Leptin Deficiency and Monogenic Obesity Mechanisms
Summary
Leptin is a peptide hormone secreted primarily by adipocytes that informs the central nervous system about energy stores and regulates appetite and metabolism. In rare cases, pathogenic variants in the leptin gene (LEP) or its receptor (LEPR) lead to congenital leptin deficiency or resistance, driving severe early-onset obesity through unrelenting hyperphagia and reduced energy expenditure. Monogenic obesity encompasses disorders caused by mutations in single genes that disrupt the leptin–melanocortin pathway, often manifesting with extreme weight gain in infancy, endocrinological abnormalities and heightened susceptibility to infections. Advances in molecular diagnostics have identified multiple biallelic LEP and LEPR mutations, including those yielding bioinactive or antagonistic hormone variants, and have delineated their correlation with clinical severity. The advent of recombinant leptin replacement (metreleptin) and melanocortin-4 receptor agonists offers proof of concept for precision therapy, yet access remains uneven worldwide. Beyond therapeutic avenues, these monogenic models illuminate the broader neuroendocrine control of energy balance, informing our understanding of common polygenic obesity and its interaction with environmental factors.
Research from Nature Portfolio
No recent Nature Portfolio content available.
Leptin Deficiency and Monogenic Obesity Mechanisms publication trend
The graph below shows the total number of articles in leptin deficiency and monogenic obesity mechanisms across all publications each year (not limited to Nature Index journals).
Technical terms
Leptin: A hormone secreted by adipose tissue that signals the status of energy reserves to the hypothalamus, regulating appetite and metabolism.
Monogenic obesity: A form of obesity caused by a mutation in a single gene, often resulting in early-onset, severe weight gain and dysregulated hunger.
Hyperphagia: Excessive eating driven by impaired satiety signalling, characteristic of leptin or leptin receptor deficiencies.
Leptin receptor (LEPR): A transmembrane protein in the hypothalamus that binds leptin, triggering intracellular pathways to suppress appetite and increase energy expenditure.
Metreleptin: A recombinant form of human leptin used as hormone-replacement therapy in patients with congenital leptin deficiency to restore normal appetite control and metabolic function.
References
- High morbidity and mortality in children with untreated congenital deficiency of leptin or its receptor. Cell Reports Medicine (2023).
- Classification of Congenital Leptin Deficiency. The Journal of Clinical Endocrinology & Metabolism (2024).
- Congenital Leptin Deficiency and Leptin Gene Missense Mutation Found in Two Colombian Sisters with Severe Obesity. Genes (2019).
About these summaries
This Nature Research Intelligence Topic summary is created with the cited references and a large language model. We take care to ground generated text with facts, and have systems in place to gain human feedback on the overall quality of the process in line with our AI principles. We strive to create accurate and useful summaries for people unfamiliar with the research topic and that supports this goal. These pages are a beta release and will be updated as we learn how best to help people gain value from a research topic summary.
Turn complex research questions into confident strategic decisions
When you're under pressure to set direction, justify investment, or understand your competitive position, you need more than raw data — you need trusted insights you can act on.
Benchmark your performance against global peers using robust, methodologically sound analysis.
Combine quantitative metrics with qualitative expert insight to uncover strengths, gaps and emerging opportunities.
Gain tailored, decision-ready recommendations aligned to your strategic priorities.
Talk to us to learn more about our data dashboards and bespoke strategy reports.
Grow research skills, confidence and careers with training built for every stage of the research lifecycle.
Developed with Nature Portfolio journal Editors and internationally renowned experts. Discover three ways to learn:
Self-paced, online courses in convenient bite-sized units, covering key skills across scientific writing, publishing, grant writing, data analysis, and more.
Expert trainer-led workshops with hands-on exercises and real-time feedback across core research skills, delivered via interactive group sessions.
Editor-led workshops combining core principles in writing and publishing, personalised 1:1 feedback from Nature Portfolio Editors and hands-on exercises.
Explore course catalogues and workshop agendas, enquire about the options or request institutional pricing.