Neural Circuitry Involved in Food Intake

Food intake involves several aspects of different behaviors, such as hunting for food and decision making. The complexity of feeding behavior is reflected in the number of brain areas involved; several nuclei in the caudal brain stem, hypothalamus, and the corticolimbic area are part of the feeding circuitry.

Despite the large number of brain areas involved in feeding behavior, the hypothalamus is regarded as the main center for regulation of homeostatic feeding in the brain. Within the hypothalamus, the arcuate nucleus is central to the regulation of food intake. The arcuate nucleus contains at least two distinct groups of neurons controlling food intake: neurons that contain the orexigenic neuropeptides agouti-related protein (AgRP) and neuropeptide Y (NPY) and neurons that contain the anorexigenic neuropeptides pro-opiome-lanocortin (POMC) and cocaine- and amphetamineregulated transcript (CART).

These arcuate neurons contain different receptors of hormones that are secreted in the periphery by adipocytes, the pancreas, and the gut in response to nutrients passing or being stored. Leptin, for example, is secreted by adipocytes, reflecting the amount of fat stores in the body. When the body becomes fat, leptin will silence orexigenic neurons and trigger anorexigenic neurons in the arcuate nucleus to secrete a-melanocyte-stimulating hormone (a-MSH) (derived from POMC) and CART to decrease food intake.

In contrast to leptin, the hormone ghrelin, which is released from the (empty) stomach and which has been associated with the anticipation of meals, activates NPY/AgRP neurons and inhibits POMC/CART neurons in the arcuate nucleus. The neurons of the arcuate nucleus project to several nuclei within the hypothalamus, such as the paraventricular (PVN) and the lateral hypothalamic (LHA) nuclei, which also receive and send information from and to the caudal brain stem and corticolimbic areas.

In addition to the anorexigenic and orexigenic neuropeptides in the arcuate nucleus, within the PVN corticotropin-releasing hormone (CRH) and within the LHA melanin-concentrating hormone and orexin(s) are peptides also involved in food intake regulation. Within the brain stem, groups of catecholamine cell groups are localized that project to the hypothalamus and are important for the regulation of feeding behavior, for example, in response to a glucoprivation.

In the brain stem, integration of signals from the periphery (such as cholecystokinin [CCK]) takes place, carrying information on gastrointestinal distention and presence of meals in the gastrointestinal tract and signals from the hypothalamus indicating long-term nutritional status. For instance, leptin and a-MSH affect meal size, probably by determining the sensitivity for CCK at the level of the brain stem, which is released when fat-containing foods reach the duodenum.

Furthermore, within the corticolimbic area, the amygdala and nucleus accumbens are implicated in the evaluation of taste and rewarding aspects of food. Taken together, this complex neural circuitry holds many brain areas, in which neuropeptides and neurotransmitters convey information important for the regulation of feeding behavior.

The brain, however, does not function on its own. To maintain a stable body weight, food intake needs to be tuned to the needs of the peripheral body. This means that when fat stores are increasing or depleting, satiety or hunger factors (e.g., hormones) are produced by different organs to change feeding behavior. For example, leptin that is secreted from adipose tissue acts on its receptor in the arcuate nucleus to decrease food intake. In addition, glucocorticoids secreted by adrenals in response to fasting act as factors to adjust feeding behavior.