# Transcriptome analysis reveals organ-specific effects of 2-deoxyglucose treatment in healthy mice

**Authors:** Ann E. Wells, John J. Wilson, Sarah E. Heuer, John D. Sears, Jian Wei, Raghav Pandey, Mauro W. Costa, Catherine C. Kaczorowski, Derry C. Roopenian, Chih-Hao Chang, Gregory W. Carter

PMC · DOI: 10.1371/journal.pone.0299595 · PLOS ONE · 2024-03-07

## TL;DR

This study shows that 2-deoxyglucose affects gene activity differently in various organs of healthy mice, mainly influencing metabolism and immune pathways.

## Contribution

The study reveals organ-specific transcriptional effects of 2DG, identifying distinct metabolic and immune pathways modulated across tissues.

## Key findings

- 2DG treatment altered mitochondrial metabolism in the heart.
- In the small intestine, 2DG affected immunological pathways.
- Six tissue-specific gene modules were identified as significantly affected by 2DG.

## Abstract

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.

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.

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.

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.

## Linked entities

- **Chemicals:** 2-deoxy-D-glucose (PubChem CID 108223), 2DG (PubChem CID 40)
- **Diseases:** cancer (MONDO:0004992), epilepsy (MONDO:0005027), systemic lupus erythematosus (MONDO:0007915), rheumatoid arthritis (MONDO:0008383), COVID-19 (MONDO:0100096)

## Full-text entities

- **Diseases:** SLE (MESH:D008180), cancer (MESH:D009369), COVID-19 (MESH:D000086382), RA (MESH:D001172), epilepsy (MESH:D004827)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC10919611/full.md

## References

67 references — full list in the complete paper: https://tomesphere.com/paper/PMC10919611/full.md

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Source: https://tomesphere.com/paper/PMC10919611