{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:48:01Z","timestamp":1792597681357,"version":"4.5.0"},"reference-count":230,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T00:00:00Z","timestamp":1711411200000},"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-associated fatty liver disease (MAFLD) includes several metabolic dysfunctions caused by dysregulation in the brain\u2013gut\u2013liver axis and, consequently, increases cardiovascular risks and fatty liver dysfunction. In MAFLD, type 2 diabetes mellitus, obesity, and metabolic syndrome are frequently present; these conditions are related to liver lipogenesis and systemic inflammation. This study aimed to review the connection between the brain\u2013gut\u2013liver axis and MAFLD. The inflammatory process, cellular alterations in hepatocytes and stellate cells, hypercaloric diet, and sedentarism aggravate the prognosis of patients with MAFLD. Thus, to understand the modulation of the physiopathology of MAFLD, it is necessary to include the organokines involved in this process (adipokines, myokines, osteokines, and hepatokines) and their clinical relevance to project future perspectives of this condition and bring to light new possibilities in therapeutic approaches. Adipokines are responsible for the activation of distinct cellular signaling in different tissues, such as insulin and pro-inflammatory cytokines, which is important for balancing substances to avoid MAFLD and its progression. Myokines improve the quantity and quality of adipose tissues, contributing to avoiding the development of MAFLD. Finally, hepatokines are decisive in improving or not improving the progression of this disease through the regulation of pro-inflammatory and anti-inflammatory organokines.<\/jats:p>","DOI":"10.3390\/ijms25073694","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T11:34:58Z","timestamp":1711452898000},"page":"3694","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Underlying Mechanisms behind the Brain\u2013Gut\u2013Liver Axis and Metabolic-Associated Fatty Liver Disease (MAFLD): An Update"],"prefix":"10.3390","volume":"25","author":[{"given":"J\u00falia Pauli","family":"De C\u00f3l","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), S\u00e3o Paulo 17525-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enzo Pereira","family":"de Lima","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), S\u00e3o Paulo 17525-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda Moris","family":"Pompeu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), S\u00e3o Paulo 17525-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Cressoni Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), S\u00e3o Paulo 17525-902, Brazil"},{"name":"Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), S\u00e3o Paulo 17525-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"de Alvares Goulart","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), S\u00e3o Paulo 17525-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Dib","family":"Bechara","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), S\u00e3o Paulo 17525-902, Brazil"},{"name":"Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), S\u00e3o Paulo 17525-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3159-0982","authenticated-orcid":false,"given":"Lucas Fornari","family":"Laurindo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Mar\u00edlia (FAMEMA), Mar\u00edlia, S\u00e3o Paulo 17519-080, 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5035-876X","authenticated-orcid":false,"given":"Sandra Maria","family":"Barbalho","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), S\u00e3o Paulo 17525-902, Brazil"},{"name":"Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), S\u00e3o Paulo 17525-902, Brazil"},{"name":"Department of Biochemistry and Nutrition, School of Food and Technology of Mar\u00edlia (FATEC), S\u00e3o Paulo 17500-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s10517-024-06022-1","article-title":"Changes of the Concentration of Short-Chain Fatty Acids in the Intestines of Mice with Different Types of Obesity","volume":"176","author":"Krolenko","year":"2024","journal-title":"Bull. 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