Single-cell chromatin accessibility and lipid profiling reveals SCD1-dependent metabolic shift in adipocytes induced by bariatric surgery

Fig 1. Clustering and cell type identification of cells in epididymal and inguinal adipose depots.

Fig 2. Adipose depot specific differences in cells from SHAM surgery mice. A. Adipocyte abundances in ING (light blue) and EPI (dark blue) depots of SHAM animals. Dots represent each biological replicate. (n = 3). B. Gene accessibility differences for AD2 (left) and AD4 (right) clusters comparing ING and EPI cells. Positive and negative log2-fold changes respectively indicate increased accessibility in ING and EPI depots. C. Abundances of endothelial, APC, T-cells and macrophages in ING (light blue) and EPI (dark blue) depots of SHAM animals (n = 3). D. Gene accessibility differences for APCs ING and EPI depots. Positive and negative log2-fold changes respectively indicate increased accessibility in ING and EPI depots. *p < 0.05. Two-tailed students t-test was performed for A and C.

Fig 3. Differential accessibility of peaks with transcription factor motifs in response to VSG. A. Volcano plot of differentially accessible peaks comparing VSG to SHAM ING adipocytes. The 13,449 peaks with positive fold change indicate increased accessibility in VSG; the 4,943 peaks with negative fold change indicate decreased accessibility in VSG. FDR < 0.5 and absolute Log2-Fold Change> 0.3. B. Transcription factor motif enrichment in differentially accessible peaks using the CISBP motif database. VSG (peaks with positive fold change) and SHAM (peaks with negative fold change). C. Motif sequence logos for the top enriched motifs. D. Gene ontology enrichment for biological process using the nearest genes (<100kb) to peaks with top motifs. Adjusted P.value < 0.1 for GO enrichments. E. Overlap of the top 3,000 differentially accessible peaks for VSG and SHAM ING adipocytes containing NR3C1 motifs, and glucocorticoid receptor ChIP-seq binding regions reported in Yu et al., 2010.

Fig 4. Accessibility changes in genes after VSG in inguinal mature adipocytes. A. Volcano plot of differentially accessible genes comparing VSG to SHAM ING adipocytes. Positive fold change indicates increased accessibility in VSG cells. B. Biological process gene ontology enrichment for the top 200 most significantly differentially accessible genes. C. Volcano plots of differentially accessible genes in VSG vs SHAM in each mature adipocyte cluster.

Fig 5. Reduced accessibility in Scd1 leads to less accumulation of unsaturated fatty acids. A. Experimental design of determining FAME profiles, using three samples per depot and treatment group. B. 18-carbon fatty acid profiles, and C, corresponding desaturation index. (n = 3). D. 16-carbon fatty acid profiles, and E, corresponding desaturation index. (n = 3). *p < 0.05. Two-tailed students t-test was performed for (C,D,E,F) comparing VSG to SHAM within ING or EPI adipose samples. F. Model for the contributions of VSG to metabolic health through functional accessibility changes at Scd1.