Given the paradoxical impact of TSP1 in liver fat accumulation, we reexamined our global metabolomics study focusing on WT and Thbs1−/− mice fed a low-fat and a high-fat diet to further understand the role of this matricellular protein in liver metabolism and its potential implications in liver injury and diseases such as NAFLD/NASH. The gene discussed is THBS1; the disease is metabolic dysfunction-associated steatohepatitis.