A Whole Tomato Food Supplement Modulating Lipidomic and Proteomic Profiles in HepG2 Cells as a Dietary Tool for the Management of Non-Alcoholic Fatty Liver Disease

Background: The increasing consumption of the western diet, rich in highly refined fats and carbohydrates, is becoming the primary culprit of dietary hepatic lipid accumulation in adults and youngsters This storage, if uncontrolled, induces hepatocyte cell death and sustains inflammation and fibrosis, which are responsible for the increasing prevalence of non-alcoholic fatty liver disease (NAFLD), the gate to cirrhosis and cancer. Due to a lack of targeted therapies, dietary regimens rich in functional foods by providing complexes of antioxidants may be therapeutically advantageous. Objective: Lycopene supplementation and tomato-rich diets are under scrutiny since they have shown promising clinical outcomes with no toxicities, large availability at contained costs. In the present report we have investigated whether a novel whole tomato-based food supplement (WTFS), endowed with potent antioxidant activity and capable of interfering with multiple metabolic pathways, can modulate mechanisms fostering the progression of NAFLD. Methods: Lipidomic assays and proteomic analysis were performed in the HepG2 human cell line, treated with WTSF. Results: WTFS induces a marked reduction in triglyceride and cholesterol ester content, a decrease in the relative levels of diacylglycerols, lysophosphatidylcholine, lysophosphatidylethanolamines, phosphatidylethanolamines, and decreased expression of transforming growth factor-α, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), and Fms-related tyrosine kinase 3 ligand (FLT3LG), modulating signaling relevant to NAFLD progression. Conclusions: WTFS may represent a potential candidate for clinical trials in supplementing the hard-to-follow Mediterranean diet, the presently first-line preventive and therapeutic dietary option for NAFLD.