Fig. 5: TM4SF19 deletion reduces HFD-induced inflammatory responses of adipose tissue. | Nature Communications

Fig. 5: TM4SF19 deletion reduces HFD-induced inflammatory responses of adipose tissue.

From: TM4SF19-mediated control of lysosomal activity in macrophages contributes to obesity-induced inflammation and metabolic dysfunction

Fig. 5

A GSEA showing enrichment in inflammatory response (NES = −1.916643, adjusted p-value = 1.556454e-03) by genes significantly contributed to all cells of GWAT of WT HFD and TM4SF19 KO HFD mice. Among the variable genes ordered according to WT HFD and TM4SF19 KO HFD group loading, genes associated with the inflammatory response were marked with a black vertical line. B Heatmap of the downregulated genes involved in the inflammatory response in all cells of TM4SF19 KO HFD compared to WT HFD mice. Expression levels were scaled across conditions. C mRNA expression levels of genes involved in the inflammatory response in GWAT of each condition (n = 6 mice). D Immunofluorescence staining of F4/80 (green) with DAPI (blue) counterstaining in paraffin sections. Scale bar = 100 μm. E–G Representative flow profiles of CD206 (M2) and CD11C(M1) (E), TREM2 and CD11C (F), and LYVE1 and CD206 (G) expression levels in cells from GWAT of WT and TM4SF19 KO mice fed NCD (n = 3 mice) or HFD (n = 6 mice) for 12 weeks. H Time lapse images from two-photon intravital imaging of CX3CR1-GFP+ macrophages (green) in WT and TM4SF19 KO mice. PDGFRA-tdTomato-reporter (red) expression visualized PDGFRA+ cells and PDGFRA+ progenitor-derived adipocytes. Scale bars = 30 µm. (three biologically independent animals per each condition, showing representative images from a total of six fields: two fields/mouse). I Representative migration plots in the 2-dimensionally projected graph from 3-dimensional intravital images, showing macrophage migration trajectories in WT (n = 43 GFP+ cells from six fields, three biologically independent animals) and TM4SF19 KO (n = 52 GFP+ cells from six fields, three biologically independent animals) PDGFRA-Cre/LSL-tdTomato/CX3CR1-GFP mice (Also See Supplementary Movie 1). J Two-photon intravital imaging of an adipocyte phagocytized by macrophages in adipose tissue. CX3CR1-GFP signals (green) and WGA-blue (red in Figure) visualized phagocytes. The images in the lower panel indicated the destructed area of an adipocyte with dashed lines and the front line of the phagocytic progress with the arrows. Scale bars = 30 µm. (Also See Supplementary Movie 2). Data are presented as mean values ± SEM. p-values were determined by the unpaired two-sided Student’s t-test (D, F, G, I) and two-way ANOVA followed by Bonferroni post hoc tests (C, E). Source data are provided as a Source Data file.

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