What is Farnesoid X receptor agonist?
Farnesoid X Receptor (FXR), a metabolic nuclear receptor, are found to be activated by primary BAs such as chenodeoxycholic acid (CDCA), cholic acid (CA) and synthetic agonists such as obeticholic acid (OCA).
Where is the Farnesoid X receptor?
liver
Farnesoid X receptor (FXR) is a nuclear hormone receptor with high expression in liver. It regulates many genes involved in lipid and glucose metabolism, liver regeneration, inflammation, and liver cancer (Wang et al., 2008; Modica et al., 2008).
How the Farnesoid receptor plays a role in the gastrointestinal tract?
The bile-acid-activated nuclear receptor, farnesoid X receptor (FXR), plays a pivotal role in regulating bile acid, lipid and glucose homeostasis as well as in regulating the inflammatory responses, barrier function and prevention of bacterial translocation in the intestinal tract.
What is the function of FXR?
FXR regulates a large number of target genes involved in bile acid, lipoprotein and glucose metabolisms. FXR binds to DNA either as a heterodimer with RXR or as a monomer to regulate the expression of various genes. Analyses of FXR knockout animals also reveal an unexpected role of FXR in lipid metabolism.
What are FXR agonists used for?
FXR agonists are an attractive class of drugs for patients with chronic liver diseases. In addition to their critical role in regulating BA, carbohydrate, and lipid metabolism, they also possess potent anti-inflammatory and anti-fibrotic properties.
Is UDCA an FXR agonist?
BAs suppress CYP7A1 via hepatic FXR/SHP and intestinal FXR/FGF19 signaling pathways [23]. However, UDCA, which constituted almost 90% of BAs in our patients, has only low affinity for and hence no agonistic activity on FXR [24–28].
What do nuclear receptors do?
Nuclear receptors have the ability to directly bind to DNA and regulate the expression of adjacent genes; hence these receptors are classified as transcription factors. As a consequence, nuclear receptors play key roles in both embryonic development and adult homeostasis.
Where does ursodeoxycholic acid come from?
Ursodeoxycholic acid (UDCA), also known as ursodiol, is a secondary bile acid, produced in humans and most other species from metabolism by intestinal bacteria. It is synthesized in the liver in some species, and was first identified in bear bile, which is the derivation of its name Ursus.
What is HD FXR?
The FXR was the base model with solid black paint and laced wheels. The FXRS was the deluxe model with two tone paint, mag wheels and a backrest. The FXR chassis was essentially an FLT Tour Glide chassis with slightly bigger diameter frame tubes and a more conventional design around the steering head.
What is FXR Signalling?
FXR is highly expressed in the liver and gut, relative to other tissues, and contributes to the maintenance of cholesterol/bile acid homeostasis by regulating a variety of metabolic enzymes and transporters. FXR activation also affects lipid and glucose metabolism, and can influence drug metabolism.
What is the full form of FXR?
The bile acid receptor (BAR), also known as farnesoid X receptor (FXR) or NR1H4 (nuclear receptor subfamily 1, group H, member 4), is a nuclear receptor that is encoded by the NR1H4 gene in humans.
Where is the farnesoid X receptor located in the body?
Farnesoid X receptor (FXR) is a bile acid activated nuclear receptor (BAR) and is mainly expressed in the liver and intestine. Upon ligand binding, FXR regulates key genes involved in the metabolic process of bile acid synthesis, transport and reabsorption and is also involved in the metabolism of carbohydrates and lipids.
How is the farnesoid X receptor activated by bile acids?
Activation of the farnesoid X receptor (FXR) by bile acids increases expression of ABCB4 in primary human hepatocytes treated with FXR agonists via direct binding of FXR/retinoid X receptor (RXR) heterodimer to an FXR response element at the distal promoter (-1970 to -1958) (Huang et al. 2003).
What happens to the farnesoid X receptor knockout mice?
FXR knockout mice showed sustained activation of the Wnt/β-catenin pathway, in which the tumor suppressor gene N-myc downstream-regulated gene 2 was reduced, and spontaneously develop HCC and other cancers.
Which is a natural ligand for the FXR receptor?
Chenodeoxycholic acid and other bile acids are natural ligands for FXR. Similar to other nuclear receptors, when activated, FXR translocates to the cell nucleus, forms a dimer (in this case a heterodimer with RXR) and binds to hormone response elements on DNA, which up- or down-regulates the expression of certain genes.