PUBLICATION

WRN loss accelerates abnormal adipocyte metabolism in Werner syndrome

Authors
Tian, Y., Lautrup, S., Law, P.W.N., Dinh, N.D., Fang, E.F., Chan, W.Y.
ID
ZDB-PUB-240107-1
Date
2024
Source
Cell & Bioscience   14: 77 (Journal)
Registered Authors
Keywords
Abnormal metabolism, SMARCA5, WRN, Werner syndrome
MeSH Terms
none
PubMed
38184705 Full text @ Cell Biosci.
Citation
Tian, Y., Lautrup, S., Law, P.W.N., Dinh, N.D., Fang, E.F., Chan, W.Y. (2024) WRN loss accelerates abnormal adipocyte metabolism in Werner syndrome. Cell & Bioscience. 14:77.
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
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