Transcriptome analysis reveals organ-specific effects of 2-deoxyglucose treatment in healthy mice.
Document Type
Article
Publication Date
1-1-2024
Original Citation
Wells A,
Wilson J,
Heuer S,
Sears J,
Wei J,
Pandey R,
Costa M,
Kaczorowski C,
Roopenian DC,
Chang C,
Carter GW.
Transcriptome analysis reveals organ-specific effects of 2-deoxyglucose treatment in healthy mice. PLoS One. 2024;19(3):e0299595.
Keywords
JMG, SS1, Mice, Animals, Deoxyglucose, Mice, Inbred C57BL, Glucose, Epilepsy, Gene Expression Profiling
JAX Source
PLoS One. 2024;19(3):e0299595.
ISSN
1932-6203
PMID
38451972
DOI
https://doi.org/10.1371/journal.pone.0299595
Grant
This work was supported by NIH grant GM115518 to GWC, and The Jackson Laboratory Director’s Innovation Fund (JAX-DIF 19000-18-19) and the Longevity Impetus Grant from Norn Group to C-HC
Abstract
OBJECTIVE: Glycolytic inhibition via 2-deoxy-D-glucose (2DG) has potential therapeutic benefits for a range of diseases, including cancer, epilepsy, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), and COVID-19, but the systemic effects of 2DG on gene function across different tissues are unclear.
METHODS: This study analyzed the transcriptional profiles of nine tissues from C57BL/6J mice treated with 2DG to understand how it modulates pathways systemically. Principal component analysis (PCA), weighted gene co-network analysis (WGCNA), analysis of variance, and pathway analysis were all performed to identify modules altered by 2DG treatment.
RESULTS: PCA revealed that samples clustered predominantly by tissue, suggesting that 2DG affects each tissue uniquely. Unsupervised clustering and WGCNA revealed six distinct tissue-specific modules significantly affected by 2DG, each with unique key pathways and genes. 2DG predominantly affected mitochondrial metabolism in the heart, while in the small intestine, it affected immunological pathways.
CONCLUSIONS: These findings suggest that 2DG has a systemic impact that varies across organs, potentially affecting multiple pathways and functions. The study provides insights into the potential therapeutic benefits of 2DG across different diseases and highlights the importance of understanding its systemic effects for future research and clinical applications.