Fig. 1: Obesity dysregulates autophagy, which limits pericellular fibrosis in WAT.
From: Autophagy acts as a brake on obesity-related fibrosis by controlling purine nucleoside signalling
A UMAP projection of human white adipocytes from lean (BMI < 30; 12822 adipocytes) and obese (BMI > 40; 9191 adipocytes) subjects. Single-nucleus RNA-seq data has been obtained from a deposited dataset (GSE176171). B Enrichment GO analysis of differentially regulated pathways in human adipocytes isolated from obese compared to lean WAT. Data analysis was conducted using the Seurat package v5.0.1. The number of genes identified for each term is labelled. C WT mice were fed a normal chow diet (NCD) or high-fat diet (HFD) for 10, 30 or 60 weeks before autophagy flux in gonadal white adipose tissue (gWAT) was assessed as explained in Materials and Methods. Western blot analysis of autophagy flux was calculated as (LC3-II (Inh) – LC3-II (Veh)). n = 3 (NCD-16), 5 (HFD-60), 6 (HFD-16), 7 (HFD10, HFD30), 8 (NCD-10, HFD-10) and 9 (NCD-30, NCD-60) mice. arb. = arbitrary D Photograph of gWAT fat pads of WT and Atg7Ad mice fed with high-fat diet (HFD) for 16 weeks. E Picrosirius red staining (PSR), specifically staining collagen I and III, of gWAT depots harvested from HFD-fed WT and Atg7Ad mice after 6, 9 and 16 weeks of feeding. Representative images are shown. Scale bar, 200 µm. F Quantification of picrosirius red positive area as a percentage of total area from (E). n = 8 (WT-6), 10 (WT-9, Atg7Ad-6, Atg7Ad-9), 12 (WT-16) and13 (Atg7Ad-16) mice. G Relative mRNA levels of ECM-related genes in gWAT after 16 weeks of HFD measured by qRT-PCR. n = 4 mice. Data are presented as mean ± SEM (C) or mean ± SD (F, G). Dots represent individual biological replicates. Data are representative (D, G) or merged from 3 independent experiments (C, F). Statistical analysis by two-way ANOVA with Tukey multi comparisons (C) or Fisher (F) test or multiple unpaired t-test (G).
