Journal: JCI Insight

Article Title: Lipidomics unveils lipid dyshomeostasis and low circulating plasmalogens as biomarkers in a monogenic mitochondrial disorder

doi: 10.1172/jci.insight.123231

Figure Lengend Snippet: (A–D) LC-QTOF–based untargeted lipidomics from livers of fed H-Lrpprc–/– mice (n = 13) and their littermate controls (n = 8). (A) Volcano plot depicting the 1,386 features obtained following MS data processing. Using a P-corr threshold of 0.05 (corresponding to an uncorrected P value of 0.015; horizontal red dotted line) and an FC >2.5 or <0.4 (vertical red dotted lines), 92 features significantly discriminated H-Lrpprc–/– mice vs. controls, of which 60 were increased (red dots) and 32 decreased (green dots). See also Supplemental Table 3 for the list of lipids identified by MS/MS with FCs and P values (unpaired Student’s t test and with Benjamini-Hochberg correction). (B–D) Dot plots of selected lipids significantly discriminating H-Lrpprc–/– mice from controls and identified by MS/MS. Each dot represents a log2-transformed signal intensity ratio for the indicated lipid (sub)classes with their acyl side chain(s): (B) 15 glycerolipids (TGs); (C) 22 glycerophospholipids: 9 PC, 9 PE, 2 phosphatidylglycerol (PG) and 2 phosphatidylserine (PS); and (D) 4 ACs.

Article Snippet: Briefly, plasma samples or pulverized liver tissues previously freeze-clamped (20 mg) were homogenized in methanol/water (80:20, v/v) spiked with deuterated standards ([ 2 H 4 ]lithocholic acid, d 4 -LCA; [ 2 H 4 ]cholic acid, d 4 -CA; [ 2 H 4 ]chenodeoxycholic acid, d 4 -CDCA; [ 2 H 4 ]deoxycholic-2,2,4,4-d 4 acid, d 4 -DCA); [ 2 H 4 ]glycodeoxycholic acid, d 4 -GDCA; [ 2 H 4 ]glycochenodeoxycholic acid, d 4 -GCDCA; and [ 2 H 4 ]glycocholic acid, d 4 -GCA) (CDN Isotopes) and then acidified with HCl (1 mM) before homogenization and centrifugation.

Techniques: Tandem Mass Spectroscopy, Transformation Assay