ReviewEndocrine connections2025
Leptin and leptin resistance in obesity: current evidence, mechanisms and future directions.
Review in Endocrine connections, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed.
- Empagliflozin, Linagliptin, and Metformin Differentially Affect Renal PI3K/Akt and MAPK/ERK Signaling Pathways inInternational journal of molecular sciences · 2026Article
- Secretion Patterns of Leptin: A Key Component in the Regulation of Energy Homeostasis and Its Therapeutic Applications.Biomolecules · 2026Review
- Hidradenitis suppurativa: epidemiology, diagnosis, molecular pathogenesis and therapy.Molecular biomedicine · 2026Review
- A Lineup for Next Anti-Obesity Medicines: Beyond Incretin-Based Pharmacotherapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Article
- Peptide Hormones in Appetite Regulation: A Complex Network.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Unravelling obesity: from leptin to glucagon-like peptide-1 receptor agonists.Journal of applied genetics · 2026Review
- Update on Obesity and Its Relationship to Atherosclerotic Cardiovascular Disease and Associated Risk Factors.Journal of clinical medicine · 2026Review
- Chronic attenuation of brain leptin signalling is associated with early metabolic dysfunction in lean rats.The Journal of physiology · 2026Article
- Humanin Restores Metabolic Hormone Homeostasis of Leptin, Ghrelin, Irisin and Asprosin in Streptozotocin-Induced Diabetic Mice.Metabolites · 2026Article
- Adipogenesis Under Leptin Control: Mechanisms and Model-Specific Effects.International journal of molecular sciences · 2026Review
- Non-Pharmaceutical Interventions Based on Diet Restriction and Exercise Improve Morphology and Function of Fatty Pancreas in MaleInternational journal of molecular sciences · 2026Article
- Personalized Medical Nutrition Therapy and Physical Exercise: The Future of Diabesity Care.Current obesity reports · 2026Review
- Leptin Receptor b (LEPRb) Mutations Disrupt Hypothalamic Control of the Reproductive Axis.International journal of molecular sciences · 2026Review
- Obesity and Natural Products: Mechanisms, Therapeutic Potential, and Future Directions.Food science & nutrition · 2026Review
- Adipokine profiles and genetic variants of leptin receptor, adiponectin, and ghrelin pathways in obesity: prospective 12-month outcomes after bariatric interventions.Frontiers in endocrinology · 2026Observational
- Restoring leptin sensitivity in metabolic and extra-metabolic leptin resistance: Pharmacologic strategies, systemic implications, and future directions.EXCLI journal · 2026Review
- Food additives with aldehyde skeleton exhibited leptin resistance in cells.Frontiers in nutrition · 2026Article
- Leptin receptor rs1137101 polymorphism and altered leptin-sOb-R axis contribute to type 2 diabetes risk in Gujarat population.Frontiers in endocrinology · 2026Article
- Indole-3-carbinol ameliorates ER stress-mediated hyperleptinemia in western diet-fed apoEFood & nutrition research · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leptin, a key adipokine regulating energy homeostasis, has been extensively studied for its potential in the management of obesity. However, its therapeutic efficacy is often limited due to leptin resistance. This review synthesizes animal and clinical evidence on leptin's role in obesity, focusing on models such as genetically deficient mice (e.g., ob/ob, db/db), diet-induced obesity mice, and clinical conditions such as congenital leptin deficiency (CLD), leptin receptor deficiency (LRD), lipodystrophy, and common obesity. The mechanisms underlying leptin resistance are summarized, including hyperleptinemia, impaired JAK2-STAT3 signaling, reduced blood-brain barrier permeability, defective autophagy, endoplasmic reticulum stress, inflammation, decreased leptin receptor expression, leptin signaling pathway dysfunction, increased mTOR activity, and peripheral leptin resistance. Due to these leptin receptor and/or post-receptor signaling pathway defects, leptin or its analogs usually fail to produce the expected weight-loss effect in individuals with overweight or obesity, although they remain highly effective in individuals with CLD and lipodystrophy, as well as in ob/ob mice. Alternative strategies, such as melanocortin-4 receptor (MC4R) agonists (e.g., setmelanotide) for LRD treatment, are very promising. Future directions include enhancing leptin sensitization, combining leptin with other drugs, and exploring partial leptin reduction to mitigate compensatory responses during weight loss. The review emphasizes the complexity of leptin resistance and the necessity of targeted approaches in obesity therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.