Figure 9.

Antibiotic treatment prevents the exacerbation of high-fat diet–induced metabolic syndrome, steatosis, and fibrosis that resulted from loss of hepatocyte TLR5. TLR5^fl/fl and TLR5^ΔHep mice were fed with a regular chow diet or a HFD, comprising 60% fat, for 8 weeks, with or without broad-spectrum antibiotics (ampicillin/neomycin), administered via drinking water. (A) Analysis of 16S mRNA expression by quantitative RT-PCR in the liver of TLR5^fl/fl and TLR5^ΔHep mice. (B) Body weight, (C) fat-pad weights, (D) 15-hour fasting blood glucose concentration, and (E) liver weights were measured. (F and G) Liver lipid staining using Oil Red O with (F) representative images and (G) quantification shown. (H) Serum ALT concentrations. (I–L) Liver mRNAs were isolated and quantitated for expression of genes involved in inflammation and fibrosis: (I) tumor necrosis factor (TNF)-α, (J) TIMP1, (K) collagen 1, and (L) matrix metalloprotease 9. (M and N) Liver mRNAs were isolated and quantitated for expression of genes involved in inflammation: (M) MCP1 and (N) interferon (IFN)-γ. (O and P) Adipose tissue mRNAs were isolated and quantitated for expression of genes involved in inflammation: (O) CXCL1 and (P) IL6. Results are expressed as relative values compared with TLR5^fl/fl mice fed a high-fat diet, defined as 1. (Q and R) Liver fibrosis estimation using Sirius red staining with (Q) representative images and (R) quantification shown. (S) Liver fibrosis estimation using Masson's trichrome staining with representative images shown. Scale bar: 50 μm. Data are the means ± SEM. N = 3–5. Significance was determined by the Student t test. *P < .05.