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
- Metabolic syndrome
- Type 2 diabetes mellitus
- Obstructive sleep apnoea
- Polycystic ovary syndrome
- Marasmus
Related
- JAK–STAT pathway
- Insulin signalling
- Fed, fasting and starvation states
- Aromatase (CYP19A1)
- AMP-activated protein kinase (AMPK)
- mTOR (mechanistic target of rapamycin)
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.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: LEP gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); LEPR gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Leptin receptor deficiency: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Obesity and overweight (World Health Organization, 2026); LEP: Leptin (human) (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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Representative model, for educational purposes only.