Farnesoid X receptor (FXR
is the bridge between the liver and the small intestine to control BA levels and regulate BA synthesis." (4) By doing so it regulates glucose, lipoproteins, lipid metabolism, inflammation, tumor suppression, drug metabolism, hepatic regeneration, fibrosis, cell differentiation and neoplasia.
Further, this non-bile acid class contains steroidal and non-steroidal components and does not contain the carboxylic acid group that can lead to the formation of taurine and glycine conjugates normally associated with bile acids, which may also be present in other classes of FXR
A regulatory cascade of the nuclear receptors FXR
, SHP-1, and LRH-1 represses bile acid biosynthesis.
RXRA, which encodes retinoid X receptor-a ( RXR-a ), serves as a common heterodimeric partner for a number of nuclear receptors, including PPARs, LXRs, FXRs
, and VDRs .
To address the molecular mechanisms underlying the function of VSG in effectively inducing weight loss and diabetes symptom resolution, we predicted the musculoaponeurotic fibrosarcoma oncogene family B (MAFB) as one of the candidate transcription factors that might bind FXR
promoter through bioinformatics analysis using JASPAR.
Stimulation of the farnesoid X receptor (FXR
) initiates the production of fibroblastic growth factor 15/19 (FGF-15/19) that interacts in the hepatocytes with cholesterol 7 alpha-hydroxylase (CYP7A/1) and reduces BA synthesis, with a negative feedback mechanism.
Abbreviations ACLF: Acute-on-chronic liver failure PRR: Pattern recognition receptor IL: Interleukin TNF: Tumor necrosis factor NLR: Nucleotide-binding oligomerization domain (NOD-) like receptor TLR: Toll-like receptor PAMPs: Pathogen-associated molecular patterns DAMPs: Damage/danger-associated molecular patterns SASP: Senescence-associated secretory phenotype FXR
: Farnesoid-X-receptor EASL-CLIF: European Association for the Study of the Liver-Consortium on Chronic Liver Insufficiency.
More specifically, intestinal dysbiosis resulting in higher levels of unconjugated bile acid, able to inhibit farnesoid X receptor (FXR
) signaling, was observed in animal models .
Moreover, liver inflammation was most pronounced in Western diet-fed male mice that also lacked farnesoid x receptor (FXR
), a bile acid receptor.
Allergan has entered into a clinical trial agreement with Novartis to conduct a Phase lib study, using Allergan's cenicriviroc (CVC) and Novartis'lead FXR
agonist for the treatment of non-alcoholic steatohepatitis (NASH).
Clemmensen et al., "FXR
is a molecular target for the effects of vertical sleeve gastrectomy," Nature, vol.
ADMSC: adipose mesenchymal stem cell; PC1: Prohormone Convertase 1; ILC-2: group 2 innate lymphoid cells; BMP7: bone morphogenic protein 7; M2 ATM: adipose tissue macrophage 2; FGF21: fibroblastic growth factor 21; PPARy: peroxisome proliferator-activated receptor gamma; TR: thyroid receptors; FXR
: farnesoid X receptor; BNP: brain natriuretic factor.