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Lookup NU author(s): Dr Guy TaylorORCiD, Dr Daniel WestORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2026.Exercise orchestrates an interorgan communication network, in which skeletal muscle releases signaling molecules known as myokines that contribute to exercise training-induced adaptations. We identified the muscle-derived metabolite beta-aminoisobutyric acid (BAIBA) as a regulator of adipose and hepatic metabolic responses to exercise. Here, we demonstrate that BAIBA regulates muscle metabolism, morphology and function via peroxisome proliferator-activated receptor delta (PPARδ) to determine exercise performance in mice. BAIBA mitigates muscle dysfunction in a mouse model of diabetes. Physiologically, BAIBA exists as D- and L- enantiomers. We identify L-BAIBA as the primary mediator of muscular effects. Knockdown of L-BAIBA’s biosynthetic enzyme, 4-aminobutyrate aminotransferase, in mouse hindlimb muscle impairs exercise-induced adaptations and performance gains. L-BAIBA regulates human myotube fibertype and differentiation markers through Mas-related G-protein coupled receptor D. In humans, plasma L-BAIBA correlates with aerobic fitness and increases with endurance exercise training. BAIBA acts through the PGC1α-BAIBA-PPARδ axis to facilitate muscle adaptation and exercise performance.
Author(s): Daou HN, Watt NT, Gad SA, MacCannell ADV, Ali A, Cheng C, Fernando RL, Futers TS, Khetarpal SA, Gallagher H, Chinait LD, Moriscot AS, Knuiman P, Manusama K, Mensink M, Teh I, Schneider JE, Cubbon R, Taylor GS, West DJ, Beech DJ, Bowen TS, Roberts LD
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2026
Volume: 17
Issue: 1
Online publication date: 18/08/2026
Acceptance date: 15/07/2026
Date deposited: 01/09/2026
ISSN (electronic): 2041-1723
Publisher: Nature Research
URL: https://doi.org/10.1038/s41467-026-76307-8
DOI: 10.1038/s41467-026-76307-8
Data Access Statement: RNA-Seq data associated with this study are available from EBI ArrayExpress repository (https://www.ebi.ac.uk/biostudies/arrayexpress) can be accessed via https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-14746 (human skeletal muscle cell datasets; Accession number E-MTAB-14746) and https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-14747 (murine soleus datasets; Accession number E-MTAB-14747). Other data generated in this study are provided in the Supplementary Source Data file. Source data are provided with this paper.
PubMed id: 42613329
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