[Research advances on hepatocyte zonal changes in metabolic associated fatty liver disease]

Hepatocyte zonation is a core feature of the spatial heterogeneity of liver function, which is driven by the process of gradients of oxygen and nutrients from the portal vein to the central vein and is precisely regulated by signaling pathways such as Wnt/β-catenin, thereby forming distinct metabolic functional zones. This zonation mechanism is crucial to preserving hepatic metabolic homeostasis. However, zonation stability is disrupted in metabolic associated fatty liver disease (MAFLD). The pericentral venous zone (Zone 3) is the initial site of steatosis and oxidative stress due to lipid metabolism imbalance and hypoxic sensitivity, while the periportal venous zone (Zone 1) exhibits metabolic abnormalities associated with insulin resistance. Furthermore, the dissemination of inflammatory activation and fibrosis from Zone 3 to the entire lobule with zonation disruption facilitates disease progression. Therefore, an in-depth understanding of the hepatocyte zonation mechanism is of enormous significance for revealing the pathogenesis, pathological evolution, and treatment strategies of MAFLD. This article systematically explains that the homeostasis of hepatocyte zonation is fundamental to maintaining a healthy liver, whereas zonation disorders are a central factor driving MAFLD progression, providing a theoretical basis for understanding pathogenesis from a spatial metabolism perspective and exploring new therapeutic strategies based on recent research findings.