Lesions of the lateral hypothalamus suppress food intake and lead to a decrease in body weight, potentially resulting in starvation. Conversely, electrical stimulation of the medial forebrain bundle in the lateral hypothalamus promotes exploratory behavior and eating when food is present. This stimulation also activates dopamine-dependent reward pathways, which play a role in the incentive effects of natural rewards like food and sex, as well as the rewarding effects of most drugs of abuse. While the lateral hypothalamus is believed to contain a feeding center, it is important to consider the influence of dopaminergic axons from substantia nigra neurons that pass near the lateral hypothalamus, as their loss or stimulation may account for the observed effects. Nonetheless, neurons in the lateral hypothalamus produce peptides such as orexin that affect feeding behavior, indicating its involvement in energy homeostasis.

Recent studies have identified various hormones and neuropeptides involved in feeding and the control of body weight, shedding light on the interactions between the endocrine and nervous systems that regulate energy balance. In normal individuals, blood insulin levels are correlated with adiposity, and leptin levels, a hormone released by white adipose tissue, also reflect adiposity. High levels of leptin suppress food intake and promote catabolic processes, including the loss of fat tissue, while low levels of leptin have the opposite effect. Similarly, elevated insulin levels promote energy storage.

The hypothalamus, particularly the arcuate nucleus, plays a crucial role in the regulation of body weight through the actions of leptin and insulin. Neurons in the arcuate nucleus express receptors for both hormones and can be classified into two major groups. Neurons expressing proopiomelanocortin (POMC) and cocaine-and amphetamine-related transcript (CART) are stimulated by leptin and insulin, leading to increased catabolism. In contrast, neurons expressing neuropeptide Y (NPY) and agouti-related peptide (AgRP) trigger anabolic processes but are inhibited by leptin and insulin. Therefore, elevated body fat levels result in high leptin and insulin levels, which increase the activity of POMC and CART-expressing neurons, promoting catabolism, and decrease the activity of NPY and AgRP-expressing neurons, reducing anabolism. This feedback mechanism helps maintain body fat levels at their set point. Conversely, reducing body fat levels initiates a series of events opposite to the described process, increasing body fat levels back to the original set point.

The specific pathway responsible for mediating the actions of these arcuate neurons is not yet fully understood. However, the projection from the arcuate nucleus to the paraventricular hypothalamic nucleus appears to be a critical step. Paraventricular neurons contain oxytocin and play a role in lactation and uterine contractions during labor. However, the paraventricular neurons involved in body weight regulation are a distinct subset that project down to the brainstem and spinal cord. These neurons likely synapse with autonomic and preautonomic nuclei that control parasympathetic vagal fibers to the pancreas, stimulating insulin release, as well as sympathetic fibers, which inhibit insulin release.

Water intake is also regulated by a servomechanism. Fluid intake is influenced by blood osmolality and volume.
In contrast to lesions of the ventromedial hypothalamus, those of the lateral hypothalamus suppress food intake (hypophagia) and lead to a decrease in body weight; indeed, animals can starve to death after such lesions. Conversely, electrical stimulation of the medial forebrain bundle in the lateral hypothalamus evokes exploratory behavior and eating, if food is present. This stimulation also provides a dopamine-dependent reward that mediates the incentive effects of natural rewards (food, sex) as well as the rewarding effects of most drugs of abuse. These observations led to the view that the lateral hypothalamus contains a feeding center. This interpretation, however, is complicated by the fact that the dopaminergic axons of substantia nigra neurons pass just lateral to the lateral hypothalamus on their way to the striatum, and so loss or stimulation of these fibers could account for the effects produced in these experiments. However, lateral hypothalamic neurons have been found to synthesize peptides, such as orexin, that affect feeding behavior, and so the lateral hypothalamus probably does play a role in energy homeostasis.
In newer studies, investigators have identified a number of hormones and neuropeptides involved in feeding and control of body weight, and many of the interactions between the endocrine and nervous systems that underlie energy homeostasis have been clarified.
In normal individuals, blood insulin levels are correlated with adiposity (in addition to varying acutely with blood levels of glucose and other substances). Similarly, the level of the protein leptin, a hormone released by adipocytes (primarily those forming white adipose tissue), is correlated with adiposity. High levels of leptin inhibit food intake and stimulate catabolic processes, including loss of fat tissue, whereas low leptin levels trigger the reverse actions. Similarly, high insulin levels promote energy storage processes.
The ability of leptin and insulin to regulate body weight has been linked to their actions on the hypothalamus, particularly the arcuate nucleus, whose neurons express receptors for both hormones (see also ). Two major classes of arcuate nucleus neurons that respond to leptin and insulin have been identified. Neurons that express proopiomelanocortin (POMC) and cocaine-and amphetamine-related transcript (CART) are stimulated by leptin and insulin, and their activity leads to increased catabolism. In contrast, the activity of a second group of neurons, those that express neuropeptide Y (NPY) and agouti-related peptide (AgRP), triggers anabolic processes but is inhibited by leptin and insulin. Thus increased body fat levels lead to high leptin and insulin levels, which in turn both (1) increase the activity of POMCand CART-expressing neurons, leading to increased catabolism, and (2) decrease the activity of NPYand AgRP-expressing neurons, leading to decreased anabolism; both of which act to return body fat levels to their set point. Lowering body fat levels would result in a sequence of events opposite to that just described to increase body fat levels to their original level or set point.
The efferent limb that mediates the actions of these sets of arcuate neurons is not fully worked out. However, the arcuate nucleus projection to the paraventricular hypothalamic nucleus appears to be an important step in the pathway. Paraventricular neurons contain oxytocin. Many of them project to the posterior pituitary gland and are involved in lactation and uterine contractions during labor (see ). However, the paraventricular neurons involved in body weight regulation are a distinct subset of neurons that project down to the brainstem and spinal cord, where they probably synapse with autonomic and preautonomic nuclei that control parasympathetic vagal fibers to the pancreas, which act to stimulate insulin release, and sympathetic fibers, which act to inhibit its release.
Regulation of Water Intake
Water intake also depends on a servomechanism. Fluid intake is influenced by blood osmolality and volume (