Figure 2. Hcrt system as a sensor of metabolism.

Hcrt neurons are inhibited by leptin and activated by ghrelin and glucose. In addition, they received indirect circadian inputs that are integrated with metabolic signals to modulate sleep and metabolism. Chronic short sleep perturbation induces metabolic changes including lowering leptin levels and increasing ghrelin levels that directly increase the activity of the Hcrt system. This increase in Hcrt activity promotes consummatory behaviours (food, drug), energy expenditure (via higher locomotor activity and metabolic rate) and sleep-to-wake transitions. Consequently, activation of the Hcrt system inhibits sleep and energy conservation. Triggering activity of the Hcrt neuronal circuit by circulating metabolic factors may then result in a positive feedback loop, which worsens existing sleep perturbation symptoms. This positive loop is inhibited by increasing sleep pressure (a consequence of sleep demand) and may result in a stabilization of the sleep–wake cycle. V: 3rd ventricle.