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. 2023 Nov 1;55(11):2417–2432. doi: 10.1038/s12276-023-01112-y

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© The Author(s) 2023

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a Venn diagram of significantly differential metabolites in the serum and hippocampus between db/db and m/m mice (n = 6). b The alteration of the “fructose and mannose metabolism” pathway in the proteomics of db/db vs. m/m mice via GSEA (NES = 1.77, P = 0.0038) (n = 5). c Fold changes of glucose transporters in RNA-seq analysis of db/db vs. m/m mice (n = 5). Red indicates a significant increase in gene expression levels, while blue indicates significantly lower gene expression levels. d KEGG enrichment of DEGs related to significantly differential metabolites (P < 0.05) (n = 5). e Fourteen KEGG pathways involved in the classification of carbohydrate metabolism. f Based on the data from omics above, schematic representation of core metabolic and transcriptional relevant differences in the pathway of “fructose and mannose metabolism”. The circles present metabolites, and the rectangles present genes. Red indicates a significant increase in metabolite concentrations or gene expression levels, while blue indicates no detection. g–i The concentrations of sorbitol (g), fructose (h) and ATP (i) in the hippocampus of db/db and m/m mice (n = 6). j–m Representative western blot (j) and densitometric analysis of AR (k), GLUT5 (l) and KHK (m) (n = 6). The data are presented as the mean ± SEM and were analyzed by Student’s t test (g–i, k–m). *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.