Appetite hormones: leptin, ghrelin and incretins !
- Regulation
- Exam priority: medium
Fat sends leptin to say «we have reserves»; the empty stomach sends ghrelin to say «eat»; the gut sends GLP-1 to say «enough».
Updated 2026-11-01
Also called: Leptin, Ghrelin, GLP-1, GIP, Arcuate nucleus
See it in 3D: Hypothalamus · Stomach · Ileum · Duodenum · Pancreas
What it is
Food intake is controlled by the arcuate nucleus of the hypothalamus, which reads long-term signals of fat stores (leptin, insulin) and short-term signals from the gut (ghrelin, GLP-1, PYY, CCK). Two neuron groups compete: NPY/AgRP neurons drive hunger, POMC neurons drive satiety through α-MSH and the MC4 receptor. Incretins also amplify insulin release after a meal. In common obesity, leptin is high but the brain responds poorly to it.
How it works, step by step
- Fat stores grow → adipocytes release more leptin → it crosses into the arcuate nucleus.
- Leptin activates POMC/CART neurons; α-MSH acts on MC4 receptors in the paraventricular nucleus to reduce intake and raise energy use.
- At the same time, leptin inhibits NPY/AgRP neurons, removing their hunger drive and their block of MC4R.
- Fasting: leptin and insulin fall, ghrelin rises → NPY/AgRP fire → hunger, lower energy expenditure and lower GnRH.
- During a meal, gastric stretch, CCK (duodenum), PYY and GLP-1 (distal gut) signal through the vagus and brainstem to end the meal.
- GLP-1 and GIP reach the beta cell, raise cAMP and amplify glucose-stimulated insulin secretion.
Main appetite signals
| Signal | Source | Stimulus | Effect on appetite |
|---|---|---|---|
| Leptin | Adipose tissue | Fat mass, feeding | ↓ (long term) |
| Insulin | Beta cells | Glucose, amino acids | ↓ |
| Ghrelin | Stomach (fundus) | Fasting, empty stomach | ↑ |
| GLP-1 and PYY | L cells (ileum, colon) | Nutrients in the distal gut | ↓; GLP-1 also ↑ insulin |
| GIP | K cells (duodenum, jejunum) | Glucose and fat | Mainly ↑ insulin |
| CCK | I cells (duodenum) | Fat and protein | ↓ (ends the meal) |
Clinical notes
- Congenital leptin deficiency (rare): extreme early-onset obesity and hypogonadism that respond to leptin replacement.
- Prader–Willi syndrome: very high ghrelin and insatiable hunger.
- After sleeve gastrectomy, ghrelin falls (fundus removed); after gastric bypass, GLP-1 and PYY rise.
- Low body fat (anorexia nervosa, athletes) lowers leptin and GnRH: hypothalamic amenorrhea.
- GLP-1 receptor agonists and DPP-4 inhibitors use the incretin pathway; agonists also reduce appetite.
Test yourself
Think of the answer, then tap the question to see it.
Most people with obesity have high leptin levels. Why do they not lose their appetite?
They are leptin resistant: transport into the brain and signalling in arcuate neurons are reduced, so the high level does not activate satiety pathways enough.
Why does oral glucose release more insulin than intravenous glucose giving the same plasma glucose?
Glucose in the gut releases GLP-1 and GIP, which amplify beta-cell secretion. Intravenous glucose bypasses the gut and the incretin effect.
Why do incretins lower glucose with little risk of hypoglycemia by themselves?
Their insulin effect is glucose-dependent: they amplify secretion only when glucose is elevated, and GLP-1 lowers glucagon only in hyperglycemia.
A woman who is a marathon runner with very low body fat stops menstruating. Which hormonal link explains it?
Low fat lowers leptin and raises hunger signals; the hypothalamus reduces GnRH pulses, so LH, FSH and estradiol fall.
See it in 3D
The structures of Durgical's 3D anatomy where it happens.
Related topics
- Energy balance, food intake and obesity
- Functions of the hypothalamus
- Gastrointestinal hormones
- Islets and insulin: secretion and actions
- Growth hormone and IGF-1
- Gastric motility and emptying
Related conditions
In Biochemistry
- Leptin, appetite and obesity
- G protein-coupled receptors and cAMP
- Insulin signalling
- Fed, fasting and starvation states
In Pharmacology
Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.
Sources: 17.10 Organs with Secondary Endocrine Functions (OpenStax (Rice University), 2022); 24.6 Energy and Heat Balance (OpenStax (Rice University), 2022); Epidemiologic and Etiologic Considerations of Obesity (StatPearls (NCBI Bookshelf), 2024); Metabolic Syndrome (StatPearls (NCBI Bookshelf), 2024); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 72). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).
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Representative model, for educational purposes only.