Looking for potential molecular drivers of the enhanced steatosis and fibrosis developed by NASH‐HCC‐Spp1−/− mice, we performed targeted lipidomic analyses with emphasis on diacylglycerols (DAGs) and ceramides (CERs) of livers at the NAFL/NASH time point. This evidence concerns the gene SPP1 and metabolic dysfunction-associated steatohepatitis.