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[Biochemistry](https://durgical.com/en/biochemistry/) · Topic

# Leptin, appetite and obesity

Leptin comes from fat tissue and tells the hypothalamus how much fat there is; in obesity it is plentiful but the brain responds poorly.

Updated 2026-11-01

## Key facts

- Adipocytes secrete leptin in proportion to fat mass; it acts on the hypothalamic arcuate nucleus through its receptor (LEPR) and the JAK2–STAT3 pathway.
- It activates POMC neurons (α-MSH → MC4R receptor: less hunger) and inhibits NPY/AgRP neurons (which cause hunger).
- Most people with obesity have high leptin and resistance to its effect, not a lack of leptin.
- Stomach ghrelin rises before meals (hunger); GLP-1, PYY and insulin cause satiety.
- Leptin falls in fasting and malnutrition: energy expenditure, T3 and reproductive function drop.

## In detail

- Long-term signals (fat reserve): leptin and insulin. Short-term signals (each meal): ghrelin, cholecystokinin, GLP-1 and PYY.
- In the arcuate nucleus two neuron populations compete: POMC/CART (appetite-reducing) and NPY/AgRP (appetite-raising); their signals converge on the paraventricular nucleus through the MC4R receptor.
- Leptin resistance in obesity is put down to less transport into the brain, more SOCS3 and PTP1B, and hypothalamic inflammation.
- Fat tissue also releases adiponectin, which improves insulin sensitivity and is low in visceral obesity.
- Excess visceral fat releases fatty acids and cytokines that cause insulin resistance in liver and muscle: the basis of the metabolic syndrome.

**Also called**
Energy balance

## Clinical notes

- Congenital deficiency of leptin or its receptor causes severe obesity from the first months, intense hunger and hypogonadism; leptin deficiency responds to recombinant leptin.
- MC4R mutations are the most common monogenic cause of obesity.
- GLP-1 receptor agonists reduce appetite and are used in type 2 diabetes and obesity.
- Amenorrhoea in athletes and in eating disorders is linked to low leptin from little body fat.

## 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/)
- [Obstructive sleep apnoea](https://durgical.com/en/conditions/obstructive-sleep-apnoea/)
- [Polycystic ovary syndrome](https://durgical.com/en/conditions/polycystic-ovary-syndrome/)
- [Marasmus](https://durgical.com/en/conditions/marasmus/)

## Related

- [JAK–STAT pathway](https://durgical.com/en/biochemistry/topics/jak-stat-pathway/)
- [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/)
- [Aromatase (CYP19A1)](https://durgical.com/en/biochemistry/enzymes/aromatase/)
- [AMP-activated protein kinase (AMPK)](https://durgical.com/en/biochemistry/enzymes/amp-activated-protein-kinase/)
- [mTOR (mechanistic target of rapamycin)](https://durgical.com/en/biochemistry/enzymes/mtor/)

## Test yourself

Think of the answer, then tap the question to see it.

## Which tissue makes leptin, and what does it tell the brain?

Fat tissue; it reports the size of the fat reserve.

## Why does giving leptin not help common obesity?

Because leptin is already high; the problem is hypothalamic resistance to its effect.

## Which arcuate nucleus neurons does leptin stimulate?

POMC neurons, which release α-MSH onto the MC4R receptor and reduce appetite.

## Which stomach hormone rises before meals and causes hunger?

Ghrelin.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [LEP gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/lep/) (MedlinePlus, US National Library of Medicine, 2026); [LEPR gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/lepr/) (MedlinePlus, US National Library of Medicine, 2026); [Leptin receptor deficiency: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/leptin-receptor-deficiency/) (MedlinePlus, US National Library of Medicine, 2026); [Obesity and overweight](https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight) (World Health Organization, 2026); [LEP: Leptin (human)](https://www.uniprot.org/uniprotkb/P41159/entry) (UniProt, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/topics/leptin-appetite-and-obesity/