High dose dietary vitamin D allocates surplus calories to muscle and growth instead of fat via modulation of myostatin and leptin signaling

Abstract

ABSTRACTObesity is the leading proportional cause for diabetes, heart disease and cancer. Obesity occurs because the body stores surplus calories as fat. Fat cells secrete a hormone, leptin, that modulates energy balance at the brain. Changes in fat mass are mirrored by changes in serum leptin. Increases in leptin cause the brain to decrease appetite and increase energy expenditure. However in obesity, leptin sensitivity is decreased which mutes leptin mediated changes in appetite and energy expenditure. We have limited understanding of what controls leptin production by fat or how sensitive the brain is to leptin. Muscle produces a hormone, myostatin, that plays an analogous role to the role that leptin plays in fat. Absent myostatin leads to increased muscle mass and strength. We also do not know what controls myostatin production or sensitivity. Although fat mass and muscle mass are closely linked, the interplay between leptin and myostatin remains unexplored. Vitamin D improves lean mass via what are thought to be primarily trophic effects at the muscle. Here we show that high dose dietary vitamin D preferentially allocates excess calories to muscle and growth instead of storage as fat by decreasing myostatin production and increasing leptin production and sensitivity. That is, high dose vitamin D improves organismal energy sensing. Obesity, aging and other chronic inflammatory diseases are associated with decreased muscle function and mass. Our work provides a physiologic framework for how high-dose vitamin D would be effective in these pathologies to increase allocation of calories to muscle instead of fat and reveals novel interplay between the myostatin and leptin signaling whereby myostatin conveys energy needs to modulate leptin effects on calorie allocation. Furthermore, our work reveals how physiologic seasonal variation in vitamin D may be important in controlling season-specific metabolism and calorie allocation to fat in winter and muscle in summer.