Neural plasticity and the regulation of energy balance

Energy homeostasis crucially depends on specialized brain circuits that process signals from peripheral organs and the environment to control food intake and energy expenditure. While much detail of this regulatory network has been elucidated in recent years, it is still poorly understood why some humans can maintain their body weight constant over most of their adult life, while others experience substantial gains in weight. These changes in body weight often appear difficult to reverse, both in humans and rodents, indicating that the underlying regulatory circuits may be altered in a very stable way. Such a “memory formation” of a new body weight set point may rely on plastic changes occurring in the brain circuits controlling energy balance. These plastic changes may be brought about by altering the connectome of these circuits, i.e., changing their wiring diagram or by altered neural genesis in the hypothalamus, a brain region key to body weight control. We now know that cell proliferation in the hypothalamus continues into adulthood and that it is responsive to growth factors. There is furthermore evidence that alterations in hypothalamic neural genesis can affect bodyweight. However, we still know only very little about the identity, fate and origin of hypothalamic cells that are either exogenously induced or constitutively born during adulthood. Progress in these areas will be presented.