Extended Data Fig. 5: Fructose-induced endotoxemia, hepatosteatosis, HCC, liver fibrosis, glucose intolerance and colonic inflammation are inhibited by antibiotics.
From: Fructose stimulated de novo lipogenesis is promoted by inflammation
a, CSD and HFrD-fed MUP-uPA (n=8 CSD, n=9 HfrD, n=7 HFrD+Abx) and DEN- challenged BL6 (n = 9 per group) male mice were treated or not with a broad-spectrum Abx cocktail for 5 months, after which serum endotoxin concentrations were measured. b, HCC burden in MUP-uPA (n=9 HFrD, n=7 HFrD+Abx) and DEN- challenged BL6 (n=11 HFrD, n=9 HFrD+Abx) male mice given HFrD alone or HFrD plus Abx cocktail. c, Hepatosteatosis in MUP-uPA and DEN-challenged BL6 male mice given HFrD ± Abx for 5 months determined by ORO staining of liver sections (n = 6). Scale bars, 100 μm. d, Liver triglyceride content in above mice (n = 6 per group). e–g, Expression of lipogenic (e) and inflammatory (f) genes (n = 9 HFrD, n = 7 HFrD+Abx) and IB analysis of liver ACC1 and FAS (g). h, i, Liver F1P abundance (MUP-uPA; n = 7 samples from different mice per group) (h) and cytosolic acetyl-CoA (n = 8 HFrD, n = 7 HFrD+Abx samples from different mice per group; the HFrD bar is same as in Extended Data Fig. 2a). j, k, glucose tolerance (MUP-uPA, n = 10 serum samples from different mice per group, BL6, n = 7 serum samples from different mice per group) (j) and non- fasting serum insulin (n = 8 HFrD, n = 7 HFrD+Abx serum samples from different mice per group) (k). l, Total body and white adipose tissue weights in indicated male mice (MUP- UPA, n = 9 HFrD, n = 7 HFrD+Abx; BL6, n = 12 HFrD, n = 10 HFrD+Abx) (m) Liver fibrosis in HFrD-fed MUP-uPA mice was examined by Sirius Red staining (n = 7), representative images. n, Colon length in indicated mouse strains (MUP-uPA, n = 9 HFrD, n = 7 HFrD+Abx; BL6 n = 12 HFrD, n = 10 HFrD+Abx ; the HFrD bars are same as in Extended Data Fig. 1f). Scale bars, 100 μm. Unpaired two-sided Student’s t test was used in panels b, d-f, h, I, k, l and n to determine mean ± SEM, whereas panel a was analyzed by one way ANOVA and Tukey’s multiple comparison test and panel j was analyzed using two way ANOVA and Sidak’s multiple comparison test. *P < 0.05, **P < 0.01, ***P < 0.001. Benjamini-Hochberg FDR adjustment for P-values has been performed on data presented in panels e and f.
