The interplay between stress, circadian clocks, and energy metabolism

In modern societies, the risk of developing metabolic disorders such as obesity or type-2 diabetes is associated with the prevalence of psychosocial stress. In response to an acute stressor, activation of the sympathetic nervous system and the hypothalamus–pituitary–adrenal (HPA) axis releases catecholamines and glucocorticoids (GCs) into the circulation. Such stress responses are also regulated by the endogenous circadian clock adapting physiology and behavior to the environmental changes brought about by the Earth’s rotation around its axis. Thus, the timing of stress may critically affect adaptive responses to and the pathological effects of repetitive stressor exposure. The Oster lab has studied the role of different tissue clocks in the regulation of HPA axis activity in mice. They further characterised the impact of predictable social defeat stress during day- versus nighttime on metabolic regulation and HPA axis activity. Repeated nighttime stressor exposure leads to alterations in food metabolization and reduced HPA axis activity with lower circulating adrenocorticotropic hormone (ACTH) and GC concentrations at the time of predicted stressor exposure. Together, these findings suggest a circadian gating of stress adaptation at the level of the HPA axis with impact on metabolic homeostasis.