| Autor: |
Yuyao Tian, Sofie Lautrup, Patrick Wai Nok Law, Ngoc-Duy Dinh, Evandro Fei Fang, Wai-Yee Chan |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Cell & Bioscience, Vol 14, Iss 1, Pp 1-19 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2045-3701 |
| DOI: |
10.1186/s13578-023-01183-4 |
| Popis: |
Abstract Background Metabolic dysfunction is one of the main symptoms of Werner syndrome (WS); however, the underlying mechanisms remain unclear. Here, we report that loss of WRN accelerates adipogenesis at an early stage both in vitro (stem cells) and in vivo (zebrafish). Moreover, WRN depletion causes a transient upregulation of late-stage of adipocyte-specific genes at an early stage. Methods In an in vivo study, we generated wrn −/− mutant zebrafish and performed histological stain and Oil Red O staining to assess the fat metabolism. In an in vitro study, we used RNA-seq and ATAC-seq to profile the transcriptional features and chromatin accessibility in WRN depleted adipocytes. Moreover, we performed ChIP-seq to further study the regulatory mechanisms of metabolic dysfunction in WS. Results Our findings show that mechanistically WRN deficiency causes SMARCA5 upregulation. SMARCA5 is crucial in chromatin remodeling and gene regulation. Additionally, rescuing WRN could normalize SMARCA5 expression and adipocyte differentiation. Moreover, we find that nicotinamide riboside (NR) supplementation restores adipocyte metabolism in both stem cells and zebrafish models. Conclusions Our findings unravel a new mechanism for the influence of WRN in the early stage of adipogenesis and provide a possible treatment for metabolic dysfunction in WS. These data provide promising insights into potential therapeutics for ageing and ageing-related diseases. |
| Databáze: |
Directory of Open Access Journals |
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