Myeloid AEG-1/MTDH drives inflammation and hepatocellular dysfunction in diet-induced steatohepatitis

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Astrocyte elevated gene-1 (AEG-1)/metadherin plays an important role in regulating lipid metabolism and inflammation in hepatocytes and promotes metabolic dysfunction-associated steatohepatitis (MASH). Myeloid cells, such as macrophages, play a key role in regulating inflammation. Here, we investigated the role of AEG-1 in myeloid cells in regulating high fat)/high sugar diet (HF/HSD)-induced MASH. Littermates of myeloid cell-specific AEG-1 knockout mice (AEG-1 ΔMAC ) and AEG-1 floxed mice (AEG-1 fl/fl ) were fed either a control diet or an HF/HSD for 20 weeks. Both male and female AEG-1 ΔMAC mice were significantly protected from MASH development compared with AEG-1 fl/fl mice. In control diet-fed mice, spatial transcriptomics analysis revealed inhibition of hepatic steatosis and development of hepatocellular carcinoma and activation of fatty acid β-oxidation in the periportal and pericentral hepatocytes of AEG-1 ΔMAC livers. Single-cell RNA-Seq, performed in HF/HSD-fed mice, identified a significant decrease in the total number of Kupffer cells in AEG-1 ΔMAC versus AEG-1 fl/fl livers. A marked inhibition of inflammation and fibrosis in Kupffer cells and stellate cells, increased fatty acid β-oxidation in stellate and endothelial cells, and inhibition of proliferation and invasion in the hepatocytes, especially in pericentral hepatocytes, were observed in AEG-1 ΔMAC liver vers

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.