Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas.
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Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas. / Kuhre, Rune Ehrenreich; Albrechtsen, Nicolai Jacob Wewer; Larsen, Olav; Jepsen, Sara Lind; Balk-Møller, Emilie; Andersen, Daniel Bjørklund; Deacon, Carolyn F.; Schoonjans, Kristina; Reimann, Frank ; Gribble, Fiona M.; Albrechtsen, Reidar; Hartmann, Bolette; Rosenkilde, Mette; Holst, Jens Juul.
In: Molecular Metabolism, Vol. 11, 2018, p. 84-95.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas.
AU - Kuhre, Rune Ehrenreich
AU - Albrechtsen, Nicolai Jacob Wewer
AU - Larsen, Olav
AU - Jepsen, Sara Lind
AU - Balk-Møller, Emilie
AU - Andersen, Daniel Bjørklund
AU - Deacon, Carolyn F.
AU - Schoonjans, Kristina
AU - Reimann, Frank
AU - Gribble, Fiona M.
AU - Albrechtsen, Reidar
AU - Hartmann, Bolette
AU - Rosenkilde, Mette
AU - Holst, Jens Juul
PY - 2018
Y1 - 2018
N2 - 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 Takeda G-protein receptor 5 (TGR5) receptors on the L-cells in the following order of potency: Lithocholic acid (LCA) >Deoxycholicacid (DCA)>Chenodeoxycholicacid (CDCA)> Cholic acid (CA). Thus BAs did not stimulate secretion of GLP-1 and PYY from perfused small intestine in TGR5 KO mice but stimulated robust responses in wild type littermates. TGR5 is not expressed on α-cells or β-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.
AB - 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 Takeda G-protein receptor 5 (TGR5) receptors on the L-cells in the following order of potency: Lithocholic acid (LCA) >Deoxycholicacid (DCA)>Chenodeoxycholicacid (CDCA)> Cholic acid (CA). Thus BAs did not stimulate secretion of GLP-1 and PYY from perfused small intestine in TGR5 KO mice but stimulated robust responses in wild type littermates. TGR5 is not expressed on α-cells or β-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.
KW - Bile-acids
KW - GLP-1
KW - Insulin
KW - Neurotensin
KW - PYY
KW - TGR5
U2 - 10.1016/j.molmet.2018.03.007
DO - 10.1016/j.molmet.2018.03.007
M3 - Journal article
C2 - 29656109
VL - 11
SP - 84
EP - 95
JO - Molecular Metabolism
JF - Molecular Metabolism
SN - 2212-8778
ER -
ID: 195192727