Hunger and Appetite
Food intake is due to a complex interplay of emotional factors, learned behaviors, CNS regulation, fat cell thermoregulatory effects, and the digestive system. It has become increasingly clear that the intake of food is influenced by what appears to be an adipose “set point,” which results in a relatively stable weight in most individuals despite efforts to change their weight. The ingestion of food occurs in response to need (hunger) or desire (appetite). Hunger describes the complex behavioral responses evoked by depletion of body nutrient stores required for metabolic needs. Studies by Pavlov and his colleagues in the early 1900s emphasized the importance of cortical functions and the vagus nerve through learned behaviors and their associations with food intake. The fact that food-seeking behavior is manifested in the unconditioned state, as in newborn or anencephalic infants or decerebrate animals, emphasizes the important role of lower brain functions, including the reticuloactivating system and hypothalamus.
The digestive system has a major influence on appetite and hunger. A common sensation described by patients as hunger is discomfort localized to the epigastrium and perceived as emptiness, gnawing, or tension. The fact that such ‘hunger pangs’ are experienced by individuals whose stomach has been removed or denervated is evidence that hunger contractions are not simply related to gastric contractions. On the other hand, it is clear that the stomach is the major source of the hormone ghrelin, which is an important stimulant of food intake. This 28 amino acid peptide is released from X/A-like cells in the oxyntic glands of the gastric fundus but is also found in the pancreas and small intestine. It is structurally related to motilin. Its release leads to increased gastric smooth muscle contractions and stimulation of CNS appetite centers that stimulate food intake.
Anorexia is not a common symptom in patients with complete denervation of the small intestine, as occurs in small bowel transplantation. On the other hand, hormones released as part of the phenomenon known as the ileal brake have a significant influence on appetite, including peptide YY3-36, which suppresses food intake. Surprisingly, basal levels and postprandial levels of peptide YY are decreased in obese patients.
A variety of other gut neuropeptides influence food intake. Neuropeptide Y, released from the pancreas as well as the hypothalamus, increases food intake. Insulin can also increase food intake. Cholecystokinin, released primarily from the duodenum, reduces food intake.
In addition to influences from the CNS and digestive system, adipose tissue also regulates appetite. The key appetite suppressant leptin is synthesized and released from adipose tissues. Leptin is a hormone with extraordinarily broad influences on metabolism, growth, angiogenesis, and other functions; it appears to primarily serve as the satiety hormone. Leptin modifies appetite primarily through its release by white adipose tissue but is also synthesized and released by brown adipose tissue, skeletal muscles, the placenta, ovaries, mammary epithelial cells, and bone marrow. In the digestive tract, it is released by cells in the gastric fundus and by gastric chief cells. It acts as an internal modulator of energy homeostasis, metabolism, and cell replication. Although its primary effects are thought to be mediated by its effects on the hypothalamus, especially on serotonin cells, there are leptin receptors throughout the body on many types of cells. It is clear that leptin release is suppressed by fasting, well before fat stores per se are altered, and is increased by stress, insulin, and corticosteroids and, paradoxically, in obese persons.
Fat stores, particularly of brown adipose tissue, also influence appetite. Brown adipose tissue plays a major role in thermogenesis and appears to be regulated by the CNS hormone orexin. It may be more involved with energy expenditure than appetite per se. Orexin is a neuropeptide hormone structurally related to the gut hormone secretin. It is also released from the hypothalamus and is responsible for both arousal and appetite. It increases lipogenesis. In addition to the hypothalamus, it is also present in neurons throughout the CNS. Orexin release is inhibited by leptin and increased by action of the gastric hormone ghrelin. Decreased orexin can lead to a feeling of lowered energy which may cause a person to eat more to acquire energy. Such reflexive food intake in the setting of reduced energy expenditure can contribute to obesity.