Macrophage inhibition in the alleviation of nonalcoholic steatohepatitis caused by bariatric surgery

Figures

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  Fig. 1. Study workflow. DEGs differentially expressed genes, DEMRGs differentially expressed M1 macrophage-related genes, MRGs macrophage-related genes, NASH nonalcoholic steatohepatitis.

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  Fig. 2. scRNA-seq data of NASH and normal mouse liver tissues. A t-SNE visualization of liver cell clusters based on 33110 single-cell transcriptomes. Cell counts for endothelial cells (Endo), macrophages, T cells, B cells, DCs, cholangiocytes (Chol), hepatocytes (Hep), dividing cells, plasma B cells, and HSCs are indicated in parentheses. B Violin plots showing representative marker gene expression for each cluster. C Comparison of the proportions of cell clusters in NASH and normal tissues.

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  Fig. 3. Comparison of the DEGs between NASH cells and normal macrophages. A Volcano plot of the DEGs. B Probability density plot of fold difference of up-or down-regulated genes. C GO analysis of the DEGs. D KEGG analysis of the DEGs.

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  Fig. 4. Landscape of immunocyte infiltration in liver tissues. A The proportion of macrophages in each sample. B Comparison of immune cells between NASH and normal liver tissues.

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  Fig. 5. Landscape of immunocyte infiltration in liver tissues. A, B The proportions of immune cells in each sample and comparisons between the lifestyle intervention and control groups in the GSE106737 cohort. C, D The proportion of immune cells in each sample and comparisons between the bariatric surgery and control groups in the GSE106737 cohort. E, F The proportions of immune cells in each sample and comparisons between the lifestyle intervention and control groups in the GSE83452 cohort. G, H The proportion of immune cells in each sample and comparisons between the bariatric surgery and control groups in the GSE83452 cohort.

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  Fig. 6. Identification of M1 macrophage-related genes (MRGs). A Correlation maps of the top 10 genes associated with M1 macrophage infiltration. B Co-expression network diagram of MRGs. C Heatmap of the correlations between the M1 macrophage proportion and MRGs. D GO analysis of the MRGs. E KEGG analysis of the MRGs.

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  Fig. 7. Identification of differentially expressed M1 macrophage-related genes (DEMRGs). A Volcano plot of the DEGs between pre- and post-bariatric surgery. B Venn diagram showing the DEMRGs that overlap between DEGs and MRGs. C Heatmap of the DEMRGs before and after bariatric surgery. D Boxplots of the DEMRGs before and after bariatric surgery.

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  Fig. 8. Connectivity map (CMap) analysis results. A The significant perturbation genes with the lowest CMap connectivity score; (B) the top 10 perturbed compounds; (C) 3D chemical structures of damnacanthal, BRD-K13872703, alpha-estradiol and verapamil. (Red represents oxygen atoms, yellow represents sulfur atoms, blue represents nitrogen atoms, gray represents carbon atoms and white represents hydrogen atoms).

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  Fig. 9. Animal experiments verified that BS alleviated NASH by reducing the infiltration of M1 macrophages. A Flow chart of the construction of the NASH and sleeve gastrectomy mouse model. B Masson staining of mouse liver tissue. Scale bar: 50 μm or 20 μm. C H&E staining and oil red O staining of mouse liver tissue. Scale bar: 200 μm. D Serum ALT and AST levels. E Relative mRNA expression levels of M1 macrophages markers and M2 macrophages markers. F Relative mRNA expression levels of DEMRGs. G Elisa results of FAT1 and CXCL10 in HFD mice and SG mice.

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  Fig. 10. Animal model describes BS may alleviate NASH by downregulating M1 macrophages. Schematic representation of bariatric surgery, illustrating the removal of a portion of the stomach. Molecular characterization of proinflammatory M1 macrophages, highlighting upregulated markers associated with tissue damage.The model suggests that bariatric surgery reduces NASH progression by suppressing M1 macrophage activation.