Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas.
Kuhre, Rune E
Jepsen, Sara L
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Kuhre, R. E., Wewer Albrechtsen, N. J., Larsen, O., Jepsen, S. L., Balk-Møller, E., Andersen, D. B., Deacon, C. F., et al. (2018). Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas.. Molecular metabolism, 11 84-95. https://doi.org/10.1016/j.molmet.2018.03.007
Objective: Bile acids (BAs) facilitate fat absorption and may play a role in glucose and metabolism regulation, stimulating the secretion of gut hormones. The relative importance and mechanisms involved in BA-stimulated secretion of appetite and metabolism regulating hormones from the gut and pancreas is not well described and was the purpose of this study. Methods: The effects of bile acids on the secretion of gut and pancreatic hormones was studied in rats and compared to the most well described nutritional secretagogue: glucose. The molecular mechanisms that underlie the secretion was studied by isolated perfused rat and mouse small intestine and pancreas preparations and supported by immunohistochemistry, expression analysis and pharmacological studies. Results: Bile acids robustly stimulate secretion of not only the incretin hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1), but also glucagon and insulin in vivo, to levels comparable to those resulting from glucose stimulation. The mechanisms of GLP-1, neurotensin and peptide YY (PYY) secretion was secondary to intestinal absorption and depended on activation of basolateral membrane TGR5 receptors on the L-cells in the following order of potency: Litocholic acid >DeoxyCholicAcid>ChenoDCA>CA. Thus BAs did not stimulate secretion of GLP-1 and PYY from perfused small intestine in TGR5 K.O. mice but stimulated robust resposes in wild type littermates. TGR5 is not expressed on alpha cells or beta cells, and BAs had no direct effects on glucagon or insulin secretion from the perfused pancreas. Conclusion: BAs should be considered not only as fat emulsifiers but also as important regulators of appetite- and metabolism-regulating hormones by activation of basolateral intestinal TGR5.
Intestinal Mucosa, Pancreas, Cells, Cultured, COS Cells, Animals, Mice, Inbred C57BL, Mice, Rats, Rats, Wistar, Bile Acids and Salts, Gastric Inhibitory Polypeptide, Peptide YY, Receptors, G-Protein-Coupled, Male, Glucagon-Like Peptide 1, Chlorocebus aethiops
WELLCOME TRUST (106262/Z/14/Z & 106263/Z/14/Z)
EC FP7 CP (266408)
Embargo Lift Date
External DOI: https://doi.org/10.1016/j.molmet.2018.03.007
This record's URL: https://www.repository.cam.ac.uk/handle/1810/276623
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: http://creativecommons.org/licenses/by-nc-nd/4.0/
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