Fig. 2: Autophagy controls adipocyte purine nucleoside metabolism.
From: Autophagy acts as a brake on obesity-related fibrosis by controlling purine nucleoside signalling
A–C Hierarchical clustering of proteomics profiles of enriched proteins in adipocytes isolated from gWAT of WT and Atg7Ad mice fed with HFD for 16 weeks (1886 proteins identified with adjusted p-value ≤ 0.01). Colour-coding represents the log2 fold difference between WT and Atg7Ad mice (A). Enrichment GO analysis of differentially regulated pathways based on upregulated (B) or downregulated (C) proteins in adipocytes isolated from Atg7Ad compared to WT gWAT. The number of genes identified for each term is labelled. n = 4 mice. D Z-score heatmap of significantly (p < 0.05) abundant nucleotide and nucleoside metabolites in adipocytes. Metabolomics analysis was performed on adipocytes isolated from gWAT of WT and Atg7Ad mice following HFD feeding for 16 weeks. n = 3 mice. E Log2 fold change heatmap of significantly differentially abundant proteins between WT and Atg7Ad involved in pentose phosphate pathway (PPP) and purine nucleoside metabolism in adipocytes as measured by proteomics analysis (as in A). F Schematic summary of adipocyte proteome and metabolome changes upon loss of autophagy depicting simplified pentose phosphate and purine nucleoside metabolic pathways. Representative enzymes and metabolic products are colour-coded based on the fold change. G Pie chart representation of metabolic pathways identified in the enrichment GO analysis of differentially regulated pathways in human adipocyte snRNA-seq isolated from obese compared to lean WAT. H Differentially regulated GO biological pathways related to purine nucleoside metabolism in human adipocytes isolated from obese and lean subjects. The number of genes identified for each term is labelled. I, J Concentration of intracellular ATP (I) and xanthine and hypoxanthine (J) in gWAT adipocytes from WT and Atg7Ad mice fed with HFD for 16 weeks. n = 5 (I) and 11 (J) mice. Data are presented as mean ± SD. Dots represent individual biological replicates. Data are representative (I) or merged from 3 independent experiments (J). All heatmap values were scaled by row (protein/metabolite) using z-score. Statistical data analysis performed using the limma (v3.54.1) and clusterProfiler (v4.6.0) packages (A–C, E), one-way ANOVA (D), Seurat package v5.0.1 (H), unpaired t-test (I) or Mann–Whitney test (J).
