Muscle plasticity is influenced by renal function and caloric intake through the FGF23-vitamin D axis.

Abstract

Skeletal muscle, the main metabolic engine in the body of vertebrates, is endowed with great plasticity. The association between skeletal muscle plasticity and two highly prevalent health problems: renal dysfunction and obesity, which share etiologic links as well as many comorbidities, is a subject of great relevance. It is important to know how these alterations impact on the structure and function of skeletal muscle because the changes in muscle phenotype have a major influence on the quality of life of the patients. This literature review aims to discuss the influence of a nontraditional axis involving kidney, bone, and muscle on skeletal muscle plasticity. In this axis, the kidneys play a role as the main site for vitamin D activation. Renal disease leads to a direct decrease in 1,25(OH)2-vitamin D, secondary to reduction in renal functional mass, and has an indirect effect, through phosphate retention, that contributes to stimulate fibroblast growth factor 23 (FGF23) secretion by bone cells. FGF23 downregulates the renal synthesis of 1,25(OH)2-vitamin D and upregulates its metabolism. Skeletal production of FGF23 is also regulated by caloric intake: it is increased in obesity and decreased by caloric restriction, and these changes impact on 1,25(OH)2-vitamin D concentrations, which are decreased in obesity and increased after caloric restriction. Thus, both phosphate retention, that develops secondary to renal failure, and caloric intake influence 1,25(OH)2-vitamin D that in turn plays a key role in muscle anabolism.