We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Recent Advances in the Digestive, Metabolic and Therapeutic Effects of Farnesoid X Receptor and Fibroblast Growth Factor 19: From Cholesterol to Bile Acid Signaling.
- Authors
Di Ciaula, Agostino; Bonfrate, Leonilde; Baj, Jacek; Khalil, Mohamad; Garruti, Gabriella; Stellaard, Frans; Wang, Helen H.; Wang, David Q.-H.; Portincasa, Piero
- Abstract
Bile acids (BA) are amphiphilic molecules synthesized in the liver (primary BA) starting from cholesterol. In the small intestine, BA act as strong detergents for emulsification, solubilization and absorption of dietary fat, cholesterol, and lipid-soluble vitamins. Primary BA escaping the active ileal re-absorption undergo the microbiota-dependent biotransformation to secondary BA in the colon, and passive diffusion into the portal vein towards the liver. BA also act as signaling molecules able to play a systemic role in a variety of metabolic functions, mainly through the activation of nuclear and membrane-associated receptors in the intestine, gallbladder, and liver. BA homeostasis is tightly controlled by a complex interplay with the nuclear receptor farnesoid X receptor (FXR), the enterokine hormone fibroblast growth factor 15 (FGF15) or the human ortholog FGF19 (FGF19). Circulating FGF19 to the FGFR4/β-Klotho receptor causes smooth muscle relaxation and refilling of the gallbladder. In the liver the binding activates the FXR-small heterodimer partner (SHP) pathway. This step suppresses the unnecessary BA synthesis and promotes the continuous enterohepatic circulation of BAs. Besides BA homeostasis, the BA-FXR-FGF19 axis governs several metabolic processes, hepatic protein, and glycogen synthesis, without inducing lipogenesis. These pathways can be disrupted in cholestasis, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Thus, targeting FXR activity can represent a novel therapeutic approach for the prevention and the treatment of liver and metabolic diseases.
- Subjects
LIVER physiology; FIBROBLAST growth factors; DIGESTIVE system diseases; CHOLESTASIS; CELL receptors; NON-alcoholic fatty liver disease; CELLULAR signal transduction; METABOLIC disorders; LIVER diseases; BILE acids; DIGESTION; GALLBLADDER; GLYCOGEN; CHOLESTEROL; HEPATOCELLULAR carcinoma
- Publication
Nutrients, 2022, Vol 14, Issue 23, p4950
- ISSN
2072-6643
- Publication type
Article
- DOI
10.3390/nu14234950