Leptin (LEP)
Leptin is a 16 kDa adipokine encoded by the LEP gene and secreted mainly by white adipose tissue in proportion to fat mass, making it the body's signal of stored energy.
Leptin is a 16 kDa adipokine encoded by the LEP gene and secreted mainly by white adipose tissue in proportion to fat mass, making it the body's signal of stored energy. It acts through the leptin receptor (LEP-R) in the hypothalamic arcuate nucleus, stimulating anorexigenic POMC neurons and inhibiting orexigenic AgRP/NPY neurons to suppress food intake and permit energy expenditure. The receptor is a class I cytokine receptor with no intrinsic catalytic activity: ligand binding brings together receptor chains whose associated JAK2 molecules trans-phosphorylate each other and then the receptor tail, recruiting and activating signal transducer and activator of transcription 3 (STAT3), with Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (PKB) and AMPK cascades alongside. Its own feedback inhibitors, SOCS3 and the phosphatase PTP1B, terminate the signal — and are also implicated in blunting it chronically. That is the paradox of the hormone: people with obesity have high circulating leptin yet behave as though they have none, a resistance attributed to saturable transport across the blood–brain barrier and to attenuated receptor signaling centrally, and one that intersects with insulin, glucagon-like peptide-1 (GLP-1) and AMPK pathways.
Leptin's discovery raised the expectation that giving it would treat obesity, and the outcome defines the field: recombinant leptin corrects the severe hyperphagia and obesity of congenital leptin deficiency almost completely, and is approved for generalized lipodystrophy, where fat tissue and therefore leptin are absent — but it does little in common obesity, where the hormone is already abundant. Leptin is better understood as a starvation signal than a satiety one, since falling levels defend body weight far more forcefully than rising levels restrain it, which is also why the fall in leptin after weight loss drives the compensatory hunger that follows.
Beyond metabolism, leptin has pleiotropic effects in reproduction — where it permits puberty and fertility only when energy stores suffice — and in immune modulation, bone metabolism, cardiovascular regulation and oncology. It shapes inflammatory cytokine networks, interacting with Interleukin-6 (IL-6) and C-reactive protein (CRP), and modulates coagulation. In placental biology, LEP expression serves as a marker of trophoblast function and metabolic adaptation in pregnancy. Leptin resistance, frequently co-occurring with insulin resistance and type 2 diabetes, is a central feature of obesity-related metabolic dysfunction.
Where the papers sit
10 papers from the last 6 months study Leptin (LEP) directly · updated from PubMed 11 Oct 2026
Study type 2 clinical trials · 3 observational · 1 human data · 4 preclinical
Themes 3 themes · 1 new direction
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Obesity and Leptin Resistance
Obesity research is moving toward combined metabolic interventions that restore leptin responsiveness and improve lipid handling. FGF21 is paired with leptin to address hepatic leptin resistance, while LEP/AMPK/ACC modulation and intestinal effects are explored in diet-induced obesity. Aerobic exercise, hypocaloric diets, and tirzepatide-related biomarker work broaden treatment beyond leptin alone. Waist-hip ratio, body roundness, Adiponectin (APN), and serum leptin remain recurring markers of cardiometabolic risk.
4 papers · 40%
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Placental Adipokine Biology
Placental adipokine expression is being linked to maternal metabolic stress and pregnancy outcomes. Leptin and Adiponectin (APN) recur in studies of hyperketonemia, gestational diabetes, and pregnancies after bariatric surgery. Transcriptomic and immune differences are being used to connect altered placental metabolism with maternal cardiac and fetal health. The evidence remains observational and does not establish a common causal pathway.
3 papers · 30%
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Others — Inflammation, Immunity and Metabolism
Leptin is linked separately to inflammatory coagulation in severe COVID-19, immune activation in oncolytic viral therapy, and cardiometabolic biomarker changes during tirzepatide treatment. Interleukin-6, C-C motif chemokine ligand 2, fibrinogen, and T-cell responses recur across parts of the cluster. These applications do not converge on one disease mechanism or therapeutic direction. The group is therefore best treated as unrelated inflammatory, immunologic, and metabolic studies.
3 papers · 30%
Leptin functions as an oncolytic viral immunotherapy payload that enhances antitumor memory T-cell responses
The ASP1012 engineered vaccinia-virus model for multiple mouse tumors uses a Leptin–IL-2 fusion protein, rather than treating leptin as a metabolic adipokine or disease biomarker, to remodel the tumor microenvironment and strengthen systemic antitumor immunity, producing complete responses after intravenous delivery; this extends leptin into an active component of cancer immunotherapy 42421317Jul.
