Abstract
The cycle of gallbladder filling and emptying controls the flow of bile into the intestine for digestion. Here we show that fibroblast growth factor-15, a hormone made by the distal small intestine in response to bile acids, is required for gallbladder filling. These studies demonstrate that gallbladder filling is actively regulated by an endocrine pathway and suggest a postprandial timing mechanism that controls gallbladder motility.
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Acknowledgements
We thank T. Reh (University of Washington) for the Fgf15−/− mice; J. Shelton, the Pathology Core Group, and members of S.A.K. and D.J.M.'s laboratories for technical assistance; and S. Cary for graphics. This work was funded by US National Institutes of Health grants DK067158 (S.A.K.) and U19DK62434 (S.A.K., D.J.M. and H.E.X.), the Robert A. Welch Foundation (S.A.K. and D.J.M.), the Jay and Betty Van Andel Foundation (H.E.X.) and the Howard Hughes Medical Institute (D.J.M.). D.J.M. is an investigator of the Howard Hughes Medical Institute.
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M.C. contributed to all the experiments. A.M. conducted bile flow measurements and provided gallbladder expertise. A.L.B. conducted gallbladder volume measurements. L.P. contributed all the mice and assisted with the CCK measurements. M.U. conducted tensiometry experiments. S.R.H. conducted bile flow measurements. K.S.-P. and H.E.X. prepared the FGF19 protein. J.A.R. conducted and analyzed the histology. R.D.G. prepared the FGF15 protein. D.J.M. and S.A.K. supervised the project and wrote the paper.
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Supplementary information
Supplementary Fig. 1
Fgf15 mRNA concentrations were measured by real-time quantitative PCR in total RNA prepared from ileum, liver, gallbladder (GB), common bile duct (BD) and sphincter of Oddi (SO) of wild type mice (n = 3/group). (PDF 12 kb)
Supplementary Fig. 2
(a) Bile flow rate was measured in fasted Fgf15−/− mice (n = 4/group) either before (basal) or after administration of forskolin (200 μg/kg) by tail vein injection. (PDF 19 kb)
Supplementary Fig. 3
Representative tracings of tension recordings from gallbladders pre-contracted with 1 nM CCK and subsequently treated with vehicle (a), 700 nm FGF19 (b), or 2 μM forskolin (c) as indicated. (PDF 62 kb)
Supplementary Table 1
Sex, age, and body weight data for the mice used to generate the data presented in the figures. (PDF 80 kb)
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Choi, M., Moschetta, A., Bookout, A. et al. Identification of a hormonal basis for gallbladder filling. Nat Med 12, 1253–1255 (2006). https://doi.org/10.1038/nm1501
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DOI: https://doi.org/10.1038/nm1501
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