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Review
. 2025 Jan;13(1):57-68.
doi: 10.1016/S2213-8587(24)00283-3. Epub 2024 Nov 12.

Hypothalamic obesity: from basic mechanisms to clinical perspectives

Affiliations
Review

Hypothalamic obesity: from basic mechanisms to clinical perspectives

Jesús Argente et al. Lancet Diabetes Endocrinol. 2025 Jan.

Erratum in

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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Conflict of interest statement

Declaration of interests JA: received lecture fees from Rhythm Pharmaceuticals, Novo Nordisk, and Sandoz. ISF: received research grants from Rhythm Pharmaceuticals and LG Chem, and received consulting and lecture fees from Rhythm Pharmaceuticals, Eli Lilly, Nodthera Therapeutics, Novo Nordisk, Goldman Sachs, and SV Health. ML: holds an International Patent Cooperation Treated (PCT/EP2022/071463) related to new obesity treatments and is also scientific director of Gazella Biotech. H-WG: subinvestigator in phase 3 clinical trial of setmelanotide (NCT05774756) and received travelling support from Rhythm Pharmaceuticals. HAS: received grants for patient conferences from Novo Nordisk, Pfizer, Sandoz, and Merck; obtained lecture fees from Pfizer; and is founder and chair of the Success Charity, a UK charity advocating for better holistic health outcomes for childhood brain tumour survivors. MW: received consulting and lecture fees from Amryt Pharma, Rhythm Pharmaceuticals, Novo Nordisk, Pfizer, Merck, Nestle, Abbot, Sandoz, InfectoPharm, Mediagnost, and SYNLAB. MT-S: received lecture fees from Novo Nordisk, Sandoz, and IPSEN on topics not related to hypothalamic obesity. The other authors declare no competing interests.

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