Paraventricular nucleus (PVN) neurons expressing the melanocortin 4 receptor (MC4R) integrate hormonal and neuronal information concerning energy availability and engage neural circuitry controlling feeding, metabolism, and neuroendocrine function in response to changes in body weight and stored energy. Thereby, the dynamic activity of PVN MC4R neurons may serve as a neural representation of body weight “set point.” Here, we demonstrate that PVN MC4R neuronal activity is bidirectionally regulated by changes in energy state, as neuronal activity is gradually suppressed during fasting and increased in response to refeeding. Together, these findings provide a framework for understanding how hunger and satiety are controlled within critical neurons involved in energy homeostasis.