Ferreira, VitorFernández González, IaraVattathara, Jane JoseRodríguez Díaz, AmandaFernández Sanmartín, PaolaDiéguez González, Carlos2026-04-222026-04-222026-03-19https://hdl.handle.net/10347/46879Closely associated with the exponential increase of obesity and sedentary life, liver-related disorders are a major global health concern. Recent data suggest that the global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) among adults is of 32% and 5.1% for alcohol-related liver disease, with hepatic disorders contributing to 4% of global mortality, accounting for approximately 2 million deaths annually. Over the past two decades, the hypothalamus has emerged as a central hub in regulating whole body metabolic and energy homeostasis. Nevertheless, the interactome between the hypothalamus and the liver in the progression of liver metabolic dysfunctions, as well as its potential as a therapeutic target, remains poorly understood. In this review, we provide a comprehensive overview of the current knowledge regarding the hypothalamus-liver crosstalk, with a particular emphasis on the mechanisms underlying it. We explore how signals transmitted by different hormones can modulate these interactions, shedding light on their functional implications for hepatic regulation and systemic homeostasis through central signals.engThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/HypothalamusLiver diseaseObesityDiabetesInsulinAmylinGlucagonGLP-1FGF21journal article10.1007/s11154-026-10031-y1573-2606open access