TY - JOUR
T1 - Enterohepatic and non-canonical roles of farnesoid X receptor in controlling lipid and glucose metabolism
AU - Zhou, Weinan
AU - Anakk, Sayeepriyadarshini
N1 - This work was supported by start-up funds from the University of Illinois at Urbana-Champaign and seed grant from Cancer center of Illinois , (to S.A.), R01 DK113080 (to S.A.), and R01 DK130317 (to S.A.) from NIDDK .
PY - 2022/6/1
Y1 - 2022/6/1
N2 - Farnesoid X receptor (FXR) is a nuclear receptor that transcriptionally regulates bile acid homeostasis along with nutrient metabolism. In addition to the gastrointestinal (GI) tract, FXR expression has been widely noted in kidney, adrenal gland, pancreas, adipose, skeletal muscle, heart, and brain. Except for the liver and gut, the relevance of FXR signaling in metabolism in other tissues remains poorly understood. This review examines the classical and non-canonical tissue-specific roles of FXR in regulating, lipids, and glucose homeostasis under normal and diseased states. FXR activation has been reported to be protective against cholestasis, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), type 2 diabetes, cardiovascular and kidney diseases. Several ongoing clinical trials are investigating FXR ligands as a therapeutic target for primary biliary cholangitis (PBC) and NASH, which substantiate the significance of FXR signaling in modulating metabolic processes. This review highlights that FXR ligands, albeit an attractive therapeutic target for treating metabolic diseases, tissue-specific modulation of FXR may be the key to overcoming some of the adverse clinical effects.
AB - Farnesoid X receptor (FXR) is a nuclear receptor that transcriptionally regulates bile acid homeostasis along with nutrient metabolism. In addition to the gastrointestinal (GI) tract, FXR expression has been widely noted in kidney, adrenal gland, pancreas, adipose, skeletal muscle, heart, and brain. Except for the liver and gut, the relevance of FXR signaling in metabolism in other tissues remains poorly understood. This review examines the classical and non-canonical tissue-specific roles of FXR in regulating, lipids, and glucose homeostasis under normal and diseased states. FXR activation has been reported to be protective against cholestasis, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), type 2 diabetes, cardiovascular and kidney diseases. Several ongoing clinical trials are investigating FXR ligands as a therapeutic target for primary biliary cholangitis (PBC) and NASH, which substantiate the significance of FXR signaling in modulating metabolic processes. This review highlights that FXR ligands, albeit an attractive therapeutic target for treating metabolic diseases, tissue-specific modulation of FXR may be the key to overcoming some of the adverse clinical effects.
KW - Bile acids
KW - FXR
KW - Glucose homeostasis
KW - Lipid metabolism
KW - Non-enterohepatic tissues
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U2 - 10.1016/j.mce.2022.111616
DO - 10.1016/j.mce.2022.111616
M3 - Article
C2 - 35304191
AN - SCOPUS:85126900225
SN - 0303-7207
VL - 549
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
M1 - 111616
ER -