N-Palmitoyl Glutamine Is a Candidate Mediator of Cardiorespiratory Fitness
Authors' conclusion
We identified a novel, lipidated amino acid, N-pal-gln, that is positively associated with VO2max, increases after regular aerobic exercise, and is inversely associated with incident mortality. N-pal-gln stimulates mitochondrial biogenesis and efficiency, demonstrating its potential role as an exercise-stimulated transducer of cardiorespiratory fitness.
Study context
- Population
- HERITAGE Family Study participants with VO2max measured by cardiopulmonary exercise testing who underwent 20 weeks of supervised endurance training; replication in FHS; mortality in JHS and MESAHERITAGE
- Participants
- 654 participants
- Outcome
- Metabolite-VO2max relationships
Methodological detailsnontargeted plasma metabolomics, replication cohort, C2C12 myotube experiments
- Nontargeted plasma metabolomics
- Replication cohort
- C2C12 myotube experiments
Main finding
As reported in the abstract
N-pal-gln and VO2max
- Unknown peak (m/z 385.3056) identified as N-palmitoyl glutamine (N-pal-gln): strongest positive relationship with VO2max (adjusted for age, sex, race, lean body mass), β
- 1.29
- False discovery rate q
- 5.3×10-6
- Replication in FHS (n=408), β
- 1.2
- Replication in FHS, P
- P=3.8×10-5
Observational data: associations, not effects.
Further findings
| Outcome | HR | P value |
|---|---|---|
| All-cause mortality by N-pal-gln levelsN-pal-gln · JHS · inverse association | 0.91 | P = 0.029 |
| All-cause mortality by N-pal-gln levelsN-pal-gln · MESA · inverse association | 0.65 | P = 0.028 |
N-pal-gln change after exercise training · 20 weeks
- Log fold change
- 0.22
- Q
- 5.3×10-12
Mitochondrial:nuclear DNA ratio vs control (C2C12 myotubes)
- Increase at 6.5 nM N-pal-gln (P=0.04)
- 15%
- Increase at 26 nM N-pal-gln (P=0.02)
- 20%
- Dose-dependent
Phosphate:oxygen ratio, N-pal-gln 26 nM, ADP 0–100 μM
- Increased; ANOVA
- P = 0.0027
Original publication
N-Palmitoyl Glutamine Is a Candidate Mediator of Cardiorespiratory Fitness. Circulation. Published 12 November 2025. doi:10.
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