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Association Between Follistatin and PAI-1 Levels in MASLD Subjects Undergoing a Plant-Based Dietary Intervention

Study · human · Nutrients · 2025 · DOI 10.3390/nu17132124 · PMID 40647228

Plain-language summary

Paraphrased from the published abstract below — not a verdict on whether anything works.

This study examined Forty-four human individuals with MASLD and obesity in a two-month dietary intervention (adding one vegetable serving, reducing one carbohydrate serving), measuring follistatin and PAI-1 at baseline and post-intervention. PAI-1 levels decreased after the intervention (from 35.76 to 33.54 ng/mL; p < 0.001), while follistatin concentrations remained relatively stable (from 43.6 to 45.3 ng/mL; p = 0.392). Post-intervention, higher follistatin levels were independently associated with lower PAI-1 levels, and including follistatin in the regression model changed the estimated dietary effect on PAI-1 reduction from -0.145 to -0.194. The authors describe this as suggesting follistatin may act as a regulator of PAI-1 expression and a modulator of prothrombotic status during dietary intervention in MASLD and obesity.

Abstract

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 < 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 -0.145 to -0.194), 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.

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