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[Physiology](https://durgical.com/en/physiology/) · [Endocrine](https://durgical.com/en/physiology/#s-endocrine)

# 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](https://durgical.com/en/anatomy/hypothalamus/) · [Stomach](https://durgical.com/en/anatomy/stomach/) · [Ileum](https://durgical.com/en/anatomy/ileum/) · [Duodenum](https://durgical.com/en/anatomy/duodenum/) · [Pancreas](https://durgical.com/en/anatomy/pancreas/)

## Key points

- Leptin: from adipocytes, proportional to fat mass; stimulates POMC (satiety) and inhibits NPY/AgRP (hunger).
- Ghrelin: from the gastric fundus; rises before meals and falls after eating; stimulates hunger and GH. The only gut hormone that increases appetite.
- Incretins: GLP-1 (L cells, ileum and colon) and GIP (K cells, duodenum) raise insulin only when glucose is high (glucose-dependent).
- Incretin effect: oral glucose triggers far more insulin than the same glycemia given intravenously; it is reduced in type 2 diabetes.
- GLP-1 also slows gastric emptying, lowers glucagon and increases satiety; DPP-4 inactivates it within minutes.
- Common obesity = leptin resistance (high leptin). MC4R mutations are the most frequent monogenic obesity.

## 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](https://durgical.com/en/conditions/obesity/) | Adipose tissue | Fat mass, feeding | ↓ (long term) |
| [Insulin](https://durgical.com/en/conditions/type-2-diabetes-mellitus/) | Beta cells | Glucose, amino acids | ↓ |
| Ghrelin | Stomach (fundus) | Fasting, empty stomach | ↑ |
| [GLP-1 and PYY](https://durgical.com/en/conditions/type-2-diabetes-mellitus/) | 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.

## Memory aid

Ghrelin growls from the stomach, leptin reports the savings from the fat, and GLP-1 closes the kitchen.

## 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.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/physiology/appetite-hormones-leptin-ghrelin-and-incretins/)

## See it in 3D

The structures of Durgical's 3D anatomy where it happens.

- [Hypothalamus](https://durgical.com/en/anatomy/hypothalamus/)
- [Stomach](https://durgical.com/en/anatomy/stomach/)
- [Ileum](https://durgical.com/en/anatomy/ileum/)
- [Duodenum](https://durgical.com/en/anatomy/duodenum/)
- [Pancreas](https://durgical.com/en/anatomy/pancreas/)

## Related topics

- [Energy balance, food intake and obesity](https://durgical.com/en/physiology/energy-balance-food-intake-and-obesity/)
- [Functions of the hypothalamus](https://durgical.com/en/physiology/functions-of-the-hypothalamus/)
- [Gastrointestinal hormones](https://durgical.com/en/physiology/gastrointestinal-hormones/)
- [Islets and insulin: secretion and actions](https://durgical.com/en/physiology/islets-and-insulin-secretion-and-actions/)
- [Growth hormone and IGF-1](https://durgical.com/en/physiology/growth-hormone-and-igf-1/)
- [Gastric motility and emptying](https://durgical.com/en/physiology/gastric-motility-and-emptying/)

## Related conditions

- [Obesity](https://durgical.com/en/conditions/obesity/)
- [Metabolic syndrome](https://durgical.com/en/conditions/metabolic-syndrome/)
- [Type 2 diabetes mellitus](https://durgical.com/en/conditions/type-2-diabetes-mellitus/)

## In Biochemistry

- [Leptin, appetite and obesity](https://durgical.com/en/biochemistry/topics/leptin-appetite-and-obesity/)
- [G protein-coupled receptors and cAMP](https://durgical.com/en/biochemistry/topics/g-protein-coupled-receptors-and-camp/)
- [Insulin signalling](https://durgical.com/en/biochemistry/topics/insulin-signalling/)
- [Fed, fasting and starvation states](https://durgical.com/en/biochemistry/topics/fed-fasting-and-starvation-states/)

## In Pharmacology

- [Metformin](https://durgical.com/en/pharmacology/metformin/)

[← All of physiology](https://durgical.com/en/physiology/)

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](https://openstax.org/books/anatomy-and-physiology-2e/pages/17-10-organs-with-secondary-endocrine-functions) (OpenStax (Rice University), 2022); [24.6 Energy and Heat Balance](https://openstax.org/books/anatomy-and-physiology-2e/pages/24-6-energy-and-heat-balance) (OpenStax (Rice University), 2022); [Epidemiologic and Etiologic Considerations of Obesity](https://www.ncbi.nlm.nih.gov/books/NBK585067/) (StatPearls (NCBI Bookshelf), 2024); [Metabolic Syndrome](https://www.ncbi.nlm.nih.gov/books/NBK459248/) (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.

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Source: https://durgical.com/en/physiology/appetite-hormones-leptin-ghrelin-and-incretins/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/physiology/appetite-hormones-leptin-ghrelin-and-incretins/