Hypothalamic obesity: from basic mechanisms to clinical perspectives
Abstract
Despite the diverse nature of obesity, there is compelling genetic, clinical, and experimental evidence that endorses the important contribution of brain circuits to this condition. The hypothalamus contains major regulatory circuits for bodyweight homoeostasis, the deregulation of which can lead to obesity. Although functional perturbation of hypothalamic pathways could lie at the basis of common forms of obesity, the term hypothalamic obesity has been created to define those rare forms of severe obesity where a clear hypothalamic substrate can be identified, either of genetic or acquired origin. An in-depth understanding of the pathogenesis, clinical presentation, and therapeutic targets of hypothalamic obesity relies on the comprehension of the physiological basis of hypothalamic pathways governing bodyweight control, the mechanisms (either genetic or acquired) whereby they are perturbed, and the consequences of such perturbation. In this Review, we provide a synoptic overview of hypothalamic obesity, from basic mechanisms to clinical perspectives, with a major focus on current developments and new avenues for the diagnosis and precise treatment of these rare forms of obesity.
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Healthful nutrition and physical activity are rarely sufficient to address weight gain in hypothalamic obesity.
“but are rarely sufficient to address weight gain”
From Approach to the patient with acquired hypothalamic syndrome (2026) · cites this paper as [37]
Healthful nutrition and physical activity, as well as other aspects of lifestyle modification, are critical aspects of treatment, especially to prevent or mitigate obesity-related health problems.
“Healthful nutrition and physical activity, as well as other aspects of lifestyle modification, are critical aspects of treatment, especially to prevent or mitigate obesity-related health problems”
From Approach to the patient with acquired hypothalamic syndrome (2026) · cites this paper as [37]
Pharmacotherapy is playing an increasing role in the treatment of hypothalamic obesity.
“as a result, pharmacotherapy is playing an increasing role (36, 37)”
From Approach to the patient with acquired hypothalamic syndrome (2026) · cites this paper as [37]
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Approach to the patient with acquired hypothalamic syndrome
Grishman, E. K., & McCormack, S. E. (2026) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgag197
- Authors
- Argente, J., Farooqi, I. S., Chowen, J. A., Kühnen, P., López, M., Morselli, E., Gan, H.-W., Spoudeas, H. A., Wabitsch, M., & Tena-Sempere, M.
- Affiliations
- Madrid Institute for Advanced Studies (ES)
- University of Cambridge (GB)
- Charité – Universitätsmedizin Berlin (DE)
- Universidade de Santiago de Compostela (ES)
- Universidad San Sebastián (CL)
- Great Ormond Street Hospital for Children NHS Foundation Trust (GB)
- University Hospital Ulm (DE)
- Corresponding author
- Argente, Jesús
- ORCID
- Venue
- The Lancet Diabetes & Endocrinology
- Publisher
- Elsevier BV
- Published
- 2025-01
- Volume
- 13
- Issue
- 1
- Pages
- 57-68
- ISSN
- 2213-8587 (ISSN-L)
- OpenAlex
- W4404283407
- Cited by
- 57
- References
- 10
- Citations by year
- 2026: 46 · 2025: 11
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Update notices
- erratum (2025-01-01)
- Open access
- closed
- Licence
- Locations
- The Lancet Diabetes & Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fondo Nacional de Desarrollo Científico y Tecnológico (1240623, 01GL2407A)
- Wellcome Trust (207462/Z/17/Z)
- Agencia Estatal de Investigación (PID2021\u2013122653OB-I00, PID2020\u2013118660GB-I00, PID2021\u2013128145NB-I00)
- Bundesministerium für Bildung und Forschung (GAP-101080219)
- BMBF Berlin
- Federación Española de Enfermedades Raras
- Instituto de Salud Carlos III (FIS-PI19/00166)
- HORIZON EUROPE Framework Programme
- European Commission
- Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Keywords
- hypothalamic obesity, hypothalamus, body weight homeostasis, hypothalamic pathways, genetic obesity, obesity pathogenesis, obesity treatment, obesity diagnosis
- MeSH terms
- Animals, Humans, Hypothalamic Diseases, Hypothalamus, Obesity
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