Extended Data Fig. 5: Lipolytic dysregulation in Lpcat3AKO mice during DIO.
From: Dietary control of peripheral adipose storage capacity through membrane lipid remodelling
(a) 14C-oleate uptake in insulin-target tissues from 13-week-old control and Lpcat3AKO mice fed HFD for 5 weeks (n = 7, 8). Radioactivity (counts per min, CPM) was calculated in the extracted lipids from whole-organs 4 h post-gavage with 14C-Triolein and normalized for g/tissue. (b) Ex vivo β-oxidation in crude lysates prepared from iWAT, iBAT, or liver lysates of 13-week-old control and Lpcat3AKO mice fed HFD for 5 weeks, as assessed by the conversion of 14C-palmitic acid (PA) to 14CO2 (n = 4, 4). (c) Ex vivo lipolysis in freshly dissected iWAT explants from 13-week-old control and Lpcat3AKO mice fed HFD for 5 weeks (n = 3, 3). Secreted glycerol was determined under basal and stimulated (2 µM isoproterenol, ISO) lipolytic states. (d) 14C-oleate uptake in insulin-target tissues from 18-week-old control and Lpcat3AKO mice fed HFD for 10 weeks (n = 9, 8). (e,f) 14C-oleate uptake and turnover in (e) iBAT and (f) livers from 18-week-old control and Lpcat3AKO mice fed HFD for 10 weeks. Radioactivity (counts per min, CPM) was calculated in extracted lipids from whole-organs 4 h (n = 9, 8); 4 days (n = 6, 6); and 20 days (n = 7, 7) post-gavage with 14C-Triolein and normalized for g/tissue. (g) UMAP projection of 28,414 sequenced iWAT nuclei or split by genotype (13,466 and 14,948 nuclei for 18-week-old control vs. Lpcat3AKO mice fed HFD for 10 weeks). (h) Violin plots (clusters as columns, genes as rows) of cluster-specific markers. (i) Heatmap of normalized expression values of pan-adipogenic markers in inguinal adipocytes and the SVC fraction. Alternatively activated macrophages (AAMs), lipid-scavenging macrophages (LSMs), adipose stem and progenitor cells (ASPCs). Data are presented as mean ± SEM. ***P < 0.001 by Welch’s t-tests with FDR correction using the Benjamini, Krieger, and Yekutieli procedure (b-d).
