L-BAIBA Drives Exercise Gains in Mice, Boosting Performance at 100 mg/kg via PGC1α-PPARδ
Updated
Updated · Nature.com · Aug 18
L-BAIBA Drives Exercise Gains in Mice, Boosting Performance at 100 mg/kg via PGC1α-PPARδ
3 articles · Updated · Nature.com · Aug 18
Summary
Researchers found the exercise-linked metabolite L-BAIBA—not D-BAIBA—was the main driver of muscle adaptation, increasing running performance, mitochondrial capacity, muscle mass and fatigue resistance in mice given 100 mg/kg/day for 6 weeks.
Mechanistically, the study traced those effects to a PGC1α-BAIBA-PPARδ signaling axis: blocking PPARδ erased BAIBA-driven fiber remodeling, mitochondrial protein increases and force gains, while silencing the L-BAIBA-synthesis enzyme ABAT blunted training-induced performance improvements.
In human primary muscle cells, 10 μM L-BAIBA promoted proliferation, differentiation and oxidative fiber markers, and those gene effects required the cell-surface receptor MRGPRD.
Human data linked the molecule to fitness as well: baseline L-BAIBA correlated with VO2peak in 60 volunteers, rose after a 45-minute endurance session, and increased again after a 10-week training program in a separate 33-person cohort.
The findings suggest L-BAIBA acts as an exercise-mimicking metabokine with potential relevance for muscle dysfunction in obesity and type 2 diabetes, though the therapeutic case remains preclinical.