Extended Data Fig. 3: HFrD feeding downregulates TJP mRNAs and induces ER stress, colonic inflammation and barrier deterioration.
From: Fructose stimulated de novo lipogenesis is promoted by inflammation
a, b, Expression of TJP genes in colon (a) and jejunum (b) of MUP- uPA male mice fed HFrD with (a, n = 6 or 7; b, n = 6) or without (a, n = 9; b, n = 7) concomitant Abx treatment. c, IB analysis of indicated TJP in colon tissue of above mice (n = 9 no Abx, n=7 plus Abx). Representative blots are shown. d, Expression of Il22 mRNA and IL-22 regulated genes in colon tissue of CSD-, HFrD-, or HFrD + Abx-fed MUP- uPA male mice (n = 9 no Abx, n = 7 plus Abx). e, f, Male BL6 mice (e, n = 8 per group; f = 10 per group) were given 30% fructose in drinking water and fed NCD for 5 (e) or 3 (f) months and mRNA amounts of TJP genes in colon and jejunum (e), colon length and FITC-dextran serum levels were measured (f). g, h, Male BL6 mice were given regular water with or without 30% sucrose and fed NCD for 3 months. Colon length and FITC-dextran serum levels (n = 10 per group) (g), colon TJP mRNAs (h) and ER stress marker mRNAs (i) (h and i, n = 9 per regular water group and n = 8 per 30% sucrose group) were measured. j, Chop and sXbp1 mRNA amounts in fructose and glucose treated organoids (isolated from 3 different male mice). j-m, Expression of indicated mRNAs in BL6 enteroids (isolated from 3 different male mice) maintained in media containing the indicated glucose and/or fructose concentrations (mM) and treated with KHK inhibitor (k and l), TUDCA (m) or vehicle. Unpaired two-sided Student’s t test was used in all panels, other than c, to determine Mean ± SEM, *P < 0.05, **P < 0.01, ***P < 0.001. Benjamini- Hochberg FDR adjustment for P-values has been performed on data presented in panels a, b, d, e and h-m. Experiments on enteroids have been repeated twice with similar results.
