Figure 3. Specific depletion in inflammatory macrophages derived from scAT-LSK improves glucose metabolism in HFD mice.
(a) Schematic representation of experimental procedure: lethally irradiated CD45.1+ recipient mice were co-injected with sorted scAT-LSK and total BM cells isolated respectively from CD45.2+ CD11c-DTR and CD45.1+ donor mice, and were then fed a high fat diet (HFD) for 12 weeks, before treatment with diphtheria toxin (DT) for 1 week. (b) Body weight and (c) scAT weight of chimeric mice measured at the end of the DT treatment. (d, e) Representative histograms of CD45.2 expression in the scAT and the BM of chimeric mice. (f–h) Representative histogram (f) and quantification of the numbers of inflammatory ATM derived from scAT-LSK (g) or BM (h) identified as CD45.2+ or CD45.1+ F4/80+/MHCII+/CD11c+ cells respectively in HFD untreated (grey histogram) and DT-treated (white histogram) mice. (i) Expression of genes encoding for inflammatory cytokines analyzed by qRT-PCR in the scAT and expressed as a percent of control values obtained in untreated mice (dotted line). (j, k) Quantification of dendritic cells (F4/80-/CD11c+/MHCII+) derived from scAT-LSK (j) or the BM (k). Metabolic phenotype determined with (l) GTT and AUC and (m) insulin levels. Results are expressed in mean ± sem of 4 to 8 individual animals in HFD untreated (grey symbols) or DT treated (white symbols) groups. *p<0.05; **p<0.01, nonparametric Mann-Whitney test.