{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T12:11:09Z","timestamp":1781179869174,"version":"3.54.1"},"reference-count":34,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health Ricerca Corrente 2025","award":["DDG 851\/23"],"award-info":[{"award-number":["DDG 851\/23"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver condition intricately linked to systemic metabolic impairments. Among the molecular mediators implicated in its pathogenesis, follistatin and plasminogen activator inhibitor-1 (PAI-1) play a significant role in inflammatory, fibrotic, and metabolic processes. However, the interplay between these two biomarkers in the context of MASLD remains poorly understood. Objective: This study analyzes the relationship between follistatin and PAI-1 in subjects with MASLD and obesity. It also assesses changes in these biomarkers and metabolic parameters after a dietary intervention that involves increasing one serving of vegetables and reducing one serving of carbohydrates. Methods: Forty-four individuals with MASLD and obesity participated in a two-month dietary intervention. The concentrations of PAI-1 and follistatin were measured at baseline and post-intervention. Multivariate linear regression models, adjusted for age, gender, waist circumference, and insulin resistance (measured by HOMA-IR), were employed to analyze the association between the two biomarkers. Results: Following the dietary intervention, PAI-1 levels showed a significant reduction (from 35.76 to 33.54 ng\/mL; p &lt; 0.001), whereas follistatin concentrations remained relatively stable (from 43.6 to 45.3 ng\/mL; p = 0.392). Post-intervention, multivariate analysis reveals that higher follistatin levels were independently associated with lower PAI-1 levels. The inclusion of follistatin in the regression model enhanced the estimated dietary effect on PAI-1 reduction (from \u20130.145 to \u20130.194), suggesting a possible independent modulatory role of follistatin in the regulation of PAI-1 levels. Conclusions: These findings indicate that follistatin may act as an inhibitory regulator of PAI-1 expression in individuals with MASLD and obesity, potentially contributing to reductions in the prothrombotic status during dietary intervention. The data suggest a synergistic relationship between follistatin and PAI-1 in the regulation of prothrombotic status in conditions of hepatic steatosis.<\/jats:p>","DOI":"10.3390\/nu17132124","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T11:15:23Z","timestamp":1750936523000},"page":"2124","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Association Between Follistatin and PAI-1 Levels in MASLD Subjects Undergoing a Plant-Based Dietary Intervention"],"prefix":"10.3390","volume":"17","author":[{"given":"Nicole","family":"Cerabino","sequence":"first","affiliation":[{"name":"Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d, Castellana Grotte, 70013 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8650-348X","authenticated-orcid":false,"given":"Caterina","family":"Bonfiglio","sequence":"additional","affiliation":[{"name":"Unit of Data Science, National Institute of Gastroenterology \u201cSaverio de Bellis\u201d, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2759-8347","authenticated-orcid":false,"given":"Martina","family":"Di Chito","sequence":"additional","affiliation":[{"name":"Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d, Castellana Grotte, 70013 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Donvito","sequence":"additional","affiliation":[{"name":"Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d, Castellana Grotte, 70013 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Pio","family":"Mongelli","sequence":"additional","affiliation":[{"name":"Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d, Castellana Grotte, 70013 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4675-2075","authenticated-orcid":false,"given":"Pasqua Letizia","family":"Pesole","sequence":"additional","affiliation":[{"name":"Core Facility Biobank, National Institute of Gastroenterology \u201cSaverio de Bellis\u201d, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores","family":"Stabile","sequence":"additional","affiliation":[{"name":"Core Facility Biobank, National Institute of Gastroenterology \u201cSaverio de Bellis\u201d, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4909-0436","authenticated-orcid":false,"given":"Endrit","family":"Shahini","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, National Institute of Gastroenterology \u201cSaverio de Bellis\u201d, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Zappimbulso","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, National Institute of Gastroenterology \u201cSaverio de Bellis\u201d, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Cozzolongo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, National Institute of Gastroenterology \u201cSaverio de Bellis\u201d, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5140-8060","authenticated-orcid":false,"given":"Gianluigi","family":"Giannelli","sequence":"additional","affiliation":[{"name":"Scientific Direction, National Institute of Gastroenterology \u201cSaverio de Bellis\u201d, IRCCS Hospital, Castellana Grotte, 70013 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0020-3273","authenticated-orcid":false,"given":"Giovanni","family":"De Pergola","sequence":"additional","affiliation":[{"name":"Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d, Castellana Grotte, 70013 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1053\/j.gastro.2019.11.312","article-title":"International Consensus Panel. 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