Journal: bioRxiv
Article Title: Metabolic Origins of Neurotoxic 1-deoxySphingolipids in Type 2 Diabetes
doi: 10.1101/2025.04.25.650588
Figure Lengend Snippet: a Violin plots showing skin amino acid levels in T2D (N=38) and healthy controls (N=39). Glycine (Gly), Glutamate (Glu), Arginine (Arg), Aspartate (Asp), Isoleucine (Ile), Leucine (Leu), Lysine (Lys), Methionine (Met), Phenylalanine (Phe), Proline (Pro), Threonine (Thr), Tyrosine (Tyr), Valine (Val) were measured using targeted LC-MS/MS metabolomics. Statistical significance was tested using Mann-Whitney and corrected for multiple testing using a two stages step-up method (Benjamini, Krieger and Yekutieli) b L-Alanine to L-Serine ratio (ala/ser) in skin tissue of T2D (N=38) compared to healthy controls (N=39). p reflects the significance of the group comparisons (Student’s unpaired t-test, ****=p<0.0001) c Correlation of plasma 1-deoxySL/SL and skin 1-deoxySL/SL. All correlations are represented as Pearson Correlation coefficient calculated from the whole cohort (N=77, red T2D, blue Controls). d Sphingolipidomics analysis of human plasma High density (HDL) and Low density lipoproteins (LDL). Lipoproteins were isolated from healthy donors and analyzed using untargeted LC- MS/MS lipidomics as described. e Amino acid and f Sphingolipidomics analysis of 6 and 12 weeks old, db/db (dbdb, N=10 and N=10, respectively) or db/+ (dbplus, N=10 and N=9, respectively) mouse liver tissue samples g Sphingolipidomics analysis of 6 and 12 weeks old, db/db (dbdb) or db/+ (dbplus) liver tissues and corresponding mouse plasma samples. h Correlation of liver and plasma 1-deoxySL/SL in dbdb mice. i Amino acid and j Sphingolipidomics analysis of 6 weeks old streptozotocin (STZ, N=15) or Vehicle (N=10) treated rat liver samples. k Sphingolipidomics analysis of 6 weeks old streptozotocin (STZ, N=15) or Vehicle (N=10) treated rat plasma samples. l Correlation of 1-deoxySL/SL in liver and plasma of the STZ rat vs control.
Article Snippet: List of internal standards: D5-1-desoxymethylsphinganine (m17:0, 860476, Avanti Polar Lipids) 100pmol/sample D7-Sphinganine (d18:0, 860658, Avanti Polar Lipids) 100pmol/sample D7-Sphingosine (d18:1, 860657, Avanti Polar Lipids) 100pmol/sample D7-Sphingosine-1-phosphate (d18:1, 860659, Avanti Polar Lipids) 50pmol/sample 1-deoxydihydroceramide (m18:0/12:0, 860460P, Avanti Polar Lipids) 100pmol/sample 1-deoxyceramide (m18:1/12:0, 860455, Avanti Polar Lipids) 100pmol/sample Dihydroceramide (d18:0/12:0, 860635, Avanti Polar Lipids) 100pmol/sample Ceramide (d18:1/12:0, 860512, Avanti Polar Lipids) 100pmol/sample SM (d18:1/12:0, 860583, Avanti Polar Lipids) 100pmol/sample Glucosylceramide (d18:1/8:0, 860540, Avanti Polar Lipids) 100pmol/sample SPLASH lipidomics standard (330707, Avanti Polar Lipids) 2.5µL/sample Dilutions of pooled quality control samples (QC 100%, QC 75%, QC 50%, QC 25%, QC 10%) were analysed regularly during the measurement.
Techniques: Liquid Chromatography with Mass Spectroscopy, MANN-WHITNEY, Clinical Proteomics, Isolation, Control