Fig. 4

Disturbed metabolic profile in db/db mice and the entire metabolic alteration after the empagliflozin intervention. A, B PLS-DA score showing the conspicuous differential metabolic features of the kidney (A) and serum (B) between db/m and db/db group. C, D Venn plot showing the screening methods for 264 kidney DEMs (C) and 174 serum DEMs (D) between db/m and db/db group. Metabolites with |fold change|> 1.5, VIP > 1, p < 0.05, and matched in KEGG and HMDB database, are considered as differential expressed metabolites. E KEGG pathway analysis based on the relative intensity levels of 264 kidney DEMs and 174 serum DEMs identified between db/m and db/db groups (hypergeometric test, p < 0.05; Impact > 0.1). Those enriched pathways belong to 7 types of metabolism. F Activity state of enriched metabolic pathways in db/db mice. The average intensity of all metabolites in the pathway with at least three metabolites was used to calculate the fold change of each pathway to judge the activity state of the pathway. Red, elevated activity in db/db mice; Blue, decreased activity in db/db mice. G, H 3D PLS-DA scores plot summarising the overall metabolic alteration in the kidney (G) and serum (H) among db/m, db/db, and Empa groups