Page data last changed: . Chemistry registry snapshot: . Registry refreshes and identity assessments are separate from scientific content review.
The hormone that told obesity science it was biology, not willpower — and whose resistance, not absence, defines common obesity.
Also known as: OB protein · obese gene product · LEP · metreleptin (recombinant analogue)
Part of the Foundational & therapeutic peptides cluster
Overview
Leptin is a protein hormone secreted by fat cells that reports the body's energy stores to the brain, reducing food intake and regulating body mass, reproduction and immune function. Cloned in 1994, it was the first single-gene cause of severe obesity identified; its absence is corrected by leptin replacement, but most obesity involves leptin resistance, in which high levels fail to act.
Source & context
Biological / chemical source: Secreted by adipocytes (also placenta and gut); product of the ob (LEP) gene cloned in 1994
Primary research or clinical context: Endogenous hormone; the recombinant analogue metreleptin is used in lipodystrophy, and leptin is investigational in anorexia nervosa
What leptin is
Leptin is an adipocyte-secreted hormone encoded by the ob (LEP) gene, cloned in 1994. Its absence produces severe obesity that is corrected by leptin repletion in both mice and humans, and mutations in leptin or its receptor were the first single-gene mutations found to cause severe obesity (Ahima & Flier, Annual Review of Physiology 2026; Münzberg et al., Metabolism 2024). It regulates food intake, body mass and reproductive function and plays a role in fetal growth, pro-inflammatory immune responses and angiogenesis (Obradovic et al., Frontiers in Endocrinology 2021). Leptin is also synthesised in the placenta and gastrointestinal tract, though its role there is unclear (Prolo et al., International Journal of Biochemistry & Cell Biology 1998).
Mechanism: a starvation signal more than a satiety signal
Leptin's primary role was initially viewed as preventing obesity by rising with fat mass; subsequent research has emphasised the key role of falling levels in signalling starvation (Ahima & Flier, 2026). Circulating leptin varies directly with body mass index and percentage body fat, shows pulsatility and circadian rhythm, and is influenced by metabolic hormones, sex and energy requirements (Prolo et al., 1998). In the central nervous system, leptin acts on neuronal networks that mediate ingestive behaviour, energy balance and reproduction, and the same molecular targets attenuate and terminate the signal — providing the mechanistic basis for leptin resistance (Zhang & Chua, Comprehensive Physiology 2017).
Leptin resistance
Obese people generally have high leptin levels, not low ones, and fail to respond to exogenous hormone, so leptin was abandoned as a general obesity treatment soon after its discovery (Izquierdo et al., Nutrients 2019). Proposed mechanisms include hyperleptinaemia itself, impaired JAK2–STAT3 signalling, reduced blood–brain barrier transport, defective autophagy, endoplasmic reticulum stress, inflammation, reduced receptor expression and increased mTOR activity (Hu et al., Endocrine Connections 2025). A 2025 study proposes a cellular and molecular basis for the resistance seen in diet-induced obese mice, which mirror most humans with obesity (Tan et al., Cell Metabolism 2025).
Where leptin replacement works
Replacement is effective where leptin is genuinely deficient: congenital leptin deficiency, and lipodystrophy, in which fat tissue — and therefore leptin — is lacking (Hu et al., 2025). The recombinant analogue metreleptin is used in that setting; ClinicalTrials.gov lists NIDDK compassionate-use programmes in generalised and partial lipodystrophy (NCT02262832, NCT02262806) and a phase 2 trial of metreleptin in anorexia nervosa (NCT06305182). In total 256 registered studies name leptin as of September 2026, most measuring it as a biomarker rather than giving it.
Leptin and the incretin era
Leptin and GLP-1 both reduce food intake through hypothalamic and hindbrain circuits, but from opposite directions: leptin is a long-term adiposity signal, GLP-1 a meal-timed gut signal. The success of semaglutide and tirzepatide, which work despite leptin resistance, underlines that leptin's signal is blocked rather than absent in common obesity. The semaglutide and GLP-1 profiles on this site cover the incretin side.
What this page is not
Leptin is not sold as a consumer product and “leptin peptides” marketed for weight loss are not leptin. Leptin is a protein hormone of roughly 16 kilodaltons; PubChem's compound record under the name corresponds to a fragment, so this profile does not display a formula or mass. This is an educational profile, not medical advice.
