Fig. 3: Intestinal Tm6sf2 deficiency promotes MASH by inducing metabolite alteration.
a,b, PCA and PLS-DA of untargeted metabolomic profiling (a), and heat map of differential metabolites (b) in stools (n = 5 per group), portal vein serum (n = 4 per group) and liver tissues (n = 5 per group) of NC-fed Tm6sf2ΔIEC and Tm6sf2fl mice. c, LPA-targeted metabolomics on portal vein serum of Tm6sf2ΔIEC and Tm6sf2fl mice fed with NC (n = 4 per group), CD-HFD (n = 9 per group) or HFHC diet (n = 7 per group). d, LPA-targeted metabolomics on liver tissues of mice fed with NC (n = 4 per group) or HFHC diet (n = 7 per group). e, Correlation analysis between differential bacteria and LPA levels in stools, portal vein serum and liver tissues of Tm6sf2ΔIEC and Tm6sf2fl mice. *P < 0.05, **P < 0.01. f, LPS-targeted metabolomics in stools, portal vein serum and liver tissues of germ-free mice gavaged with Lachnospiraceae for 10 days (n = 5 per group). g,h, Representative images of Oil Red O staining with stained area normalized to cell number (n = 5 per group), cellular triglyceride and lipid peroxidation normalized to total protein content (n = 3 per group), and supernatant TNF level (n = 3 per group) of AML-12 mouse normal hepatocytes (g) or THLE-2 human normal hepatocytes (h) under LPA treatment with or without LPAR inhibitor AM095. Results are presented as the mean ± s.d. Statistical significance was determined by Adonis test (a), two-tailed Student’s t-test (c, d and f, left and right), two-tailed Mann–Whitney U test (f, middle), Spearman’s correlation analysis (e) or one-way analysis of variance (ANOVA) followed by Turkey’s multiple comparison (g and h).
