Eating in the short term is regulated by various mechanisms. Initially, the stretch receptors in the stomach wall detect the distention caused by food entering the stomach. These receptors send signals through the afferents of the vagus nerve to the solitary nucleus in the medulla. From there, the information is transmitted to different brain regions, including the hypothalamus. This communication can occur directly or via a relay in the parabrachial nucleus. The purpose is to coordinate autonomic responses to the ingested material and create conscious awareness of stomach fullness in the thalamus and cortex. The major targets of these signals in the hypothalamus are the paraventricular, dorsomedial, and arcuate nuclei, as well as the lateral hypothalamus.

In addition to stretch receptors, sensory afferents also detect the concentrations of glucose and lipids in the intestines and hepatic portal circulation. These signals are then relayed to the solitary nucleus and subsequently to the hypothalamus, similar to the stretch receptor signals. Furthermore, the stomach and gut release various hormones in response to feeding, such as cholecystokinin, peptide YY, glucagonlike peptide-1 (GLP-1), and ghrelin. These hormones can directly influence hypothalamic cells, as they possess receptors for them. Other brain areas also contain receptors for these hormones and can indirectly affect the hypothalamus. An example of such a region is the area postrema, located just dorsal to the solitary nucleus, which can respond to cholecystokinin and GLP-1, resulting in reduced food intake.

The long-term control of body weight involves the interaction between the nervous and endocrine systems, with the hypothalamus playing a significant role. This section specifically focuses on how the hypothalamus controls the autonomic nervous system, serving as another example of the hypothalamus's involvement in a servomechanism. Adiposity is the regulated parameter in this case. Early studies utilizing lesions and electrical stimulation demonstrated that the ventromedial and ventrolateral hypothalamus play a role in energy homeostasis. Lesions in the ventromedial region lead to an increase in food intake (hyperphagia) and subsequent obesity, while electrical stimulation of the same region reduces feeding behavior. These lesions also affect autonomic activity, resulting in increased parasympathetic and decreased sympathetic tone. These changes lead to elevated blood insulin levels, promoting energy conservation and storage.

Based on these observations, it was initially proposed that the ventromedial hypothalamus contains a satiety center. However, an alternative interpretation suggests that the primary controlled variable may not be eating behavior itself, but rather body weight, specifically adiposity. Modulation of feeding behavior may be just one of several actions employed to maintain a body weight set point. Evidence supporting this concept includes the fact that lesions initially cause dynamic weight gain with hyperphagia, but this is followed by a static period where the higher weight is sustained without hyperphagia. Additionally, animals with lesions in the ventromedial hypothalamus that are provided a fixed (normal) amount of food to prevent hyperphagia still become obese, indicating changes in the regulation of other metabolic processes. Lastly, ventromedial hypothalamic lesions have been found to alter energy expenditure levels.
In the short run, eating is controlled by a number of mechanisms. First, the stomach wall has stretch receptors that signal distention as food fills the stomach. These signals are conveyed by the afferents of the vagus nerve to the solitary nucleus in the medulla. From there the information is relayed to several brain areas, including the hypothalamus, either directly or via a relay in the parabrachial nucleus, to organize autonomic responses to the ingested material, and the thalamus and cortex, for conscious awareness of the fullness of the stomach. In the hypothalamus, the paraventricular, dorsomedial, and arcuate nuclei and the lateral hypothalamus are the major targets of these signals.
Sensory afferents also sense the concentrations of glucose and lipids in the intestines and the hepatic portal circulation and send this information to the solitary nucleus and, from there, to the hypothalamus, in a manner similar to that described for the stretch receptors. In addition, the stomach and gut release a number of hormones in response to feeding, including cholecystokinin, peptide YY, glucagonlike peptide-1 (GLP-1), and ghrelin. Hypothalamic cells have receptors for many of these hormones and can be influenced directly by them. In addition, cells in other brain areas have receptors for these hormones and thus may provide an indirect pathway to the hypothalamus. One such region is the area postrema, which is just dorsal to the solitary nucleus and projects to it. The area postrema is not protected by the blood-brain barrier (it is one of the circumventricular organs), and its neurons respond to cholecystokinin and GLP-1, which leads to decreased food intake.
Control of body weight over the long run is influenced by many factors and involves the interaction of the nervous and endocrine systems. In this section, the focus is on the role of hypothalamus and its control of the autonomic nervous system, which provides another example of how the hypothalamus is part of a servomechanism. In this case, adiposity is the controlled parameter. For further details on the endocrine system’s role, see
Early studies in which researchers used lesions and electrical stimulation provided evidence that the ventromedial and ventrolateral hypothalamus are involved in energy homeostasis. A lesion in the ventromedial region causes an increase in food intake (hyperphagia) that results in obesity, whereas electrical stimulation of the same region decreases feeding behavior. These lesions were also shown to alter autonomic activity, increasing parasympathetic and decreasing sympathetic tone, both of which lead to high blood insulin levels, which in turn promote energy conservation and storage (see ). These observations led to the idea that the ventromedial hypothalamus contains a satiety center. However, an alternative interpretation is that the primary controlled variable may not be simply eating behavior per se but rather body weight and, even more specifically, body fat levels (i.e., adiposity). Thus modulation of feeding behavior may be just one of several actions used to defend a body weight set point. Evidence for this is that although lesions cause an initial period of dynamic weight gain in which hyperphagia is present, this is followed by a static period in which the higher weight is maintained without hyperphagia. Moreover, animals with a lesion in the ventromedial hypothalamus that are fed a fixed (normal) amount of food to prevent hyperphagia nonetheless become obese, which implies changes in the regulation of other metabolic processes. Last, lesions of the ventromedial hypothalamus have been shown to alter levels of energy expenditure.