Structure & chemistry
Molecular identity & reference confidence
Reference mass unavailable
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Leptin (source record; form not independently established)
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-09-07
- Receptors
- Leptin receptor (LEPR), signalling through JAK2–STAT3 in hypothalamic and other neurons
- Status
- Endogenous hormone; recombinant metreleptin used in lipodystrophy (compassionate-use and phase 2–3 programmes listed)
- IUPHAR ligand: 5015
Chemistry values: curated profile, IUPHAR/BPS Guide to Pharmacology · fetched 2026-09-07.
Clinical development snapshot
ClinicalTrials.gov lists 258 registered studies with “Leptin” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT07557628 | Study of the Hypothalamic Microglial Response as a Function of a Meal's Lipid Content in Humans. A Single-cent | — | recruiting | 2026-09-29 |
| NCT05888961 | Single-center Prospective Longitudinal Study of Taste in Patients With Cognitive Disorders at Different Stages | Not applicable | recruiting | 2026-09-25 |
| NCT02262806 | Compassionate Use of Metreleptin in Previously Treated People With Partial Lipodystrophy | Phase 2 | active not recruiting | 2026-09-22 |
| NCT07833592 | Targeting the Hepatic BMP-SMAD Pathway in Leptin Receptor Deficiency (LEPRD) | — | recruiting | 2026-09-22 |
| NCT02262832 | Compassionate Use of Metreleptin in Previously Treated People With Generalized Lipodystrophy | Phase 3 | active not recruiting | 2026-09-22 |
| NCT07831733 | Study on the Prevention of Weight Loss Through Physical Activity Among Nursing Home Residents | Not applicable | not yet recruiting | 2026-09-21 |
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- Trials2 registered studies added on ClinicalTrials.gov (now 258).
- IdentifiersCross-linked to IUPHAR ligand 5015.
- TrialsClinicalTrials.gov snapshot added: 256 registered studies, highest phase 4.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Leptin
What is Leptin?+
Leptin is a protein hormone secreted by fat cells that reports the body's energy stores to the brain, reducing food intake and regulating body mass, reproduction and immune function. Cloned in 1994, it was the first single-gene cause of severe obesity identified; its absence is corrected by leptin replacement, but most obesity involves leptin resistance, in which high levels fail to act.
What Canadian product status is recorded for Leptin?+
Canadian product status for Leptin has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Leptin?+
Leptin is not a classic amino-acid chain peptide in the same sense; see the profile for classification details.
What is leptin?+
A protein hormone secreted by fat cells that signals the body's energy stores to the brain, reducing food intake and regulating body weight, reproduction and immune function. It was cloned in 1994.
What is leptin resistance?+
The state, typical of common obesity, in which leptin levels are high but the brain fails to respond. Mechanisms include impaired JAK2–STAT3 signalling, reduced transport into the brain, inflammation and ER stress.
Can leptin be used to treat obesity?+
Only where leptin is genuinely deficient — congenital leptin deficiency and lipodystrophy, where the recombinant analogue metreleptin is used. In common obesity, leptin resistance blocks the effect.
Is leptin a peptide?+
It is a protein hormone — a much longer chain than the peptides in this directory. It is included because of its central role in the biology the metabolic peptides act on.
Related peptides
References & further reading
- 1.Ahima & Flier (2026). Leptin: 30 Years Later. Annual Review of Physiology
- 2.Münzberg et al. (2024). History and future of leptin: Discovery, regulation and signaling. Metabolism
- 3.Obradovic et al. (2021). Leptin and Obesity: Role and Clinical Implication. Frontiers in Endocrinology
- 4.Hu et al. (2025). Leptin and leptin resistance in obesity: current evidence, mechanisms and future directions. Endocrine Connections
- 5.Tan et al. (2025). A cellular and molecular basis of leptin resistance. Cell Metabolism
- 6.Zhang & Chua (2017). Leptin Function and Regulation. Comprehensive Physiology
- 7.Izquierdo et al. (2019). Leptin, Obesity, and Leptin Resistance: Where Are We 25 Years Later? Nutrients