HFCD exposure compromises the intestinal barrier and triggers NASH development in mice.[25, 26] We observed upregulation of NSD2 and H3k36me2 expression in the colons of mice fed HFCD for 18 weeks (Figure 1G,H), consistent with clinical samples, while the expression levels of Nsd1, Nsd3, and other histone proteins potentially modified by NSD2 remained largely unchanged (Figure S1F,G, Supporting Information). This evidence concerns the gene NSD3 and metabolic dysfunction-associated steatohepatitis.