Bile Formation and the Enterohepatic Circulation

Dawson, Paul A.

doi:10.1016/b978-0-12-382026-6.00053-1

Cited by 14 publications

(1 citation statement)

References 246 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The past 20 years have witnessed a great expansion in our understanding of the role bile acids play in both normal physiology and disease as well as the complex processes that maintain bile acid homeostasis. 1 Despite these advances, there remains a paucity of tools to examine bile acid transport in vivo. To address this limitation, we investigated the potential of using bile acid analogues labeled with naturally occurring fluorine, 19 F, and in vivo magnetic resonance imaging (MRI) to visualize bile acids in anatomical compartments, primarily the gallbladder.…”

Section: Introductionmentioning

confidence: 99%

Attenuated Accumulation of Novel Fluorine (¹⁹F)-Labeled Bile Acid Analogues in Gallbladders of Fibroblast Growth Factor-15 (FGF15)-Deficient Mice

et al. 2018

View full text Add to dashboard Cite

Our work has focused on defining the utility of fluorine (19F)-labeled bile acid analogues and magnetic resonance imaging (MRI) to identify altered bile acid transport in vivo. In the current study, we explored the ability of this approach to differentiate fibroblast growth factor-15 (FGF15)- deficient from wild-type (WT) mice, a potential diagnostic test for bile acid diarrhea, a commonly misdiagnosed disorder. FGF15 is the murine homologue of human FGF19, an intestinal hormone whose deficiency is an underappreciated cause of bile acid diarrhea. In a pilot and three subsequent pharmacokinetic studies, we treated mice with two 19F-labeled bile acid analogues, CA-lys-TFA and CA-sar-TFMA. After oral dosing, we quantified 9F-labeled bile acid analogue levels in the gallbladder, liver, small and large intestine, and plasma using liquid chromatography mass spectrometry (LC-MS/MS). Both 19F bile acid analogues concentrated in the gallbladders of FGF15-deficient and WT mice, attaining peak concentrations at approximately 8.5 h after oral dosing. However, analogue levels in gallbladders of FGF15-deficient mice were several-fold less compared to those in WT mice. Live-animal 19F MRI provided agreement with our LC-MS/MS-based measures; we detected robust CA-lys-TFA 19F signals in gallbladders of WT mice but no signals in FGF15-deficient mice. Our finding that 19F MRI differentiates FGF15-deficient from WT mice provides additional proof-of-concept for the development of 19F bile acid analogues and 19F MRI as a clinical test to diagnose bile acid diarrhea due to FGF19 deficiency and other disorders.

show abstract

Section: Introductionmentioning

confidence: 99%

Attenuated Accumulation of Novel Fluorine (¹⁹F)-Labeled Bile Acid Analogues in Gallbladders of Fibroblast Growth Factor-15 (FGF15)-Deficient Mice

et al. 2018

View full text Add to dashboard Cite

show abstract

Small Intestinal Function

Blikslager

2017

The Equine Acute Abdomen

View full text Add to dashboard Cite

Lithocholic Acid Stimulates IL-8 Expression in Human Colorectal Cancer Cells Via Activation of Erk1/2 MAPK and Suppression of STAT3 Activity

et al. 2017

View full text Add to dashboard Cite

The secondary bile acid lithocholic acid (LCA), an established tumor promoter, has been implicated in colorectal cancer (CRC) metastasis. Overexpression of interleukin-8 (IL-8) has been detected in CRC, and it contributes to poor prognosis. However, the effect of LCA on IL-8 expression is still undefined. In this study, we observed that LCA treatment induced IL-8 expression in CRC HCT116 cells. Pharmacological inhibition and mutagenesis studies indicated that Erk1/2 is critical for LCA-induced IL-8 expression. Furthermore, LCA reduced the phosphorylation of STAT3, and the STAT3 inhibitor Stattic, accelerated LCA-induced IL-8 expression, suggesting that STAT3 is involved in LCA-induced IL-8 expression. Activation of Erk1/2 functioned as an upstream signal of the STAT3 suppression induced by LCA. In conclusion, LCA activated Erk1/2 and in turn, suppressed STAT3 phosphorylation to induce IL-8 expression in HCT116 cells, thus stimulating endothelial cell proliferation and tube like formation. J. Cell. Biochem. 118: 2958-2967, 2017. © 2017 Wiley Periodicals, Inc.

show abstract

Bile Formation and the Enterohepatic Circulation

Cited by 14 publications

References 246 publications

Attenuated Accumulation of Novel Fluorine (¹⁹F)-Labeled Bile Acid Analogues in Gallbladders of Fibroblast Growth Factor-15 (FGF15)-Deficient Mice

Attenuated Accumulation of Novel Fluorine (¹⁹F)-Labeled Bile Acid Analogues in Gallbladders of Fibroblast Growth Factor-15 (FGF15)-Deficient Mice

Small Intestinal Function

Lithocholic Acid Stimulates IL-8 Expression in Human Colorectal Cancer Cells Via Activation of Erk1/2 MAPK and Suppression of STAT3 Activity

Contact Info

Product

Resources

About

Bile Formation and the Enterohepatic Circulation

Cited by 14 publications

References 246 publications

Attenuated Accumulation of Novel Fluorine (19F)-Labeled Bile Acid Analogues in Gallbladders of Fibroblast Growth Factor-15 (FGF15)-Deficient Mice

Attenuated Accumulation of Novel Fluorine (19F)-Labeled Bile Acid Analogues in Gallbladders of Fibroblast Growth Factor-15 (FGF15)-Deficient Mice

Small Intestinal Function

Lithocholic Acid Stimulates IL-8 Expression in Human Colorectal Cancer Cells Via Activation of Erk1/2 MAPK and Suppression of STAT3 Activity

Contact Info

Product

Resources

About

Attenuated Accumulation of Novel Fluorine (¹⁹F)-Labeled Bile Acid Analogues in Gallbladders of Fibroblast Growth Factor-15 (FGF15)-Deficient Mice

Attenuated Accumulation of Novel Fluorine (¹⁹F)-Labeled Bile Acid Analogues in Gallbladders of Fibroblast Growth Factor-15 (FGF15)-Deficient Mice