Leptin
Also known as: satiety hormone, ob protein
A 146-amino-acid protein secreted by adipocytes in proportion to fat stores that signals energy sufficiency to the hypothalamus, reducing appetite and permitting energy-expensive processes such as reproduction.
Overview
Leptin, the product of the LEP (ob) gene, established adipose tissue as an endocrine organ. Its plasma concentration is roughly proportional to body fat mass (higher in subcutaneous fat and in women) and falls sharply within days of fasting, before fat mass changes. It crosses into the hypothalamus and binds the long-form leptin receptor (LepRb), a cytokine-family receptor signalling through JAK2–STAT3. In the arcuate nucleus it stimulates POMC/CART neurons (α-MSH → MC4R → satiety) and inhibits NPY/AgRP neurons, reducing food intake and increasing energy expenditure.
Leptin is better understood as a starvation signal than an anti-obesity hormone: a fall in leptin triggers hunger, reduced thyroid and gonadal axis activity (hypothalamic amenorrhoea), reduced energy expenditure and immune suppression. Most obese people have high leptin with leptin resistance (impaired transport and receptor signalling), so leptin treatment does not help common obesity.
- Location
Source: white adipocytes (also placenta, stomach). Targets: arcuate nucleus and other hypothalamic nuclei; GnRH network; immune cells; β cells.
Function
- Signals adequate energy stores; suppresses appetite.
- Increases energy expenditure and sympathetic tone.
- Permits puberty and fertility (via kisspeptin/GnRH).
- Modulates immunity, bone and the thyroid axis.
- Physiology
Class: protein (146 aa, cytokine-like). Receptor: LepRb — JAK2/STAT3.
- Regulation
Increased by fat mass, overfeeding, insulin and glucocorticoids; decreased by fasting, weight loss, catecholamines and cold.
Clinical significance
Congenital leptin deficiency and lipodystrophy
Rare LEP mutations cause extreme early-onset obesity, hyperphagia and hypogonadotropic hypogonadism, reversed by recombinant leptin (metreleptin), which is also used in generalised lipodystrophy (severe insulin resistance, fatty liver).
Low leptin states
Anorexia nervosa and excessive exercise lower leptin, contributing to amenorrhoea, low T3 and bone loss.
Compiled from standard anatomy and physiology references — see the Endocrine System sources. For education only; not medical advice.