Glucocorticoid action in osteoblasts and systemic energy metabolism

Glucocorticoids are pleiotropic hormones with potent regulatory roles in tissue homeostasis, electrolyte balance, immune defence, central nervous function, stress response, growth and development, as well as fuel metabolism. Clinically, glucocorticoids are widely used for their unsurpassed anti-inflammatory and immunomodulatory effects. However, chronic exposure to excessive levels of endogenous or exogenous glucocorticoids causes insulin resistance, glucose intolerance, dyslipidaemia, central obesity, muscle wasting and bone loss. Topical studies in rodents have demonstrated that the effects of chronic hypercortisolism on systemic fuel metabolism and body composition are in part mediated through their actions on osteoblasts. Interestingly, targeted abrogation of glucocorticoid signalling in osteoblasts also attenuates the effects of high fat intake as well as ageing on body composition and systemic fuel metabolism. Here we briefly review the physiology of glucocorticoid action and discuss emerging concepts regarding the molecular mechanisms underlying the adverse effects of glucocorticoid excess.