TY - JOUR
T1 - Developments in bile salt based therapies
T2 - A critical overview
AU - Donkers, Joanne M.
AU - Roscam Abbing, Reinout L.P.
AU - van de Graaf, Konstantijn
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Bile acids, amphipathic molecules known for their facilitating role in fat absorption, are also recognized as signalling molecules acting via nuclear and membrane receptors. Of the bile acid-activated receptors, the Farnesoid X Receptor (FXR) and the G protein-coupled bile acid receptor-1 (Gpbar1 or TGR5) have been studied most extensively. Bile acid signaling is critical in the regulation of bile acid metabolism itself, but it also plays a significant role in glucose, lipid and energy metabolism. Activation of FXR and TGR5 leads to reduced hepatic bile salt load, improved insulin sensitivity and glucose regulation, increased energy expenditure, and anti-inflammatory effects. These beneficial effects render bile acid signaling an interesting therapeutic target for the treatment of diseases such as cholestasis, non-alcoholic fatty liver disease, and diabetes. Here, we summarize recent findings on bile acid signaling and discuss potential and current limitations of bile acid receptor agonist and modulators of bile acid transport as future therapeutics for a wide-spectrum of diseases.
AB - Bile acids, amphipathic molecules known for their facilitating role in fat absorption, are also recognized as signalling molecules acting via nuclear and membrane receptors. Of the bile acid-activated receptors, the Farnesoid X Receptor (FXR) and the G protein-coupled bile acid receptor-1 (Gpbar1 or TGR5) have been studied most extensively. Bile acid signaling is critical in the regulation of bile acid metabolism itself, but it also plays a significant role in glucose, lipid and energy metabolism. Activation of FXR and TGR5 leads to reduced hepatic bile salt load, improved insulin sensitivity and glucose regulation, increased energy expenditure, and anti-inflammatory effects. These beneficial effects render bile acid signaling an interesting therapeutic target for the treatment of diseases such as cholestasis, non-alcoholic fatty liver disease, and diabetes. Here, we summarize recent findings on bile acid signaling and discuss potential and current limitations of bile acid receptor agonist and modulators of bile acid transport as future therapeutics for a wide-spectrum of diseases.
KW - ASBT
KW - Bile acid
KW - FXR
KW - Metabolism
KW - NTCP
KW - TGR5
UR - http://www.scopus.com/inward/record.url?scp=85059475120&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.bcp.2018.12.018
DO - https://doi.org/10.1016/j.bcp.2018.12.018
M3 - Review article
C2 - 30582898
SN - 0006-2952
VL - 161
SP - 1
EP - 13
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
ER -