance of their log2 fold change. Source data are provided as a Source Data file.

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