Effects of a Bioactive Vegetable-Enriched Diet on Autotaxin and Liver Fibrosis in MASLD with Evidence of Sex-Specific Responses: A Pilot Study

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a frequent manifestation of obesity and other metabolic diseases. Autotaxin (ATX), an enzyme involved in the generation of lysophosphatidic acid (LPA), has recently emerged as a potential biomarker of metabolic inflammation and liver disease progression. Vegetable-based dietary interventions have been shown to reduce liver steatosis, but evidence of the impact of this dietary approach on ATX levels remains limited. Objectives: To evaluate the short-term effects of a bioactive vegetable-enriched diet from the Brassicaceae and Asteraceae families on serum ATX levels and liver-related parameters in individuals with obesity and MASLD, with a specific focus on sex differences. Methods: In this two-month pilot study, 44 obese adults (BMI > 30 kg/m²) underwent clinical and instrumental assessments at baseline (T0) and after the dietary intervention (T1). Results: After the intervention, serum ATX levels significantly decreased (from 206.3 ± 52.8 to 191.7 ± 45.7 ng/mL, p < 0.001), and there were improvements in metabolic parameters (BMI, waist circumference, blood pressure, fat mass, insulin, HOMA-IR, triglycerides, total and LDL cholesterol) and liver indices (CAP, ALT, AST, γGT). The multivariate GEE model confirmed a significant reduction in ATX, independent of age, sex, FFM, LPA, LSM, Hemoglobin A1c, and PAI-1 (β = −9.87, p < 0.001). When stratified by sex, women exhibited a more pronounced reduction in ATX levels (β = −12.24; p = 0.005) compared to men (β = −9.43; p = 0.014). Conclusions: A short-term, vegetable-enriched dietary intervention can significantly reduce serum ATX levels and improve metabolic and liver-related parameters in individuals with MASLD. Sex-specific analysis reveals a greater ATX-lowering effect in women, suggesting potential sex-based differences in ATX metabolism or dietary responsiveness. These findings suggest that ATX may serve as a modifiable biomarker responsive to nutritional intervention and a potential therapeutic target in metabolic liver disease.