What it is
Leptin is a hormone made by fat cells. UniProt's record for human leptin (P41159) gives a 167-residue precursor: a 21-residue signal sequence that steers it out of the cell, then the 146-amino-acid hormone, folded and held by one disulfide bond.
That length matters for a library of peptides. Most definitions put peptides at roughly 2 to 50 amino acids; at 146, leptin is a small protein. It appears here because readers search for it beside the peptide hormones it works with, and because its drug form is one of the reference cases for hormone replacement. The peptide-versus-protein entry sets out where the line falls.
What it does
The gene was found by asking why one strain of mouse, ob/ob, became extremely obese. In 1994 Zhang and colleagues cloned the gene responsible and its human counterpart (Nature, PMID 7984236). The protein it encodes is leptin.
UniProt's function annotation describes leptin as a key regulator of energy balance: released into the blood, it acts on the hypothalamus through the leptin receptor LEPR (UniProt P48357) to reduce food intake and raise energy use, and outside the brain it influences reproduction, insulin secretion, bone mass and immunity. Its partners in appetite control include ghrelin, the stomach's hunger signal, and the melanocortin pathway that setmelanotide targets.
| What is described | How firm |
|---|---|
| Lower food intake, higher energy use | Mouse genetics (1994) and human genetics (1997) |
| Role in reproduction, insulin secretion, bone, immunity | UniProt annotation, partly by similarity to other species |
| Benefit in common obesity | Not shown; not an approved use |
What happens without it
In 1997 Montague and colleagues described two severely obese children from one family whose serum leptin was very low despite their high fat mass. Both carried the same single-guanine deletion in codon 133 of the leptin gene (Nature, PMID 9202122) — the first genetic evidence that leptin controls fat mass in people.
Two years later the same Cambridge group reported one child with congenital leptin deficiency treated with recombinant leptin (New England Journal of Medicine, 1999, PMID 10486419). It is a single case, and is recorded here as that.
The drug form
Metreleptin is recombinant human leptin with one extra methionine at the start — 147 amino acids, about 16.15 kDa, made in E. coli (Myalept label, effective 2024-03-25). FDA licensed it in 2014 (BLA 125390; now held by Chiesi).
Its label is narrow. It is indicated as replacement therapy for the complications of leptin deficiency in congenital or acquired generalised lipodystrophy — a rare condition in which the body has almost no fat tissue. The label states that safety and effectiveness are not established for partial lipodystrophy or for liver disease including NASH, and that it is not indicated for HIV-related lipodystrophy or for metabolic disease without generalised lipodystrophy.
It carries a boxed warning for neutralising anti-metreleptin antibodies, which could block the body's own leptin or the drug's effect, and for T-cell lymphoma, reported in acquired generalised lipodystrophy both with and without treatment. The label's dose table, by body weight and sex, starts at 0.06 mg/kg/day at 40 kg or less, 2.5 mg/day for males above 40 kg and 5 mg/day for females above 40 kg, with a 10 mg/day maximum above 40 kg.
Where it stands
Metreleptin is the only FDA-licensed leptin product (openFDA, 2026-10-04). PubMed returns 47,826 records for leptin, 1,776 tagged as randomised controlled trials. The approved use is replacement where leptin is missing; no FDA-licensed use treats common obesity.
Related reading
For the stomach hormone that pushes the other way, see the hunger hormone ghrelin; for the hormone released with insulin that adds to fullness, see amylin. GLP1 Ledger covers the GLP-1 weight-loss medicines that act on appetite by a different route.