Fig. 1: IRF5 expression is associated with ATM metabolic adaptation to short-term caloric excess.

a, b Wild-type (WT) mice and mice with myeloid-deficiency of IRF5 (IRF5-KO) were placed on (a) 12-week long-term (LT-) high-fat diet (HFD) or (b) 4-week short-term (ST-)HFD. F4/80+ adipose tissue macrophages (ATM) were sorted from epididymal fat pads (EpiWAT) for RNA-seq. Differentially expressed genes between genotypes were used for gene ontology analysis (n = 4 per genotype, Wald test p-value <0.05, Log2FC > 1.0). Heatmaps represent fold-enrichment (Binomial test of gene list compared to reference genome, p values in Fig. S1A, B). c Irf5 expression in EpiWAT from C57BL/6 J mice on normal chow diet (NCD), ST-HFD or LT-HFD (n = 10 per group; Kruskal–Wallis multiple comparisons, left-to-right **p = 0,0063; **p = 0,0015). d JC1-Green and JC1-Red fluorescence to assess mitochondrial mass (MT Mass) and membrane potential (mΔΨ) in ATMs of C57BL/6 J mice on NCD, ST-HFD or LT-HFD (n = 10 per group on NCD/ST-HFD; n = 7 on LT-HFD; one-way ANOVA, **p = 0.0079; ****p = 0,000094). e Oxygen consumption rate (OCR) from ATMs of C57BL/6 J mice on NCD, ST-HFD or LT-HFD. Cells treated with Oligomycin (Oli), carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) and Rotenone/Antimycin A (Rot/AA) (n = 4 on NCD, n = 9 on ST-HFD, n = 8 on LT-HFD). f Correlation between IRF5 and JC1-Green MFI (Linear regression, Pearson correlation R2 = 0.36; p = 0.02) and JC1-Red/JC1-Green MFI (R2 = 0.22; p = 0.04) in ATMs of C57BL/6 J mice on NCD or ST-HFD (n = 9 per group). g Correlation between Irf5 and F4/80 expression in EpiWAT of C57BL/6 J mice on NCD or ST-HFD (n = 10 per group). h IRF5 MFI in F4/80Lo and F4/80Hi ATMs of C57BL/6 J mice on NCD or ST-HFD (n = 10 per group, two-tailed unpaired t-test, **p = 0.004). i Flow cytometry contour plots of JC1-Green and JC1-Red in F4/80Hi ATMs of C57BL/6 J on NCD or ST-HFD. MFI of JC1-Green and JC1-Red in F4/80Hi ATMs (n = 10 mice per group, two-tailed unpaired t-tests, *p = 0.01; ***p = 0.0009). j MFI of JC1-Red and JC1-Red/JC1-Green in F4/80Hi EpiWAT ATMs of WT and IRF5-KO mice on ST-HFD (n = 10 for WT and 12 for IRF5-KO, two-tailed unpaired t-tests, **p = 0.0032; *p = 0.019). k tSNE plot of F4/80 and JC1-Red MFI on the stromal vascular fraction of EpiWAT, tSNE plot of JC1-Red MFI on F4/80Hi populations from mice on ST-HFD. Data presented as mean ± SEM. Source Data file provided.