Publication

Potential of Intestine-Selective FXR Modulation for Treatment of Metabolic Disease

van Zutphen, T., Bertolini, A., de Vries, H. D., Bloks, V. W., de Boer, J. F., Jonker, J. W. & Kuipers, F., 25-Jun-2019, Bile Acids and Their Receptors. Springer, p. 207-234 28 p. (Handbook of Experimental Pharmacology).

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

APA

van Zutphen, T., Bertolini, A., de Vries, H. D., Bloks, V. W., de Boer, J. F., Jonker, J. W., & Kuipers, F. (2019). Potential of Intestine-Selective FXR Modulation for Treatment of Metabolic Disease. In Bile Acids and Their Receptors (pp. 207-234). (Handbook of Experimental Pharmacology). Springer. https://doi.org/10.1007/164_2019_233

Author

van Zutphen, Tim ; Bertolini, Anna ; de Vries, Hilde D ; Bloks, Vincent W ; de Boer, Jan Freark ; Jonker, Johan W ; Kuipers, Folkert. / Potential of Intestine-Selective FXR Modulation for Treatment of Metabolic Disease. Bile Acids and Their Receptors. Springer, 2019. pp. 207-234 (Handbook of Experimental Pharmacology).

Harvard

van Zutphen, T, Bertolini, A, de Vries, HD, Bloks, VW, de Boer, JF, Jonker, JW & Kuipers, F 2019, Potential of Intestine-Selective FXR Modulation for Treatment of Metabolic Disease. in Bile Acids and Their Receptors. Handbook of Experimental Pharmacology, Springer, pp. 207-234. https://doi.org/10.1007/164_2019_233

Standard

Potential of Intestine-Selective FXR Modulation for Treatment of Metabolic Disease. / van Zutphen, Tim; Bertolini, Anna; de Vries, Hilde D; Bloks, Vincent W; de Boer, Jan Freark; Jonker, Johan W; Kuipers, Folkert.

Bile Acids and Their Receptors. Springer, 2019. p. 207-234 (Handbook of Experimental Pharmacology).

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

Vancouver

van Zutphen T, Bertolini A, de Vries HD, Bloks VW, de Boer JF, Jonker JW et al. Potential of Intestine-Selective FXR Modulation for Treatment of Metabolic Disease. In Bile Acids and Their Receptors. Springer. 2019. p. 207-234. (Handbook of Experimental Pharmacology). https://doi.org/10.1007/164_2019_233


BibTeX

@inbook{9b325bd4fad84f5688f65053b900e59b,
title = "Potential of Intestine-Selective FXR Modulation for Treatment of Metabolic Disease",
abstract = "Farnesoid X receptor controls bile acid metabolism, both in the liver and intestine. This potent nuclear receptor not only maintains homeostasis of its own ligands, i.e., bile acids, but also regulates glucose and lipid metabolism as well as the immune system. These findings have led to substantial interest for FXR as a therapeutic target and to the recent approval of an FXR agonist for treating primary biliary cholangitis as well as ongoing clinical trials for other liver diseases. Given that FXR biology is complex, including moderate expression in tissues outside of the enterohepatic circulation, temporal expression of isoforms, posttranscriptional modifications, and the existence of several other bile acid-responsive receptors such as TGR5, clinical application of FXR modulators warrants thorough understanding of its actions. Recent findings have demonstrated remarkable physiological effects of targeting FXR specifically in the intestine (iFXR), thereby avoiding systemic release of modulators. These include local effects such as improvement of intestinal barrier function and intestinal cholesterol turnover, as well as systemic effects such as improvements in glucose homeostasis, insulin sensitivity, and nonalcoholic fatty liver disease (NAFLD). Intriguingly, metabolic improvements have been observed with both an iFXR agonist that leads to production of enteric Fgf15 and increased energy expenditure in adipose tissues and antagonists by reducing systemic ceramide levels and hepatic glucose production. Here we review the recent findings on the role of intestinal FXR and its targeting in metabolic disease.",
author = "{van Zutphen}, Tim and Anna Bertolini and {de Vries}, {Hilde D} and Bloks, {Vincent W} and {de Boer}, {Jan Freark} and Jonker, {Johan W} and Folkert Kuipers",
year = "2019",
month = "6",
day = "25",
doi = "10.1007/164_2019_233",
language = "English",
isbn = "978-3-030-22004-4",
series = "Handbook of Experimental Pharmacology",
publisher = "Springer",
pages = "207--234",
booktitle = "Bile Acids and Their Receptors",

