Glucocorticoids, stress and obesity

Obesity and the associated metabolic syndrome have been suggested to be the consequence of a maladaptation to chronic stress exposure mediated by a dysregulation of neuroendocrine axes. The hypothalamic–pituitary–adrenal (HPA) axis represents the major hormone system responsible for maintenance of the homeostatic balance in response to stress. The brainstem nuclei and the limbic regions are strongly involved in stressor neural processing and represent a regulatory network for the HPA axis. Moreover, the same neuroendocrine stress centers are involved in the regulation of feeding behavior following acute and chronic stress exposure. Studies performed in experimental animals suggest that consumption of so-called comfort foods, while favoring an adaptation to the detrimental impact of chronic stress on the reward system, may, in turn, lead to the rapid development of obesity. Available data also indicate that the endocannabinoid system modulates the HPA axis and that its type 1 receptors, which are extensively localized in the hypothalamus and in limbic structures, are involved in the regulation of the stress response and the reward mechanisms. Based on extensive clinical experience and studies performed in experimental animals, we developed the concept that there is a specific phenotype of individuals who may become obese as a result of exposure to major stressful events.