{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T16:30:54Z","timestamp":1791649854690,"version":"4.3.4"},"reference-count":193,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T00:00:00Z","timestamp":1763769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Union NextGenerationEU"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Depression is a leading cause of global disability and is increasingly recognized as a multifactorial disorder characterized by fundamental disruptions in neuroplasticity, including diminished hippocampal neurogenesis, impaired synaptic plasticity, and dysregulated stress-response systems. Given the limited efficacy of conventional pharmacological treatments, lifestyle-based interventions\u2014most notably physical exercise\u2014have gained considerable attention for their antidepressant effects, partly mediated by secreted exerkines. Among these, adiponectin has emerged as a particularly compelling candidate linking metabolic regulation to neuroplasticity and mood. Recent evidence suggests that adiponectin contributes to the antidepressant effects of exercise by modulating hippocampal neurogenesis, neuroinflammation, and brain-derived neurotrophic factor (BDNF) signalling. Despite these advances, the mechanisms by which adiponectin influences depression remain incompletely understood. This review synthesizes current knowledge on adiponectin\u2019s role in depression pathophysiology, with emphasis on its capacity to enhance neuroplasticity and hippocampal neurogenesis, and its potential to mediate exercise-induced antidepressant effects via defined molecular pathways. Building on these insights, we discuss adiponectin\u2019s translational promise as both a predictive biomarker of treatment response and a novel therapeutic target. By integrating preclinical and clinical evidence, this review offers a comprehensive perspective on adiponectin\u2019s involvement in depression while identifying critical gaps to guide future mechanistic research.<\/jats:p>","DOI":"10.3390\/biom15121642","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T10:24:17Z","timestamp":1763979857000},"page":"1642","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["From Fat to Brain: Adiponectin as a Mediator of Neuroplasticity in Depression"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1238-5440","authenticated-orcid":false,"given":"Patrizia","family":"Genini","sequence":"first","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy"},{"name":"Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilari","family":"D\u2019Aprile","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9517-2291","authenticated-orcid":false,"given":"Giulia","family":"Petrillo","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3165-0044","authenticated-orcid":false,"given":"Maria Grazia","family":"Di Benedetto","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Begni","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Cattane","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9963-848X","authenticated-orcid":false,"given":"Annamaria","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy"},{"name":"Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1038\/s41380-022-01520-y","article-title":"Dysregulation of Adult Hippocampal Neuroplasticity in Major Depression: Pathogenesis and Therapeutic Implications","volume":"27","author":"Tartt","year":"2022","journal-title":"Mol. 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