A metabolic constraint in de novo NAD+ synthesis drives mucosal inflammation in IBD - PubMed
4 hours ago
- #inflammation
- #metabolism
- #NAD+ synthesis
- Active IBD is characterized by increased tryptophan degradation via the JAK/STAT pathway, leading to quinolinic acid accumulation.
- The enzyme QPRT, responsible for converting quinolinic acid to NAD+, is downregulated, causing NAD+ depletion and energy deficiency.
- Knockdown of QPRT exacerbates inflammation, while supplementation with NAD+ precursors like nicotinamide riboside restores energy and reduces inflammation in models.
- The metabolic bottleneck at QPRT in NAD+ synthesis from tryptophan sustains mucosal inflammation in IBD, suggesting NAD+ restoration as a therapeutic strategy.