Loss of Cyp27A1 activity has also been linked to increased concentrations of active glucocorticoids [54], so one hypothesis could be that pancreatic induction of Cyp27A1 expression, possibly mediated by activation of glucocorticoid receptors [55,56], could help to reduce the impact of increased circulating concentrations of these stress hormones in obesity [57]. This evidence concerns the gene NR3C1 and obesity due to melanocortin 4 receptor deficiency.