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Bile Acids and Their Receptors pp 73–93Cite as

The Enterokine Fibroblast Growth Factor 15/19 in Bile Acid Metabolism

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 256))

Abstract

The endocrine fibroblast growth factors (FGFs), FGF19, FGF21, and FGF23, play a key role in whole-body homeostasis. In particular, FGF19 is a postprandial hormone regulating glucose homeostasis, glycogen and protein synthesis, and primary bile acid (BA) metabolism. In the ileum, BA-dependent farnesoid X receptor (FXR) activation induces the production of FGF19, which reaches the liver through the portal system where it represses the expression of CYP7A1, the rate-limiting enzyme of hepatic de novo BAs synthesis. Dysregulation of BA levels associated with alteration in FGF19 level has been depicted in different pathological conditions of the gut-liver axis. Furthermore, FGF19 exploits strong anti-cholestatic and anti-fibrotic activities in the liver. However, native FGF19 seems to retain peculiar hepatic pro-tumorigenic actions. Recently engineered FGF19 analogues have been recently synthetized, with fully retained BA regulatory activity but without intrinsic pro-tumoral action, thus opening bona fide novel pharmacological strategy for the treatment of gut-liver axis diseases.

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Authors and Affiliations

  1. Department of Interdisciplinary Medicine, “Aldo Moro” University of Bari, Bari, Italy

    Marica Cariello, Marilidia Piglionica, Raffaella Maria Gadaleta & Antonio Moschetta

  2. National Cancer Center, IRCCS Istituto Tumori “Giovanni Paolo II”, Bari, Italy

    Antonio Moschetta

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  1. Marica Cariello
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  2. Marilidia Piglionica
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  3. Raffaella Maria Gadaleta
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  4. Antonio Moschetta
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  1. University of Perugia, School of Medicine, Perugia, Italy

    Stefano Fiorucci

  2. S.C. Gastroenterologia, Azienda Ospedaliera di Perugia, Perugia, Italy

    Eleonora Distrutti

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Cariello, M., Piglionica, M., Gadaleta, R.M., Moschetta, A. (2019). The Enterokine Fibroblast Growth Factor 15/19 in Bile Acid Metabolism. In: Fiorucci, S., Distrutti, E. (eds) Bile Acids and Their Receptors. Handbook of Experimental Pharmacology, vol 256. Springer, Cham. https://doi.org/10.1007/164_2019_235

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