{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:12:39Z","timestamp":1789053159825,"version":"build-2803163510"},"reference-count":232,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic condition with a complex pathophysiology involving multiple organs. Organokines, including hepatokines, myokines, cardiokines, renokines, osteokines, and adipokines, play central roles in lipid metabolism, glucose homeostasis, inflammation, and fibrosis. Dysregulation of these signaling molecules contributes to the progression of MASLD and its systemic complications. This review examines the role of organokine-mediated crosstalk between the liver and peripheral organs (e.g., muscle, heart, kidneys, bone, and adipose tissue) in the pathogenesis of MASLD. Key molecules, such as myostatin, FGF-21, IL-6, and adiponectin, influence insulin sensitivity, lipid metabolism, and inflammation. Some organokines have protective effects (e.g., FGF-21, irisin, and klotho), while others, such as myostatin and fetuin-A, exacerbate insulin resistance and fibrosis. These findings suggest that targeting organokines could provide potential biomarkers and therapeutic strategies for MASLD. Future research should focus on elucidating the molecular mechanisms and assessing the role of organokines in the prevention and treatment of MASLD.<\/jats:p>","DOI":"10.3390\/ijms262311547","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T11:19:51Z","timestamp":1764328791000},"page":"11547","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Organokine-Mediated Crosstalk: A Systems Biology Perspective on the Pathogenesis of MASLD\u2014A Narrative Review"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5035-876X","authenticated-orcid":false,"given":"Sandra","family":"Maria Barbalho","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"},{"name":"Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"},{"name":"Department of Biochemistry and Nutrition, School of Food and Technology of Mar\u00edlia (FATEC), Mar\u00edlia 17500-000, SP, Brazil"},{"name":"Department of Research, Research Coordination Center, UNIMAR Charitable Hospital, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"},{"name":"Laboratory for Systematic Investigations of Diseases, Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Fornari","family":"Laurindo","sequence":"additional","affiliation":[{"name":"Division of Cellular Growth, Hemodynamic, and Homeostasis Disorders, Graduate Program in Medical Sciences, Faculdade de Medicina, Universidade de S\u00e3o Paulo (USP), S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7477-3805","authenticated-orcid":false,"given":"Vitor Engracia","family":"Valenti","sequence":"additional","affiliation":[{"name":"Faculty of Philosophy and Sciences, Universidade Estadual Paulista (UNESP), Campus Mar\u00edlia, Mar\u00edlia 17525-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5257-8048","authenticated-orcid":false,"given":"Nahum","family":"M\u00e9ndez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City 14050, Mexico"},{"name":"Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana M.","family":"Ram\u00edrez-Mej\u00eda","sequence":"additional","affiliation":[{"name":"Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City 14050, Mexico"},{"name":"Plan of Combined Studies in Medicine (PECEM-MD\/PhD), Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo de Alvares","family":"Goulart","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102628","DOI":"10.1016\/j.arr.2024.102628","article-title":"Sarcopenia in trauma patients: A systematic review and meta-analysis","volume":"104","author":"Zhang","year":"2024","journal-title":"Ageing Res. 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