2 Neuroscience2.7 Neural circuits
2.7.1.1 Appetite, hunger and thirst
2 min read2 figures
Written by Resident Doctor Committee · Published
The arcuate nucleus
The arcuate nucleus lies beside the median eminence, where it detects circulating signals through two opposing groups of neurones.
Population | Driven by | Action |
|---|---|---|
Neuropeptide Y (NPY) and agouti-related peptide (AgRP) neurones | Energy deficit, ghrelin, falling leptin | NPY is the most potent central stimulant of intake and lowers energy expenditure; AgRP blocks melanocortin-4 receptors (MC4R), cancelling their satiety signal |
Pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) neurones | Leptin, insulin | Alpha-melanocyte-stimulating hormone (alpha-MSH), cleaved from POMC, activates MC4R to produce satiety |
Alpha-MSH, CART, corticotrophin-releasing hormone and oxytocin all reduce intake, opposing NPY.
The arcuate nucleus has the highest hypothalamic leptin receptor density and is the first-order leptin sensor.
The paraventricular nucleus is the second-order MC4R relay that receives arcuate output.
Lateral and ventromedial hypothalamus
In the dual centre model, the ventromedial nucleus is the satiety centre and the lateral hypothalamus is the feeding centre.
Destroying the ventromedial nucleus causes overeating and obesity, while destroying the lateral hypothalamus causes aphagia.
The model is incomplete, because lesions also damage passing fibres.
Orexin (hypocretin) is made in the lateral hypothalamus and raises appetite and arousal.
Loss of orexin neurones causes narcolepsy with cataplexy, with low cerebrospinal fluid hypocretin-1.
Gut signals
Ghrelin is made in the stomach, peaks before meals and is the only circulating gut hormone that raises appetite.
Ghrelin acts on growth hormone secretagogue receptors in the arcuate nucleus to excite NPY and AgRP neurones.
Signal | Source and timing | Action |
|---|---|---|
Cholecystokinin | Upper small intestine, released during a meal | Short-term satiety that ends eating, partly by damping hypothalamic NPY drive |
Glucagon-like peptide 1 (GLP-1) | Intestinal L cells and nucleus tractus solitarius neurones | Incretin that amplifies insulin release when glucose is high; slows gastric emptying; signals satiety through vagal and brainstem pathways |
Peptide YY (PYY) | L cells of the distal ileum and colon; rises in proportion to calories eaten, with PYY3-36 peaking 1 to 2 hours after a meal | Lasting satiety, by acting on Y2 receptors to inhibit arcuate NPY neurones |
Semaglutide and liraglutide are long-acting GLP-1 analogues.
Adiposity signals
Leptin is secreted mainly by white adipose tissue as the long-term adiposity signal.
Leptin levels rise with fat stores and fall with fasting.
Leptin inhibits arcuate NPY neurones and stimulates POMC neurones.
Congenital leptin deficiency causes hyperphagia and obesity, which recombinant leptin corrects.
Common obesity usually involves high leptin with reduced responsiveness, not leptin deficiency.
Insulin from pancreatic beta cells is the other adiposity signal: its basal level rises with fat mass.
Insulin crosses the blood-brain barrier to arcuate receptors and reduces intake.
Thirst
The subfornical organ and the organum vasculosum of the lamina terminalis lack a full blood-brain barrier, so they detect circulating signals such as angiotensin II.
Supraoptic and paraventricular neurones release vasopressin through the posterior pituitary to conserve water.
Primary polydipsia in psychiatric illness can cause dangerous hyponatraemia.