Researchers utilized advanced single-cell and spatial multi-omics to map the cellular landscape of metabolic dysfunction-associated steatotic liver disease (MASLD) as it progresses toward more severe stages. A primary finding is the significant expansion of lipid-associated macrophages (LAMs), which are characterized by a specific phenotype driven by the MITF transcription factor. This regulatory pathway enhances fatty acid oxidation and mitochondrial function through the PGC1α–PPARγ axis, helping the liver manage lipid overload. Furthermore, the study suggests that these specialized macrophages exert a hepatoprotective effect by secreting growth factors that promote cell survival and limit tissue damage. By integrating transcriptomic and metabolic data, the authors identified potential therapeutic targets, such as the RSPO3–LGR6 signaling pair, to address inflammation and fibrosis. Overall, these findings provide a comprehensive spatiotemporal reference for understanding the immune and metabolic shifts that occur during chronic liver injury.

References:

• Li Z, Luo G, Gan C, et al. Spatially resolved multi-omics of human metabolic dysfunction-associated steatotic liver disease[J]. Nature Genetics, 2025: 1-14.