Papers
The 10 papers from the last 6 months that study Leptin (LEP) directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
Obesity and Leptin Resistance (4)
- Growth differentiation factor-15 and body roundness index in relation to cardiometabolic risk in young adults with obesity. Endocrine · 16 Sept 2026 PMID 42747598
- Heyehui attenuates diet-induced obesity via regulating LEP/AMPK/ACC axis and restoring intestinal function in mice. Phytomedicine : international journal of phytotherapy and phytopharmacology · 17 Jul 2026 PMID 42468370
- FGF21 synergizes with leptin to counteract obesity-related metabolic comorbidities by reversing hepatic leptin resistance. Cell metabolism · 16 Jul 2026 PMID 42462724
- Aerobic Exercise Plus Hypocaloric Diet on Serum Leptin Concentrations in Adults With Primary Hypertension and Overweight/Obesity: Results From the EXERDIET-HTA Trial. Clinical obesity · 4 May 2026 PMID 42082343
Placental Adipokine Biology (3)
- Gene expression of adipokines in placentas of cows from Northeastern Brazil with and without hyperketonemia and their interactions with metabolic biomarkers. Tropical animal health and production · 10 Aug 2026 PMID 42573864
- Role of Adipokines in Maternal Cardiac Function of Pregnancies Following Metabolic Bariatric Surgery. Obesity surgery · 4 Jun 2026 PMID 42240794
- Placental transcriptome profiling and immune signature differences in pregnancies with and without gestational diabetes mellitus: An observational study. Medicine · 23 May 2026 PMID 42175401
Others — Inflammation, Immunity and Metabolism (3)
- The oncolytic viral immunotherapy ASP1012 optimizes memory T cell responses after systemic delivery. Molecular therapy : the journal of the American Society of Gene Therapy · 9 Jul 2026 PMID 42421317
- Comprehensive Long-Term Changes in Cardiovascular Risk Biomarkers With Tirzepatide: A SURMOUNT-1 Post Hoc Analysis. Journal of the American College of Cardiology · 3 Jun 2026 PMID 42233927
- Cross-talk between inflammation and coagulation in severe COVID-19: Association of leptin and classical pro-inflammatory markers with coagulation disorders in a single-center observational cohort study. Medicine · 1 May 2026 PMID 42065184
By study type
Clinical trials (2)
- Comprehensive Long-Term Changes in Cardiovascular Risk Biomarkers With Tirzepatide: A SURMOUNT-1 Post Hoc Analysis. Journal of the American College of Cardiology · 3 Jun 2026 PMID 42233927
- Aerobic Exercise Plus Hypocaloric Diet on Serum Leptin Concentrations in Adults With Primary Hypertension and Overweight/Obesity: Results From the EXERDIET-HTA Trial. Clinical obesity · 4 May 2026 PMID 42082343
Observational studies and case reports (3)
- Growth differentiation factor-15 and body roundness index in relation to cardiometabolic risk in young adults with obesity. Endocrine · 16 Sept 2026 PMID 42747598
- Placental transcriptome profiling and immune signature differences in pregnancies with and without gestational diabetes mellitus: An observational study. Medicine · 23 May 2026 PMID 42175401
- Cross-talk between inflammation and coagulation in severe COVID-19: Association of leptin and classical pro-inflammatory markers with coagulation disorders in a single-center observational cohort study. Medicine · 1 May 2026 PMID 42065184
Human data, design not indexed (1)
- Role of Adipokines in Maternal Cardiac Function of Pregnancies Following Metabolic Bariatric Surgery. Obesity surgery · 4 Jun 2026 PMID 42240794
Preclinical: animal, cell and lab studies (4)
- Gene expression of adipokines in placentas of cows from Northeastern Brazil with and without hyperketonemia and their interactions with metabolic biomarkers. Tropical animal health and production · 10 Aug 2026 PMID 42573864
- Heyehui attenuates diet-induced obesity via regulating LEP/AMPK/ACC axis and restoring intestinal function in mice. Phytomedicine : international journal of phytotherapy and phytopharmacology · 17 Jul 2026 PMID 42468370
- FGF21 synergizes with leptin to counteract obesity-related metabolic comorbidities by reversing hepatic leptin resistance. Cell metabolism · 16 Jul 2026 PMID 42462724
- The oncolytic viral immunotherapy ASP1012 optimizes memory T cell responses after systemic delivery. Molecular therapy : the journal of the American Society of Gene Therapy · 9 Jul 2026 PMID 42421317
Written from 10 PubMed abstracts, each one listed by PMID above. Published: 2026-06-16. Last written: 2026-09-18 by GPT. Corrections: 2026-08-08 by GPT. Drafted by language models from published abstracts; not medical advice.