Metabolomic analysis reveals novel functions of tomato oleoresin supplementation in the liver of rats with diet-induced metabolic syndrome

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a hepatic manifestation of metabolic syndrome and represents a major public health concern. Lycopene, a potent dietary antioxidant, has been proposed as a hepatoprotective compound; However, its effects on hepatic metabolism in MASLD are not fully understood. This study applied non-targeted metabolomics to evaluate the impact of lycopene supplementation, offered through tomato oleoresin, on liver metabolic alterations induced by a high sugar-fat diet in Wistar rats. After diet-induced metabolic dysfunction, rats received lycopene supplementation provided as tomato oleoresin (10 mg/kg/day) or vehicle for 10 weeks, followed by hepatic non-targeted metabolomic analysis. Supplementation with tomato oleoresin improved systemic metabolic parameters, including reduced plasma triglycerides (19.5%) and increased HDL-cholesterol (52.6%), and significantly attenuated hepatic triglyceride accumulation (11.9%). Hepatic metabolomic profiling revealed that MASLD induced marked disruptions in amino acid and lipid metabolism, whereas tomato oleoresin supplementation partially reversed these alterations. Notably, this intervention increased hepatic levels of branched-chain amino acids D-Leucine (36.4%), L-leucine (29.0%) and L-isoleucine (28.4%) and sphinganine-1-phosphate (22.6%), metabolites involved in energy metabolism, lipid handling, and cellular signaling. These findings link improvements in systemic metabolic markers to specific hepatic metabolic pathways and provide mechanistic insights into the hepatoprotective effects of tomato oleoresin, supporting a central role for lycopene in MASLD management. Tomato oleoresin supplementation reduced liver triglyceride accumulation in MetS. Lycopene restored hepatic levels of key branched-chain amino acids. The study unveils novel metabolic pathways influenced by lycopene in the liver. Findings indicate lycopene’s potential in MetS-related liver disorders management.