Intestinal NSD2 aggravates hepatic steatosis during obesity through histone modifications [RNA-seq]
The impairment of the intestinal barrier will lead to the accumulation of fat and harmful substances in the liver, inducing hepatic steatosis or steatohepatitis. Zhang et al. identified NSD2 in the intestine as a novel and essential regulator of hepatic steatosis. NSD2 directly regulates transcriptional activation of ERN1 through the modification of H3 dimethylated on lysine 36 (H3K4me36), thereby activating the ERN1-JNK axis to induce inflammatory response, intestinal barrier impairment, and hepatic steatosis. This functional mechanism of NSD2 provides a potential therapeutic target for this disease. Overall design: Intestinal-specific NSD2 disruption mice (NSD2?IE) and controls (NSD2fl/fl) were treated with a 16-week HFCD diet, and colon tissues were collected for further study, with three replicate samples per group