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. 2024 Dec 5;15:103. doi: 10.1186/s13293-024-00680-6

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 2 — Effect of HFD on serum metabolites in male and female mice. A Principal component analysis based on relative abundance values of 49 serum metabolites measured by GC-MS. Symbols represent individual samples (n = 4 per group) according to diet treatment (Chow = red, HFD = blue) and biological sex (female = circle, male = triangle). Principal component 1 (PC1) primarily differentiates between diet treatments, while PC2 primarily differentiates between sexes. B Descending list of the top nine metabolites with the greatest partial contributions to the percentage of variance contributed to PC1 and PC2. C Heatmap of metabolites significantly altered by HFD, expressed as log-scale relative abundance. Diet effects were initially screened by two-way ANOVA, and metabolites showing significance (p < 0.05) were subsequently evaluated by t-test in a sex-specific manner. Significant effects of HFD (p < 0.05) are indicated by the presence of a heatmap color, whereas white indicates p ≥ 0.05. D Serum metabolite values for metabolites shown in panel B, expressed as relative units normalized to male Chow average and log2 transformed. Boxplots represent the 25th to 75th percentiles, horizontal line indicates the median, and whiskers demonstrate maximum and minimum values. Fisher’s LSD post-hoc paired comparisons shown for p < 0.10. Two-way ANOVA values: Succinate (Sex [p = 0.125], Diet [p < 0.0001], Interaction [p = 0.0086]); 3-Hydroxybutyrate (Sex [p < 0.0001], Diet [p = 0.0001], Interaction [p = 0.24]); Phosphoric acid (Sex [p = 0.0047], Diet [p < 0.0001], Interaction [p = 0.50]); Taurine (Sex [p = 0.0053], Diet [p < 0.0001], Interaction [p = 0.024]); Myo-inositol (Sex [p = 0.24], Diet [p < 0.0001], Interaction [p = 0.48]); Pipecolic acid (Sex [p = 0.087], Diet [p = 0.0018], Interaction [p = 0.16]); Uric acid (Sex [p = 0.0417], Diet [p = 0.0002], Interaction [p = 0.0332]); Ornithine (Sex [p = 0.26], Diet [p = 0.0009], Interaction [p = 0.0026]); Glycerol (Sex [p = 0.14], Diet [p = 0.0021], Interaction [p = 0.0004]); Hydroxyproline (Sex [p < 0.0001], Diet [p < 0.0001], Interaction [p = 0.83]); Glucose (Sex [p = 0.0041], Diet [p = 0.58], Interaction [p = 0.17]); Lactose (Sex [p = 0.004], Diet [p = 0.46], Interaction [p = 0.12]); Aspartate (Sex [p = 0.0004], Diet [p = 0.004], Interaction [p = 0.54]); Proline (Sex [p = 0.06], Diet [p = 0.0143], Interaction [p = 0.15]); Serine (Sex [p = 0.0012], Diet [p = 0.0002], Interaction [p = 0.11])