Fig. 1: Intestinal Tm6sf2 deficiency in mice triggers MASH.
a, Experimental schematic of Tm6sf2ΔIEC and Tm6sf2fl male mice fed with NC for 4 or 12 months. b,c, Representative small intestine images of TM6SF2 immunohistochemistry (b), and TM6SF2 protein expression in small intestine and liver tissues (c) of Tm6sf2ΔIEC and Tm6sf2fl mice (n = 5 per group). d, Representative liver images of Oil Red O and H&E staining and hepatic triglyceride of Tm6sf2ΔIEC and Tm6sf2fl mice fed with NC for 4 months (n = 5 per group). e–h, Representative liver images of Oil Red O and H&E staining with histological scoring and hepatic triglyceride (n = 5 per group; e) and hepatic protein expression of NF-κB pathway markers (Tm6sf2ΔIEC, n = 3; Tm6sf2fl, n = 5; f), flow cytometric analysis of hepatic macrophage (MΦ) populations (Tm6sf2ΔIEC, n = 4; Tm6sf2fl, n = 5; g) and volcano plot and Gene Ontology enrichment analysis of RNA sequencing on liver tissues (n = 5 per group; h) of Tm6sf2ΔIEC and Tm6sf2fl mice at 12 months of age. i, Experimental schematic, representative hepatic images of Oil Red O and H&E staining with histological scoring and hepatic triglyceride and serum ALT levels of Tm6sf2ΔIEC and Tm6sf2fl female mice fed with NC for 12 months (n = 9 per group). j,k, Experimental schematic and representative liver images of Oil Red O and H&E staining with histological scoring (n = 9 per group; j) and hepatic protein expression of NF-κB pathway markers (n = 3 per group; k) of Tm6sf2ΔIEC and Tm6sf2fl male mice fed with CD-HFD for 2 months. l, Representative liver images of Sirius Red staining and hepatic hydroxyproline of Tm6sf2ΔIEC and Tm6sf2fl mice fed with CD-HFD for 14 months (n = 7 per group). Results are presented as the mean ± s.d. Statistical significance was determined by two-tailed Student’s t-test (d, g, i and j), two-tailed Mann–Whitney U test (e and l), DESeq2 (h, left) or clusterProfiler (h, right). Tm6, Tm6sf2.
