Fig. 8: Hepatocyte senescence correlate with multi-organ dysfunction. | Nature Communications

Fig. 8: Hepatocyte senescence correlate with multi-organ dysfunction.

From: Targeting senescent hepatocytes for treatment of metabolic dysfunction-associated steatotic liver disease and multi-organ dysfunction

Fig. 8

A Box plot showing the enrichment of SHGS+ hepatocytes in visceral adipose tissue (VAT) from lean individuals and individuals with obesity (GSE235696). SHGS enrichment is significantly higher in individuals with obesity (Lean: n = 4, obesity: n = 4). B Box plot showing SHGS enrichment in subcutaneous abdominal adipose tissue from metabolically healthy lean individuals (MHL), metabolically healthy individuals with obesity (MHO), and metabolically unhealthy individuals with obesity (MUO) (GSE244118). SHGS enrichment is highest in MUO individuals (MHO: n = 15, MHO: n = 19, MUO: n = 19). C SHGS enrichment in subcutaneous abdominal adipose tissue from MHL, MHO, and MUO individuals in a second dataset (GSE156906). The trend of higher SHGS enrichment in MUO individuals is replicated (MHO: n = 14, MHO: n = 25, MUO: n = 17). D Box plot showing SHGS enrichment in pancreatic islets from individuals with varying levels of insulin sensitivity and hyperglycemia. SHGS enrichment positively correlates with HbA1c levels (Normal: n = 51, IGT: n = 15, T2D: n = 11). E Box plot showing SHGS enrichment in failing hearts with preserved ejection fraction (HFpEF; n = 41) and failing hearts with reduced ejection fraction (HFrEF, n = 59), compared to Normal (n = 45). F Box plot showing SHGS enrichment in patients with diabetes-chronic kidney disease (D-CKD; n = 19), diabetes (n = 21), and hypertension (n = 19) (left panel). By merging Normal, diabetes, and hypertension into Control, significant SHGS enrichment in the D-CKD group persisted relative to this combined control group. G Gene Set Enrichment Analysis (GSEA) plots showing the suppression of pathways related to dilated cardiomyopathy, type 1 diabetes mellitus, and cancer in DpC-treated mice with CDAHFD-induced MASH. Boxplot shows the upper quantile (75%), median (50%), and lower quantile (25%) of overall data distribution. p-values were calculated using two-sided Wilcoxon Rank Sum test for box plots in (A, B, C, D) (left), (E, F), and Pearson’s correlation test for in (D) (right), and permutation test, then adjusted for multiple-comparison testing using the Benjamini–Hochberg method in (G).

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