Histone lactylation: A key epigenetic modulator in the pathogenesis of metabolic dysfunction-associated steatohepatitis and alcoholic steatohepatitis

Figure 2 Role of histone lactylation in metabolic dysfunction-associated steatohepatitis pathogenesis. Preclinical models of metabolic dysfunction-associated steatohepatitis (MASH) have shown increased cellular plasticity in response to histone lactylation in the hepatic cells. In particular, increased hepatocyte steatosis and cell death were associated with fat-induced histone lactylation. Similarly, increased histone lactylation has been linked to hepatic macrophages and hepatic stellate cell activation in MASH. These findings highlight the complex interplay between metabolic reprogramming and epigenetic remodeling in MASH progression and suggest potential therapeutic targets to counter lipogenic, inflammatory, and fibrotic events in MASH.