Extended Data Fig. 8: Blocking ceramide synthesis improves PAQR4-induced metabolic defects.
From: PAQR4 regulates adipocyte function and systemic metabolic health by mediating ceramide levels
(a) Oil Red O staining (n = 3) and adipocyte markers (n = 4 biological samples) indicate that C2-Ceramide (C2-Cer) blocks adipogenesis in sWAT stromal vascular fraction (SVF) cells. Scale bar 200 µm. (b) C2-Cer causes de-differentiation of adipocytes with expression of fibroblast marker S100A4 and decreased expression of adipocyte markers (n = 6 biological samples). Adipocytes were treated with C2-Cer post-differentiation (PD) for the indicated days. Scale bar 100 µm. (c) Expression of adipogenic markers in SVF cells that were differentiated in the absence or presence of 5 µM C2-Cer or 10 µM myriocin (Myr) at day 4 of post-differentiation (n = 6 biological samples). (d-e) Body weight and weight gain upon Myr treatment in mice priorly fed dox-HFD for 12 weeks (n = 6). (f) H&E staining of adipose tissues and liver after 5 weeks of Myr treatment (WT, n = 3; Myr, n = 4). Scale bar 200 µm. (g) Tissue weights after 5 weeks of Myr treatment (n = 6). (h) Myr treatment reduced liver triglyceride content in Paqr4ad mice (n = 6). (i) Food intake upon Myr treatment in mice priorly fed dox-HFD for 12 weeks (n = 6). * indicates comparisons between groups of WT-Veh and WT-Myr; # indicates comparisons between groups of Paqr4ad-Veh and Paqr4ad-Myr. Data shown as mean ± SEM and analysed by two-way ANOVA followed by Holm-Sidak multiple-comparison test (a, c-e, g-i) and two-tailed unpaired t-test (b).
