NR3C1 and obesity due to melanocortin 4 receptor deficiency: Recent investigations have shown that excessive glucocorticoid action is, in many respects, associated with insulin and leptin resistance, leading to the development of type 2 diabetes, obesity and other metabolic and cardiovascular disorders, the major underlying causes of metabolic syndrome.[7–10] Glucocorticoid receptor (GR) activation stimulates hepatic glucose production, antagonises insulin secretion from pancreatic β-cells and insulin-mediated glucose uptake in peripheral tissues.[11–14] GR activation also promotes lipolysis and fatty acid mobilisation.[15]