Glucocorticoid receptor action in metabolic and neuronal function [version 1; referees: 3 approved]

Glucocorticoids via the glucocorticoid receptor (GR) have effects on a variety of cell types, eliciting important physiological responses via changes in gene expression and signaling. Although decades of research have illuminated the mechanism of how this important steroid receptor controls gene expression using and cell culture–based approaches, how GR responds to changes in vitro in external signals under normal and pathological conditions remains in vivo elusive. The goal of this review is to highlight recent work on GR action in fat cells and liver to affect metabolism and the role GR ligands and receptor in vivo phosphorylation play in calibrating signaling outputs by GR in the brain in health and disease. We also suggest that both the brain and fat tissue communicate to affect physiology and behavior and that understanding this “brain-fat axis” will enable a more complete understanding of metabolic diseases and inform new ways to target them. 1 2