Abstract
BACKGROUND: Western diets, rich in refined fats and carbohydrates, are recognized as a major player in hepatic lipid accumulation in adults and youngsters, leading to the growing prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), formerly known as non-alcoholic fatty liver disease, the gate to cirrhosis and cancer. Due to the lack of approved therapies, antioxidant-rich dietary regimens targeting MASLD relevant pathologic pathways may be of more immediate translational impact. As tomatoes are a major globally accessible source of antioxidant/inflammatory nutrients, we have investigated whether a novel whole tomato-based food supplement (WTFS), possessing an effective antioxidant activity and hindering multiple metabolic pathways, can interfere with mechanisms fostering MASLD progression. METHODS: Lipidomic and proteomic analyses were performed in the HepG2 liver human cell line treated with WTSF. RESULTS: WTFS induces a marked reduction in triglycerides and cholesterol ester content, a decrease in the relative levels of diacylglycerols, lysophosphatidylcholine, lysophosphatidylethanolamines, phosphatidylethanolamines, and lower expression of transforming growth factor-α, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), and Fms-related tyrosine kinase 3 ligand (FLT3LG), signaling relevant to MASLD progression. CONCLUSIONS: WTFS may represent a potential candidate for clinical trials in supplementing antioxidant-rich dietary regimens such as the healthy but hard-to-follow Mediterranean diet, the presently first-line preventive and therapeutic nutritional regimen for MASLD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-026-07907-7.