Diminished gallbladder filling, increased fecal bile acids, and promotion of colon epithelial cell proliferation and neoplasia in fibroblast growth factor 15-deficient mice

• Published in: Oncotarget 2018-05, Vol.9 (39), p.25572-25585
• Main Authors: Cheng, Kunrong, Metry, Melissa, Felton, Jessica, Shang, Aaron C, Drachenberg, Cinthia B, Xu, Su, Zhan, Min, Schumacher, Justin, Guo, Grace L, Polli, James E, Raufman, Jean-Pierre
• Format: Article
• Language: English
• Subjects: Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.25385

Fibroblast growth factor-19 (human FGF19; murine FGF15) suppresses bile acid synthesis. In FGF19 deficiency, diarrhea resulting from bile acid spillage into the colon mimics irritable bowel syndrome. To seek other consequences of FGF19/15 deficiency, we used and wild-type (WT) mice to assess gallbladder filling, the bile acid pool, fecal bile acid levels, and colon neoplasia. We fasted mice for six hours before assessing gallbladder size by magnetic resonance imaging (MRI). We measured bile acid levels in different compartments by enzymatic assay, and induced colon neoplasia with azoxymethane (AOM)/dextran sodium sulfate (DSS) and quantified epithelial Ki67 immunostaining and colon tumors 20 weeks later. MRI confirmed the gross finding of tubular gallbladders in FGF15-deficient compared to WT mice, but fasting gallbladder volumes overlapped. After gavage with a bile acid analogue, MRI revealed diminished gallbladder filling in FGF15-deficient mice ( = 0.0399). In FGF15-deficient mice, the total bile acid pool was expanded 45% (