Fig. 1: Sphingolipid metabolism is suppressed in EC and resistance arteries of obese mice and correlated with pro-inflammatory phenotype.

A Schematic representation of the experimental design and of the sphingolipid pathway. Male WT mice were fed with SD or HFD for 6 months (Created in BioRender. Di Lorenzo, A. (2025)). B Body weight (WT SD n = 10 mice and WT HFD n = 9 mice). C Glucose tolerance test (GTT) (WT SD n = 15 mice, WT HFD n = 9 mice). D WB analysis of NOGO-B, ORMDLs, SPTLC1 and SPTLC2 in EC FACS-sorted from heart and lung and E, F relative quantification (WT SD n = 7 mice, WT HFD n = 8 mice). β-ACTIN was used as loading control. G Heatmap of genes for the SPT complex, inflammation, and lipid transport in FACS-sorted EC from heart and lung, *indicates that the difference is significant (WT SD n = 4 mice and WT HFD n = 4 mice). LC–MS/MS quantification of H total ceramides, I specific ceramides, C16:0-dihydroceramide (dhC16:0-Cer), dihydrosphingosine (dhSph), sphingosine (Sph), sphingosine-1-phosphate (S1P), and J total and K specific sphingomyelins (SM) in FACS-sorted EC from heart and lung (WT SD n = 16 mice, WT HFD n = 18 mice). L Immunofluorescence staining for NOGO-A/B and WGA of mesenteric arteries (MA) sections. Nogo-A/B deficient MA were used as negative control. Nuclei were stained with DAPI. LC–MS/MS quantification of M total and N specific Cer, and O total and P specific SM in MA (WT SD n = 9 mice and WT HFD n = 11 mice). Data are expressed as mean ± SEM *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001. Statistical significance was determined by unpaired t-test two-tailed (B, E, F, H–K, M–P) and two-way ANOVA with Sidak multiple comparison test (C). Source data are provided as a Source Data file.