Figure 4

Feeding antimicrobials to pigs enhance the circulating concentration of FGF19 by targeting intestinal FXR. Two independent cohorts of piglets were weaned and fed for 35 days cereal-based diets medicated with combinations of AMA, which were either zinc oxide, amoxicillin, and colistin (ZAC) or zinc oxide, chlortetracycline, and tiamulin (ZCT) at dosing levels routinely used for preventing bacterial enteritis and stimulating pig growth. Control pigs (CON) received no AMA. Gene expression was measured by qRT-PCR and protein levels by Western blot and ELISA in tissue samples taken on days 34 and 35 or ileal explants. Data from the two experiments were combined in the figure. (A,B) Ileal expression of genes encoding components of the FGF19 system and (C,D) concentration of FGF19 protein in ileum (C) and plasma (D) of pigs fed CON or ZAC. (E–G) Expression of genes encoding components of the FGF19 system in ileum (E), sWAT (F), and skeletal muscle (G,H) plasma concentration of FGF19 protein in pigs fed CON or ZCT. In C, FGF19 and β-actin specific bands are displayed from cropped blots. Full-length blots are presented in Supplementary Figure S7. Data were analyzed with ANOVA. Least squares means ± SEM are plotted, ^***P < 0.001, n = 9–12 per group. (I,J) Expression of Fgf19 in ileal explants treated with 300 μM of CDCA or HCA (I) or with 3000 μM of CDCA in the presence of different amounts of HCA (J). Data were analyzed with Student t test. Means ± SE are plotted, ^*P < 0.05. This assay was performed using explants from 4 independent pigs from the CON group.