As discussed previously (here), there are a number of peptides that have been identified within mammals that regulate feeding behaviour. Anorectic peptides that act to reduce food intake include insulin, leptin, somatostatin, bombesin, calcitonin, cholecystokinin, corticotrophin releasing factor and peptide YY. Some of these are involved in the long term-regulation of food intake and metabolism, whereas others are involved in short-term regulation. These peptides act synergistically and their interactions are not fully understood. However, it is known that they regulate food intake in a myriad of ways, including reductions in gastrointestinal motility, inhibition of stomach emptying, reduction in digestive secretions, alterations in feeding behaviour activated in the central nervous system, as well as subtle changes in the metabolism of thermogenesis and energy partitioning. In antagonism to the orectic peptides, there are a number of anorectic peptides, that act to increase feeding behaviour and energy intake.
Ghrelin is a peptide hormone synthesised by the stomach that has both short and long-term appetite stimulatory functions. Ghrelin plasma levels fall in proportion to the energy content of a specific meal, and rise as the food is digested and metabolised. As energy intake falls, ghrelin is released to the circulation where it acts on receptors in the hypothalamus to cause the release of agouti-related peptide and neuropeptide Y. Evidence suggests that satiety peptides such as peptide YY, glucagon-like peptide 1 and cholecystokinin may interact with ghrelin, possibly by inhibiting release following food ingestion. In addition to this short-term regulation, ghrelin plasma levels tend to rise inversely in proportion to the amount of adipose tissue present. As energy reserves are depleted from adipocytes, ghrelin levels increase and stimulate compensatory feeding behaviour. In this way ghrelin can be thought of antagonistic to leptin.
The fact that opioid receptor antagonists inhibit feeding behaviours would suggest that opioids are involved in the regulation of appetite. Mammals have three groups of endogenous opioid compounds which are the proopomelanocortins, the prodynorphins and the proenkephalins. All of these classes of opioids have been shown to increase feeding in mammals via activation of the mu, delta and kappa receptors. Evidence suggests that the opioids stimulate feeding behaviour aimed at particular macronutrients. For example, naloxone an opioid receptor antagonist when administered centrally to rats, decreases the intake of high fat diets. Opioids in rats are known to stimulate the feeding of high intakes of fat in particular. Neuropeptide Y is also known to stimulate appetite when administered centrally to rats. Neuropeptide Y is secreted by the hypothalamus in response to rising ghrelin concentrations and is known to stimulate appetite, decrease physical activity and increase the amount of energy stored as fat.
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