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 31 papers.
What it found
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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
31 citing papers in PubMed.
- Adipokines as Regulators of Nitric Oxide Synthase Isoforms Across Organs: Emerging Implications for Gastrointestinal Motility.International journal of molecular sciences · 2026Review
- Phytochemicals and Irisin as Multi-Target Regulators of Adipose Tissue Browning and Metabolic Reprogramming: Synergies with GLP-1 Pathways.Antioxidants (Basel, Switzerland) · 2026Review
- Hyperglycemia associated brain dysfunction: rodent models for studying diabetic cognitive deficits.Metabolic brain disease · 2026Review
- Diet-Dependent Effects of Intracerebroventricular Maresin-1 on Hypothalamus of Rats.International journal of molecular sciences · 2026Article
- Global Research Landscape on Leptin Resistance and Obesity-Related Metabolic Dysfunction: Trends, Networks and Visualisation Analysis (1995-2025).Endocrinology, diabetes & metabolism · 2026Review
- Remodeling the Immune Landscape: How Obesity-Induced SASPs Create a Pro-Tumorigenic Niche.Current obesity reports · 2026Review
- Beyond Obesity: Sex-Specific Associations of Vaspin with Metabolic Dysfunction.Journal of clinical medicine · 2026Article
- Sulforaphane and Broccoli-Derived Preparations in Obesity and Obesity-Related Metabolic Dysfunction: Mechanistic Insights, Preclinical Evidence, and Clinical Perspectives.Pharmaceuticals (Basel, Switzerland) · 2026Review
- 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
Corrections and comments
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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 OpenQuestion graph.