L-β-aminoisobutyric acid (L-BAIBA) in combination with voluntary wheel running exercise enhances musculoskeletal properties in middle-age male mice

Contracting skeletal muscles secrete the metabolite L-β-aminoisobutyric acid (L-BAIBA), which when supplemented in the diet can mitigate disuse-induced musculoskeletal dysfunction. However, the effects of L-BAIBA supplementation alone and combined with exercise on cardiac and musculoskeletal properties are currently unknown. We hypothesized that exercise with L-BAIBA supplementation would promote greater cardiac and musculoskeletal benefits than exercise alone. To investigate this hypothesis, we subjected 12-month-old (as a model of middle-age) male C57BL6 mice to voluntary wheel running (VWR) with L-BAIBA (100mg/kg/day) (VWR+L-BAIBA), VWR alone, L-BAIBA alone, or none (CTRL) for three months. After the intervention, conscious electrocardiogram showed slightly prolonged QTc in VWR+L-BAIBA mice compared to CTRL (p<0.05). Soleus muscles from VWR+L-BAIBA, but not VWR, were larger, contracted more forcefully, and contained more slow-oxidative type I myofibers compared to CTRL (p<0.05). In EDL muscle, VWR but not VWR+L-BAIBA improved fatigue resistance and caffeine-induced recovery (p<0.05). In bone, VWR+L-BAIBA but not VWR showed lower bone marrow adiposity, higher trabecular thickness, and connectivity, smaller bone diameter and Moment of Inertia, but higher Modulus of Elasticity than CTRL (p<0.05), suggesting L-BAIBA delays aging-induced periosteal expansion due to better bone material qualities. These findings suggest a physiological interaction between exercise and L-BAIBA supplementation to improve soleus muscle and bone properties and reduce bone marrow adiposity.