Ghrelin is a peptide hormone that is synthesised by endocrine glands in the stomach. Ghrelin is known to stimulate the release of growth hormone by activation of the growth hormone secretagogue receptor. However, it is also thought that ghrelin can act to stimulate appetite. Ghrelin is released in response to a negative energy balance and causes increased food intake in an effort to replenish energy reserves. It does this by stimulation of receptors in the hypothalamus which cause the release of the neuropeptide Y and agouti-related peptide. Rats administered ghrelin increase bodyweight by decreasing the duration between meals, and thus ghrelin appears to be a potent orexigenic hormone. Circulating levels of ghrelin rise prior to meals and fall once food has been ingested suggesting that circulating levels of the hormone accurately mirror its secretion from the intestinal tract.
Long term circulating ghrelin levels are inversely associated with the size of the adipose store in individuals. As weight loss occurs ghrelin levels increase, suggesting that ghrelin may be responsible for the increased desire to eat once calorie restriction or exercise deplete energy reserves. Research shows that subjects who lost weight by exercise, but maintained calorie levels still had increases in ghrelin levels. Baseline levels of ghrelin correlate with bodyweight independent of calorie intake, and rise and fall based on weight changed from that baseline level. Obese subjects tend to have relatively low levels of circulating ghrelin when compared to lean individuals and overfeeding mice reduces the expression of ghrelin mRNA in the gastrointestinal tract. If ghrelin levels are linked to energy reserves it might suggest a regulatory role for leptin.
Circulating ghrelin levels appear to be suppressed relative to the amount of energy consumed. For example research has shown that in laboratory animals, a higher energy meal tend to suppress ghrelin more than a lower energy meal. Little is known about how individual nutrients affect the secretion or suppression of ghrelin. It is known for example that protein, carbohydrates and fat have differing effects on other gut hormones (such as cholecystokinin) and so it may be that this is also true for ghrelin. In rats it appears that all types of micronutrients suppress ghrelin, but that high carbohydrate beverages suppress ghrelin to a greater extent than high fat beverages. Ghrelin may also be suppressed by other hormones that rise with food ingestion such as insulin, cholecystekinin, peptide YY or glucagon-like peptide 1.
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