The interplay between hypothalamic and brainstem nuclei in homeostatic control of energy balance.

Energy balance and body weight are tightly regulated by homeostatic and hedonic systems of the brain. These systems are ultimately finely tuned by hypothalamic and extrahypothalamic neurocircuitry that modulate feeding and the appetite signalling cascade. The hypothalamus has been extensively researched and its role in homeostatic regulation of energy balance is well established. Later on, evidence indicated that extrahypothalamic signalling also has a critical role in regulation of body mass across the lifespan. One of these brain regions was the brainstem and specifically the dorsal vagal complex (DVC), which comprises of the area postrema (AP), nucleus of the solitary tract (NTS) and dorsal motor complex of the vagus (DMV). These brain stem nuclei were shown to also finely tune feeding behaviour through catecholaminergic, glutamatergic, and GABAergic signals. Moreover, these nuclei also receive afferent signals from the viscera through the gut, as well as humoral input from the bloodstream. Therefore, these brain stem nuclei are deemed as the port of entry where initial appetite-related signals are first conveyed and then modulated to the forebrain to hypothalamic and extrahypothalamic regions such as the arcuate nucleus (ARC) and parabrachial nucleus (PBN). Understanding the intricate interactions and projections between hypothalamic and brainstem nuclei is instrumental to comprehend energy balance regulation as a whole and to potentially address metabolic conditions such as diabetes and obesity. Further research in this area may lead to the development of targeted pharmacological and lifestyle intervention strategies that could lead to mitigation of metabolic disorders and/or promote a healthier body mass across the life span.