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Int J Mol Sci. 2018 Jul 16;19(7). pii: E2069. doi: 10.3390/ijms19072069.

Update on FXR Biology: Promising Therapeutic Target?

Author information

1
Department of Pharmacology, School of Medicine, Wonkwang University, 460 Iksandae-ro, Iksan 54538, Jeonbuk, Korea. hancy17@wku.ac.kr.

Abstract

Farnesoid X receptor (FXR), a metabolic nuclear receptor, plays critical roles in the maintenance of systemic energy homeostasis and the integrity of many organs, including liver and intestine. It regulates bile acid, lipid, and glucose metabolism, and contributes to inter-organ communication, in particular the enterohepatic signaling pathway, through bile acids and fibroblast growth factor-15/19 (FGF-15/19). The metabolic effects of FXR are also involved in gut microbiota. In addition, FXR has various functions in the kidney, adipose tissue, pancreas, cardiovascular system, and tumorigenesis. Consequently, the deregulation of FXR may lead to abnormalities of specific organs and metabolic dysfunction, allowing the protein as an attractive therapeutic target for the management of liver and/or metabolic diseases. Indeed, many FXR agonists have been being developed and are under pre-clinical and clinical investigations. Although obeticholic acid (OCA) is one of the promising candidates, significant safety issues have remained. The effects of FXR modulation might be multifaceted according to tissue specificity, disease type, and/or energy status, suggesting the careful use of FXR agonists. This review summarizes the current knowledge of systemic FXR biology in various organs and the gut⁻liver axis, particularly regarding the recent advancement in these fields, and also provides pharmacological aspects of FXR modulation for rational therapeutic strategies and novel drug development.

KEYWORDS:

FXR (farnesoid X receptor); liver diseases; metabolic disorders; nuclear receptor; pharmacological application

PMID:
30013008
PMCID:
PMC6073382
DOI:
10.3390/ijms19072069
[Indexed for MEDLINE]
Free PMC Article

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