PTEN and steatosis: In BRUCE-KO mice, preserved PTEN activity limits lipogenesis resulting in mild MASLD from impaired FAO alone, or the ‘first hit.’ However, in DKO mice, failed lipid oxidation (BRUCE loss) combined with the ‘second hit’ of unrestrained DNL (PTEN loss) creates a metabolic vicious cycle, explaining both the initial steatosis in BKO and its dramatic exacerbation in DKO.