Leptin and ghrelin are two hormones with opposing effects on appetite. Leptin, secreted by adipose tissue, is a long-term satiety signal \u2014 it informs the brain about the state of the energy reserves. Ghrelin, secreted mainly by the stomach, is a short-term hunger signal \u2014 it intensifies appetite before a meal. Together they form the basis of the hormonal regulation of appetite.<\/p>\n
This article is educational in character and constitutes a review of the published scientific literature on the endocrinology of appetite regulation. It is not medical or dietary advice. It describes hormonal mechanisms, not guidance for action. Some of the data cited come from human studies, some from models.<\/em><\/p>\n Leptin was discovered in 1994 as the product of the ob<\/em> gene, and its name comes from the Greek leptos<\/em> \u2014 “thin” (Zhang et al., 1994). It is a protein hormone secreted above all by white adipose tissue<\/strong>, in an amount roughly proportional to the mass of stored fat<\/strong>. The larger the fat reserves, the higher the leptin concentration.<\/p>\n The function of leptin is to inform the brain about the state of the long-term energy reserves. It acts as an “adipostat” signal \u2014 a system regulating the amount of adipose tissue much as a thermostat regulates temperature. When the reserves are high, high leptin signals satiety to the hypothalamus: it suppresses appetite and sustains energy expenditure. When the reserves fall (e.g. during weight loss), the leptin concentration drops sharply, and the brain reads this as a signal of deficit \u2014 it intensifies hunger and lowers expenditure.<\/p>\n Importantly, leptin is a stronger signal of deficit than of excess<\/strong>. Its fall during weight loss triggers a vigorous defensive response, whereas its rise during weight excess does not suppress appetite equally effectively \u2014 which leads directly to the phenomenon of leptin resistance.<\/p>\n Leptin also serves functions beyond appetite itself: it participates in the regulation of reproduction (it signals whether the energy reserves are sufficient for reproduction), the modulation of the immune system and sexual maturation. This makes it a hormone linking the body’s energy state with other physiological systems.<\/p>\n Particularly instructive is the contrast between rare congenital leptin deficiency and common leptin resistance. People with a genetic absence of leptin (an extremely rare mutation) experience extreme, uncontrolled hunger from childhood \u2014 and administering leptin restores normal appetite regulation and leads to the normalisation of weight. This is proof that in these cases the leptin signal works<\/em> when it is present. In typical obesity the opposite is true: there is plenty of leptin, but the brain does not respond to it (Friedman and Halaas, 1998). This contrast explains why leptin did not become a treatment for common obesity.<\/p>\n Ghrelin, discovered in 1999, is in many respects the opposite of leptin (Kojima et al., 1999). It is a peptide hormone secreted mainly by the cells of the stomach<\/strong>. Unlike leptin \u2014 a long-term signal \u2014 ghrelin acts in the short term<\/strong>, in the rhythm of meals.<\/p>\n The ghrelin concentration rises before a meal<\/strong>, peaking when the stomach is empty, and falls after eating<\/strong>. This makes it the main hormonal signal that initiates appetite \u2014 it is sometimes called “the hunger hormone”. Ghrelin acts on the hypothalamus, stimulating the neurons that intensify appetite, and participates in the reward signalling associated with food.<\/p>\n The name “ghrelin” in fact reflects its originally discovered function \u2014 it comes from the root meaning “growth hormone release”. Ghrelin is a strong, natural stimulator of growth hormone secretion, acting through the GHS-R receptor \u2014 the same one on which the peptide secretagogues<\/a> studied in the context of the somatotropic axis act. Appetite regulation and growth hormone regulation thus meet in a single molecule, which neatly illustrates how the body’s metabolic pathways intertwine.<\/p>\n Ghrelin is also connected with body weight regulation over the longer term. In weight-loss research, the ghrelin concentration has been observed to rise after weight loss<\/strong> and may remain elevated \u2014 which is among the mechanisms that intensify hunger, described in the context of metabolic adaptation<\/a> and the defence of body weight<\/a> (Cummings et al., 2002).<\/p>\n The simplest way to frame the relationship between these hormones is as a pair of opposite sign and different time scale.<\/p>\nLeptin \u2014 the hormone of reserves and satiety<\/h2>\n
Ghrelin \u2014 the hunger hormone<\/h2>\n
Leptin and ghrelin \u2014 two opposing signals<\/h2>\n