Abstract
Bile acids (BA) are classically known as an important agent in lipid absorption and cholesterol metabolism. Nowadays, their role in glucose regulation and energy homeostasis are widely reported. BAs are involved in various cellular signaling pathways, such as protein kinase cascades, cyclic AMP (cAMP) synthesis, and calcium mobilization. They are ligands for several nuclear hormone receptors, including farnesoid X-receptor (FXR). Recently, BAs have been shown to bind to muscarinic receptor and Takeda G-protein-coupled receptor 5 (TGR5), both G-protein-coupled receptor (GPCR), independent of the nuclear hormone receptors. Moreover, BA signals have also been elucidated in other nonclassical BA pathways, such as sphingosine-1-posphate and BK (large conductance calcium- and voltage activated potassium) channels. Hydrophobic BAs have been proven to affect heart rate and its contraction. Elevated BAs are associated with arrhythmias in adults and fetal heart, and altered ratios of primary and secondary bile acid are reported in chronic heart failure patients. Meanwhile, in patients with liver cirrhosis, cardiac dysfunction has been strongly linked to the increase in serum bile acid concentrations. In contrast, the most hydrophilic BA, known as ursodeoxycholic acid (UDCA), has been found to be beneficial in improving peripheral blood flow in chronic heart failure patients and in protecting the heart against reperfusion injury. This review provides an overview of BA signaling, with the main emphasis on past and present perspectives on UDCA signals in the heart.
Highlights
Bile acids (BAs) are derived from cholesterol and are stored in the gall bladder
Ursodeoxycholic acid is synthesized by dehydroxylation of free bile acid chenodeoxycholic acid (CDCA)
Ursodeoxycholic acid has been shown to inhibit the effect of bilirubin- and lithocholic acid (LCA)-induced apoptosis in osteoblastic cells by preventing translocation of pro-apoptotic protein Bax to mitochondria and downregulating caspase-3 activity
Summary
Bile acids (BAs) are derived from cholesterol and are stored in the gall bladder. Cholic acid (CA) and chenodeoxycholic acid (CDCA) are the two most common types of primary bile acids, which are synthesized in the liver and conjugated to either taurine or glycine. The most common secondary bile acids—deoxycholic acid (DCA) and lithocholic acid (LCA)—are synthesized by microbial flora of the small intestine. These two bile acids are produced as a result of deconjugation and dehydroxylation of primary. Ursodeoxycholic acid is synthesized by dehydroxylation of free bile acid CDCA It is the most hydrophilic bile acid, and small amounts of it can be found in the feces. The BA pool circulates in humans through enterohepatic circulation This enterohepatic circulation involves liver as the main organ, gallbladder as a storage organ for the bile, and the small intestine to help in digestion of fats as well as excretion and reabsorption. Our review aims to give an overview of general bile acids signaling with an emphasis on the most hydrophilic BA signals in the heart
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