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Next Lesson - The Adrenal Glands and Adrenal Disorders
Contents
Abstract
- Appetite is controlled by a network of brain areas, centred on the arcuate nucleus (a cluster of neurones in the hypothalamus)
- Appetite-stimulating (orexigenic) neurones act to stimulate appetite, and appetite-suppressing (anorexigenic) neurones act to suppress appetite
- There are many peptide hormones involved in appetite control, including neuropeptide-Y, agouti-related peptide, pro-opiomelanocortin (POMC), ghrelin, and peptide YY (PYY)
- Ghrelin is released in response to an empty stomach to stimulate appetite
- Leptin and PYY both act to suppress appetite
Core
Appetite is controlled by a network of brain areas. The arcuate nucleus (a cluster of neurones in the hypothalamus) is the key one. It contains neurones that prompt feelings of hunger and neurones that produce the feeling of ‘fullness’ (satiety), helping to regulate the amount and the timing of food intake.
The arcuate nucleus contains primary neurones that sense metabolite (a substance made or used in metabolism, such as glucose) and hormone levels. Secondary neurones in other areas of the hypothalamus receive inputs from these arcuate primary neurones, and co-ordinate an appropriate response via autonomic and neuroendocrine (nerve-controlled hormone release) pathways, including vagal signalling.
The primary neurones in the arcuate nucleus can be sub-divided into appetite-stimulating (orexigenic) neurones and appetite-suppressing (anorexigenic) neurones.
- Orexigenic neurones: stimulate appetite via the release of neuropeptide-Y and agouti-related peptide.
- Anorexigenic neurones: suppress appetite via the release of POMC (pro-opiomelanocortin) and CART (cocaine- and amphetamine-regulated transcript).
POMC is a prohormone (an inactive precursor). It is a polypeptide (a chain of amino acids) that can be cut into smaller pieces to produce several peptide hormones (β-endorphin, a natural opioid; adrenocorticotropic hormone (ACTH); and α-melanocyte-stimulating hormone (α-MSH)).
- α-MSH acts on melanocortin-4 receptors (the receptors that α-MSH binds to) to suppress the appetite. Rare changes (variants) in the gene for this receptor are the commonest single-gene cause of obesity.
- β-endorphins act on the reward system in the brain and add to the pleasure of eating.
Some regions of the brainstem are also involved in appetite control, but this will not be discussed in this article.
When our stomach is empty, ghrelin (a peptide hormone) is released mainly from the stomach wall. It activates the appetite-stimulating (orexigenic) neurones in the arcuate nucleus, and this stimulates appetite. Once eating occurs, nutrients from the food inhibit ghrelin release. Animal studies suggest that stretch of the stomach wall alone does not do this.
Peptide YY (PYY) (a peptide hormone) is released from L cells (hormone-releasing cells) in the wall of the intestine in response to food. It acts in opposition to ghrelin to suppress appetite.
Leptin (a peptide hormone) is released into the blood by adipocytes (fat cells). The more adipose (fat) tissue the body has, the more leptin is in the blood. Leptin acts by stimulating appetite-suppressing (anorexigenic) neurones and inhibiting appetite-stimulating (orexigenic) neurones in the arcuate nucleus to suppress appetite. This is an example of a feedback mechanism from the body’s fat stores in order to control food intake. In most people with obesity, leptin levels are high but the brain responds poorly to leptin (leptin resistance), so this feedback works less well.
Insulin can suppress appetite in a similar way to leptin, because both hormones act on the arcuate nucleus. Insulin resistance (cells responding poorly to insulin) is associated with obesity. It can lead to type 2 diabetes mellitus when the beta cells (the insulin-making cells) of the pancreas can no longer compensate by making extra insulin.
Amylin (also called islet amyloid polypeptide) is released together with insulin by the beta cells of the pancreas. It is known to suppress appetite. It also reduces glucagon release after meals and slows gastric emptying.
Neurones in the arcuate nucleus are also able to sense the level of glucose and fatty acids in the blood, which is useful when considering whether the appetite needs to be suppressed or stimulated.
Research on the system of appetite control has revealed hormones and receptor targets that are now used as drugs for obesity. NICE recommends semaglutide (Wegovy) and tirzepatide (Mounjaro) for managing overweight and obesity in adults who meet set criteria. Semaglutide acts on the receptor for GLP-1 (glucagon-like peptide 1), a gut hormone that is released from the same L cells as PYY after a meal and also reduces appetite. Tirzepatide acts on two gut hormone receptors.
Reviewed by: Dr. Marcus Judge
Quiz
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