The hypothalamus and energy balance

In recent years the growing number of molecules implicated in energy homeostasis has raised nearly limitless possibilities for how body-weight regulation might occur. To better understand how energy homeostasis can be achieved, we describe the roles of individual hormonal and neuropeptide signalling pathways in the control of food intake and the means by which obesity can arise from defects in their function. The hypothalamus links the sensing of nutrients to the control of metabolism and feeding behaviour. Disruptions in the mechanisms of central nervous system (CNS) nutrient-sensing alter these homeostatic responses and contribute to the pathophysiology of obesity and type 2 diabetes mellitus. Experimental and epidemiological studies suggest that sleep loss may also play a role in the increased prevalence of diabetes and obesity. The molecular components of the circadian clock are present in the anterior hypothalamus. It is not therefore surprising that there is a close link between sleep and energy metabolism. In this review we also focus on physical exercise as a mechanism to restore physiological rhythm preventing hyperphagia and obesity in humans. Given its ability to reduce cerebral energy demands and therefore promote sleep, physical exercise could be beneficial for maintaining brain function and improving brain plasticity.