Figure 4
From: Deficiency of the lipid flippase ATP10A causes diet-induced dyslipidemia in female mice
Atp10A deletion leads to substantial perturbations in the plasma lipidome and visceral fat transcriptome in female mice on a HFD. (a) Lipid metabolites from fasting plasma were measured by HPLC-IM-MS/MS and the data was processed via Progenesis QI. The table indicates the number of total and significantly changed lipid metabolites (compounds) observed from each ionization mode (Negative and Positive); the volcano plot illustrates the fold changes (FC) of compounds between 10A−/− vs. 10A+/+ mice, the grey shading indicates changes that did not meet the significance criteria. P-values by ANOVA. (10A+/+ n = 8 , 10A−/− n = 8 , see Supplemental Table 3 for complete information about sample size) (b) The log2(FoldChange) of lipid metabolites compared between 10A−/− vs. 10A+/+ mice are grouped by indicated categories (green and blue indicate the % of lipid species with positive and negative fold change, respectively, between 10A−/− vs. 10A+/+ mice; P values \(\le\) 0.1 by ANOVA). (c) Sequencing of visceral fat mRNA was performed using the Illumina NovaSeq 6000. The table provides the criteria used to calculate the number of differentially expressed genes (DEGs) and how many DEGs were measured; the volcano plot illustrates the DEGs (10A+/+ n = 3,10A−/− n = 3). (d) Schematic illustrating the metabolic pathways linking ATP10A substrates to observed changes in the plasma lipidome and visceral fat transcriptome. Lipid metabolites with significant changes due to 10A deletion from panel b are in bold red, the hexosylceramide category includes both GalCer and GlcCer. The protein products from two mRNA transcripts that were significantly upregulated in the visceral fat from 10A−/− mice (panel c), Pla2G5 and Lipf, are highlighted to show their role in lipid metabolism. Schematic created using Biorender.com. See Supplemental Table 2 for RNASeq KEGG pathway analysis. PC = phosphatidylcholine, AA = arachidonic acid, TG = triglyceride, FA = fatty acids, FFA = free fatty acids, DAG = diacylglycerol, MAG = monoacylglycerol, SM = sphingomyelin, S1P = sphingosine 1-phosphate, C1P = ceramide 1-phosphate, GalCer = galactosylceramide, GlcCer = glucosylceramide.
