Leptin

Where it comes from

Made in

White fat cells, in proportion to their fat content; also placenta and stomach

Sent out by

Steady, with a night-time rise; falls fast with fasting, long before fat is lost

Acts on

• Hypothalamus (arcuate nucleus: NPY/AgRP and POMC neurons)
• Brainstem
• Immune cells
• Reproductive axis

What it does

• Tells the brain the body is fed: it suppresses hunger and allows puberty, fertility and thyroid output
• Its fall in starvation is the signal that shuts those down
• High in obesity, where the brain stops responding (leptin resistance); it was found by positional cloning of the mouse obese gene in 1994 ¹

In medicine

• Metreleptin, recombinant leptin, has been approved since 2014 for generalised lipodystrophy, where there is almost no fat and so almost no leptin ²
• Children with congenital leptin deficiency, a very rare condition, lose their extreme obesity on it, and their hunger falls within days ⁴
• In ordinary obesity leptin injections disappointed: a 1999 trial found modest, highly variable weight loss that rose with dose, and the use was not pursued ³

Beyond the body’s own use

• Leptin is studied to prevent weight regain after dieting, when its level drops, and small trials have restored periods in hypothalamic amenorrhoea; neither is an approved use
• Claims for “leptin supplements” rest on nothing: leptin is a protein and is digested when swallowed, and no leptin product is approved for ordinary weight loss ³