Peptides that regulate appetite have been identified in the tissues of the gastrointestinal tract, pituitary, pancreas, hypothalamus and general neural tissues of mammals. These peptides tend to show paracrine, autocrine and endocrine functions that synergistically allows the regulation of energy intake in order to help maintain correct body weight despite large fluctuations in short and long-term feeding behaviour. The exact physiological changes cause by a specific peptide often change between the peripheral and central nervous system and some of these responses are not related to appetite. Within the gastrointestinal tract, peptides can cause changes in gastrointestinal locomotion, changes to stomach emptying rates, and the inhibition or secretion of digestive juices. The chemistry of peptides that regulate appetite is complex and not fully understood, but a number of peptides have been identified and their general functions are starting to be reported.
A number of peptide hormones are known to produce an anorectic effect in humans, and of these insulin is one of the most studied. Insulin is a peptide hormone released from the pancreas that has the primary function of glucose disposal to the tissues of the body. Insulin has been shown to act on the hypothalamus where it causes the inhibition of neuropeptide Y, as well as increases the sensitivity of the hypothalamus to external satiety signals such as from cholecystokinin (CCK). However, when insulin is administered peripherally it stimulates further food intake, by decreasing blood glucose levels which is a powerful driver of feeding behaviour. This would suggest that maintaining proper control over insulin levels such that blood sugar homeostasis was correctly maintained, was an important factor in appetite suppression. Any factors that create hypoglycaemia, such as insulin resistance or poor diet, are likely to induce overeating.
Cholecystokinin is another well studied anorectic peptide hormone that appears to regulate food intake by decreasing the size of individual meals. Cholecystokinin is produced in the I cells of the mucosa of the small intestine and is released in response to the presence of chyme rich in undigested protein and fat. Cholecystokinin has a duel role in that it activates receptors in the duodenum to stimulates the release of pancreatic enzymes and bile to aid protein and fat digestion, but also acts on receptors in the stomach where it decreases motility to limit further food intake by decreasing gastric emptying. Rats fed CCK tend to decrease the amount of energy ingested at a particular meal, but increase meal frequency. However, CCK tends to have slightly different effects in different species. Food high in protein and fat therefore tend to create satiety by releasing CCK, but this is a short-term effect that is probably related to a single meal.
Bombesin is a peptide that is found in both the brain and the gut which is involved in the down-regulation of appetite. Bombesin is secreted from the gut and acts on receptors on the G cells of the stomach to prevent hydrochloric acid secretion. Other functions of Bombesin include the ability to regulate body temperature and the regulation of smooth muscle and blood glucose. Calcitonin is a hormone responsible for the regulation of correct calcium levels. Increasing circulating levels in response to a high calcium intake have been shown to decrease further food intake, probably through activation of receptors in the hypothalamus. The calcitonin gene is expressed in the central nervous system as the calcitonin gene-related peptide (CGRP) and this gene is distributed in areas known to be involved with taste and feeding behaviour. Animals injected with CGRP show decreased food intakes and behaviour switched to grooming and resting.
Increasing plasma levels of catecholamines such as adrenaline and noradrenaline are known methods of decreasing feeding behaviour through inhibition of appetite. Corticotrophin releasing factor (CTRF) is a peptide hormone released from the hypothalamus that stimulates the release of adrenocorticotrophin factor (ACTF) from the pituitary gland which subsequently stimulates the release of the catecholamine hormones from the adrenal glands. This results in increased blood glucose levels, heart rate and blood pressure and well as a decreased blood flow to the gastrointestinal tract and increased skeletal muscle flow. Corticotrophin releasing factor is released in response to stress, but it is not clear how it may aid in the regulation of appetite outside of this role. Anorectic drugs such as ephedrine alkaloids, cocaine and amphetamine increase central and peripheral concentrations of adrenaline which explains their clinical effects on weight loss.
Somatostatin is a peptide hormone released from m the stomach, small intestine and pancreas. Release of somatostatin is known to inhibit food intake by decreasing gastric emptying and inhibiting smooth muscle contraction and intestinal blood flow. Leptin is a peptide hormone secreted in proportion to the size of energy contained within the adipose tissue. Leptin acts in the hypothalamus to inhibit the orexigenic hormones (MCH), agouti related peptide (AgRP) and orexin. At the same time leptin stimulates the anorexigenic peptides the melanocortins, cocaine and amphetamine related transcript (CART), thyrotropin releasing hormone and corticotrophin releasing factor. Peptide YY is a hormone produced in the mucosa of the small intestine that is released in proportion to the energy content of the ingested food. Peptide YY is probably involved in short-term energy regulation and energy balance, and some evidence suggests that the signal is down-regulated in obese individuals.
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