Heme oxygenase-1 induction by hemin: a novel approach to enhance mitochondrial turnover and mitigate diet-induced liver damage.

Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by lipid accumulation and inflammatory injury. Kupffer cells (KC) play a key role in the immune response and metabolic homeostasis in the liver. We evaluated the impact of hemin treatment on the phenotype of KC and on metabolism and mitochondrial dynamics of hepatocytes in a rat model of early-stage MASH induced by a high-carbohydrate diet. In the liver, HO-1 induction by hemin was associated with reduced tissue injury and apoptosis, restored oxidative balance, attenuated UPR activation, reinstated autophagic flux and improved mitochondrial dynamics. In addition, hemin treatment enhanced fatty acid oxidation and insulin sensitivity in a KC-independent manner. These results suggest that hemin treatment exerts hepatoprotective effects in a rat model of early-stage MASH, highlighting the potential of this treatment as a therapeutic approach for MASH.