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| Item Type: | Article |
|---|---|
| Title: | Autophagy acts as a brake on obesity-related fibrosis by controlling purine nucleoside signalling |
| Creators Name: | Piletic, Klara, Kayvanjoo, Amir H., Richter, Felix Clemens, Borsa, Mariana, Lechuga-Vieco, Ana V., Popp, Oliver, Grenet, Sacha, Ko, Jacky Ka Long, Luo, Lin, Zec, Kristina, Kyriazi, Maria, Haysom, Harriet K., Koneva, Lada, Sansom, Stephen, Mertins, Philipp, Powrie, Fiona, Alsaleh, Ghada and Simon, Anna Katharina |
| Abstract: | A hallmark of obesity is a pathological expansion of white adipose tissue (WAT), accompanied by marked tissue dysfunction and fibrosis. Autophagy promotes adipocyte differentiation and lipid homeostasis, but its role in obese adipocytes and adipose tissue dysfunction remains incompletely understood. Using a mouse model, we demonstrate that autophagy is a key tissue-specific regulator of WAT remodelling in diet-induced obesity. Importantly, loss of adipocyte autophagy substantially exacerbates pericellular fibrosis in visceral WAT. Change in WAT architecture correlates with increased infiltration of macrophages with tissue-reparative, fibrotic features. We uncover that autophagy restrains purine nucleoside metabolism in obese adipocytes. This ultimately leads to a reduced release of the purine catabolites xanthine and hypoxanthine. Purines signal cell-extrinsically for fibrosis by driving macrophage polarisation towards a tissue reparative phenotype. Our findings in mice reveal a role for adipocyte autophagy in regulating tissue purine nucleoside metabolism, thereby limiting obesity-associated fibrosis and maintaining the functional integrity of visceral WAT. Purine signals may serve as a critical balance checkpoint and therapeutic target in fibrotic diseases. |
| Keywords: | Adipocytes, Autophagy, Fibrosis, High-Fat Diet, Inbred C57BL Mice, Macrophages, Obesity, Purine Nucleosides, Signal Transduction, White Adipose Tissue, Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 16 |
| Number: | 1 |
| Page Range: | 9220 |
| Date: | 17 October 2025 |
| Official Publication: | https://doi.org/10.1038/s41467-025-64266-5 |
| PubMed: | View item in PubMed |
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