Fat-brain connections: Adipocyte glucocorticoid control of stress and metabolism

Glucocorticoids act via multiple mechanisms to mobilize energy for maintenance and restoration of homeostasis. In adipose tissue, glucocorticoids can promote lipolysis and facilitate adipocyte differentiation/growth, serving both energy-mobilizing and restorative processes during negative energy balance. Recent data suggest that adipose-dependent feedback may also be involved in regulation of stress responses. Adipocyte glucocorticoid receptor (GR) deletion causes increased HPA axis stress reactivity, due to a loss of negative feedback signals into the CNS. The fat-to-brain signal may be mediated by neuronal mechanisms, release of adipokines or increased lipolysis. The ability of adipose GRs to inhibit psychogenic as well as metabolic stress responses suggests that (1) feedback regulation of the HPA axis occurs across multiple bodily compartments, and (2) fat tissue integrates psychogenic stress signals. These studies support a link between stress biology and energy metabolism, a connection that has clear relevance for numerous disease states and their comorbidities.