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Altered hepatic metabolism in Down syndrome
Lauren N Dunn1, Brian F Niemeyer1, Neetha P Eduthan1
1Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz, Aurora, CO 80045, USA.
Cell Reports
|January 15, 2026
Summary
Down syndrome (Trisomy 21) is linked to altered liver metabolism, specifically increased bile acids and signs of liver dysfunction. Dietary fat modulation impacted these changes in a mouse model, suggesting potential therapeutic strategies.
Area of Science:
- Genetics
- Metabolomics
- Hepatology
Background:
- Down syndrome (DS), caused by Trisomy 21 (T21), is the most common human chromosomal abnormality.
- DS affects multiple organ systems, increasing risks for congenital heart defects, autoimmunity, and Alzheimer's disease.
Purpose of the Study:
- To investigate metabolic alterations in individuals with Down syndrome.
- To explore the impact of Trisomy 21 on liver metabolism and pathology using multi-omic analysis and a mouse model.
Main Methods:
- Multi-omic analysis of plasma from over 400 individuals with DS.
- Utilized a DS mouse model (Dp16) for further investigation.
- Employed bulk RNA sequencing and single-cell transcriptomics.
- Assessed the effects of dietary fat modulation.
Main Results:
- Broad metabolic changes observed in DS, characterized by elevated bile acids and liver dysfunction markers.
- Perturbed bile acid metabolism and liver pathology were conserved in the DS mouse model.
- Hepatic metabolism and inflammation were significantly impacted by Trisomy 21 in the mouse model.
- Dietary fat modulation influenced gene expression, bile acid levels, and liver pathology.
Conclusions:
- Individuals with Down syndrome exhibit altered hepatic metabolism.
- These metabolic changes, particularly in bile acid pathways, are conserved in a DS mouse model.
- Dietary interventions show potential for modulating metabolic and pathological features associated with Down syndrome.
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