}

RIS

TY - CHAP

T1 - Potential of Intestine-Selective FXR Modulation for Treatment of Metabolic Disease

AU - van Zutphen, Tim

AU - Bertolini, Anna

AU - de Vries, Hilde D

AU - Bloks, Vincent W

AU - de Boer, Jan Freark

AU - Jonker, Johan W

AU - Kuipers, Folkert

PY - 2019/6/25

Y1 - 2019/6/25

N2 - Farnesoid X receptor controls bile acid metabolism, both in the liver and intestine. This potent nuclear receptor not only maintains homeostasis of its own ligands, i.e., bile acids, but also regulates glucose and lipid metabolism as well as the immune system. These findings have led to substantial interest for FXR as a therapeutic target and to the recent approval of an FXR agonist for treating primary biliary cholangitis as well as ongoing clinical trials for other liver diseases. Given that FXR biology is complex, including moderate expression in tissues outside of the enterohepatic circulation, temporal expression of isoforms, posttranscriptional modifications, and the existence of several other bile acid-responsive receptors such as TGR5, clinical application of FXR modulators warrants thorough understanding of its actions. Recent findings have demonstrated remarkable physiological effects of targeting FXR specifically in the intestine (iFXR), thereby avoiding systemic release of modulators. These include local effects such as improvement of intestinal barrier function and intestinal cholesterol turnover, as well as systemic effects such as improvements in glucose homeostasis, insulin sensitivity, and nonalcoholic fatty liver disease (NAFLD). Intriguingly, metabolic improvements have been observed with both an iFXR agonist that leads to production of enteric Fgf15 and increased energy expenditure in adipose tissues and antagonists by reducing systemic ceramide levels and hepatic glucose production. Here we review the recent findings on the role of intestinal FXR and its targeting in metabolic disease.

AB - Farnesoid X receptor controls bile acid metabolism, both in the liver and intestine. This potent nuclear receptor not only maintains homeostasis of its own ligands, i.e., bile acids, but also regulates glucose and lipid metabolism as well as the immune system. These findings have led to substantial interest for FXR as a therapeutic target and to the recent approval of an FXR agonist for treating primary biliary cholangitis as well as ongoing clinical trials for other liver diseases. Given that FXR biology is complex, including moderate expression in tissues outside of the enterohepatic circulation, temporal expression of isoforms, posttranscriptional modifications, and the existence of several other bile acid-responsive receptors such as TGR5, clinical application of FXR modulators warrants thorough understanding of its actions. Recent findings have demonstrated remarkable physiological effects of targeting FXR specifically in the intestine (iFXR), thereby avoiding systemic release of modulators. These include local effects such as improvement of intestinal barrier function and intestinal cholesterol turnover, as well as systemic effects such as improvements in glucose homeostasis, insulin sensitivity, and nonalcoholic fatty liver disease (NAFLD). Intriguingly, metabolic improvements have been observed with both an iFXR agonist that leads to production of enteric Fgf15 and increased energy expenditure in adipose tissues and antagonists by reducing systemic ceramide levels and hepatic glucose production. Here we review the recent findings on the role of intestinal FXR and its targeting in metabolic disease.

U2 - 10.1007/164_2019_233

DO - 10.1007/164_2019_233

M3 - Chapter

C2 - 31236687

SN - 978-3-030-22004-4

T3 - Handbook of Experimental Pharmacology

SP - 207

EP - 234

BT - Bile Acids and Their Receptors

PB - Springer

ER -

ID: 120351531