Extended Data Fig. 8: Fructose-induced upregulation of YAP target genes and attenuation of TJP mRNA downregulation, barrier deterioration, hepatosteatosis and induction of DNL-related proteins in MUP-uPA/gp130Act and CCN1-treated mice.
From: Fructose stimulated de novo lipogenesis is promoted by inflammation
a, b, Expression of indicated mRNAs in BL6 enteroids maintained in media containing the indicated glucose and fructose concentrations (mM) (n = 3, enteroids isolated from three separate male mice; the experiment was repeated twice with similar results). a, and in colonic mucosa of MUP-uPA mice (n=8 per group) (b) was measured by Q-RT- PCR. c, Enteroids from MUP-uPA and MUP- uPA/gp130Act mice (n = 4, enteroids isolated from four different mice per group) were incubated with 20 mM fructose. Expression of indicated mRNAs was measured by Q-RT-PCR. This experiment was repeated twice with similar results. d, e, Expression of antimicrobial (d) and TJP (e) mRNAs in colon tissues of MUP- uPA/gp130Act (MUP-uPA/Tg) mice fed CSD (n = 9 per group) or HFrD (n = 8 per group) compared to MUP-uPA mice fed HFrD for five months (n = 9 per group). Asterisks indicate significant changes between MUP-uPA and MUP-uPA/Tg mice fed HFrD. f, IB analysis of claudin-1 in colons of MUP-uPA/gp130Act and MUP-uPA mice kept on CSD or HFrD as indicated. A representative blot is shown. g, FITC-dextran serum concentrations in indicated mice (n = 6 serum samples per group). h, Serum endotoxin concentrations in indicated mice measured by ELISA (n = 8 serum samples per group). i, F1P abundance in liver and jejunum of indicated mice (arbitrary units; n = 7 samples per group). j–p, 6-week-old MUP-uPA male mice were fed HFrD for 3 months and i.p. injected 2 μg CCN1 or vehicle (PBS) every other day for the last 4 weeks of HFrD feeding. Length (j) and TJP mRNA expression (k) were determined on excised colons (n = 7 per group). Fecal albumin was measured by ELISA (n = 8 serum samples per group) (l). ORO staining (n = 6 tissue samples) and triglyceride concentrations (n = 8 samples per group) (m), inflammatory and lipogenic gene expression (n = 7 per group) (n) and FAS protein amounts (n = 7 per group), representative blots (o) were determined in liver tissue. p, Body weight was measured at the end of the CCN1 treatment course on 7 male mice per group (n = 7). q, Endotoxin levels in serum of indicated mice (n = 3 per group). Scale bars, 100 μm. In panels a, d, e, g, h and q one-way ANOVA with Tukey’s multiple comparison test was used to determine mean ± SEM. Two-sided Student’s t test was used to determine mean ± SEM in panels b, c, i-n, and p. *P < 0.05, **P < 0.01, ***P < 0.001. Benjamini-Hochberg FDR adjustment for P-values has been performed on data presented in panels c, k and n.
