Astrocyte Elevated Gene-1/Metadherin (AEG-1/MTDH) in Myeloid Cells Regulates Metabolic Dysfunction-Associated Steatohepatitis (MASH) [Spatial Transcriptomics]

Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) 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. Both male and female AEG-1?MAC mice were significantly protected from MASH development compared to AEG-1fl/fl mice. Overall design: Littermates of myeloid cell-specific AEG-1 knockout mice (AEG-1DMAC) and AEG-1 floxed mice (AEG-1fl/fl) were fed either control diet (CD) or HF/HSD for 20 weeks.

星形胶质细胞上调基因1/黏附素（Astrocyte elevated gene-1/Metadherin, AEG-1/MTDH）可调控肝细胞脂质代谢与炎症过程，并在代谢功能障碍相关脂肪性肝炎（metabolic dysfunction-associated steatohepatitis, MASH）的发生发展中发挥促进作用。髓系细胞（如巨噬细胞）在炎症调控中具有关键功能。本研究探究了AEG-1在髓系细胞中对高脂高糖饮食（high fat/high sugar diet, HF/HSD）诱导的MASH的调控作用。相较于AEG-1 floxed小鼠（AEG-1fl/fl），雄性与雌性髓系细胞特异性AEG-1敲除小鼠（AEG-1ΔMAC）均能显著抵御MASH的发生发展。整体实验设计：将髓系细胞特异性AEG-1敲除小鼠（AEG-1ΔMAC）与AEG-1 floxed小鼠（AEG-1fl/fl）的同窝仔鼠分别饲喂正常对照饮食（control diet, CD）或高脂高糖饮食，干预时长为20周。