The Transcriptomic Landscape of Age-Induced Changes in Human Visceral Fat and the Predicted Omentum-Liver Connectome in Males

Figures

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  Figure 1. Heatmap of the mean expression of differentially expressed genes (DEGs) in at least one age group of both men and women. These genes were clustered for k-means = 11, and only clusters that formed gradients were displayed. The figure shows which genes become more expressed with age (cluster I) and less expressed with age (clusters A, B, and C). The functional enrichment of clusters A, B, and C indicates an overall decrease in genes involved in lipid metabolism, adipocyte differentiation, and energy expenditure processes, while the expression of genes involved in inflammatory and type I diabetes mellitus pathways increases. These genes are differentially expressed in at least one age group compared to the youngest group used as a reference. Row values are normalized by Z–score, so minimum and maximum values are row relative.

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  Figure 2. Cellular deconvolution analysis. Mean cell signature scores of each age range were calculated using XCell, which estimates cell-type populations based on transcriptomics data. Arrows indicate significance (p < 0.05) for trends with aging according to the one–way ANOVA test. Adipocyte, preadipocyte, monocyte, natural killer cell (NKT), and neutrophil populations decrease with age in males, while fibroblast and some lymphocyte populations increase. These patterns were similar in females but were not significant. Row values are normalized by Z-score, so minimum and maximum values are row relative and reflected by color. Absolute nonrelative values are reflected by square size.

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  Figure 3. Fold change and false discovery rate of genes corresponding to the senescence-associated secretory phenotype (SASP). Genes marked with * have FDR < 0.05 for limma differential expression in at least one age group. This was obtained with differential expression analysis, using the youngest group as a reference. This figure is a general overview of the profile of SASP, including those genes that were not found to be differentially expressed.

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  Figure 4. Predicted connectome between visceral fat (a) and the liver (b) in males, including predicted visceral fat secreted ligands and their experimentally demonstrated liver receptors. Bar graph demonstrating enrichment scores from the Kyoto Encyclopedia of Genes and Genomes (c), as provided by Enrichr [28], revealed aging- and metabolic disease-related pathways (c). Only genes that are part of the “Longevity regulating”, “Cholesterol metabolism”, and “AMPK signaling” pathways are highlighted in green and yellow, respectively. Other genes appear in multiple other pathways and are displayed in grey without highlighting. Row values are normalized by Z-score, so minimum and maximum values are row relative. The geometric mean of all samples of transcripts per million (TPM) is displayed to reflect the absolute nonrelative expression of the gene in the tissue compared with other genes.