The dark side of vitamin D system: unraveling its impact on skeletal muscle homeostasis

The maintenance of skeletal muscle is of pivotal importance, as its loss is ofen associated with progressive pathologies, generally worsening the prognosis. Vitamin D (VD) defciency is associated with a decline in muscle mass and performance in various diseases. Therefore, VD supplementaton has been proposed to counteract skeletal muscle loss. However, VD administraton has yielded contrastng results, highlightng the need for a deeper comprehension of VD actvity on skeletal muscle. We showed how variously hydroxylated VD metabolites elicit contrastng efects both on skeletal muscle trophism and metabolism in vitro, thus providing a putatve explanaton about the opposite outcome of VD supplementaton in vivo. Specifcally, our fndings revealed that calcidiol (25VD) and its precursor cholecalciferol (VD3) exhibit ant-atrophic actvity, whereas calcitriol (1,25VD) negatvely impinges on myotube size. Furthermore, we found that the main VD carrier, named Vitamin D Binding Protein, induces atrophy per se, further complicatng the scenario.