Overview of Bile Acids Signaling and Perspective on the Signal of Ursodeoxycholic Acid, the Most Hydrophilic Bile Acid, in the Heart

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.

Mechanisms of Interactions between Bile Acids and Plant Compounds—A Review

“…The most common secondary bile acids, resulting from deconjugation and dehydroxylation of primary bile acids, are desoxycholic acid (DCA) and lithocholic acid (LCA) [23]. Due to its hydrophobicity, reabsorption rates into the enterohepatic circulation are small for LCA [24]. On the other hand, DCA is reabsorbed in the colon and accumulates in the bile acid pool [17].…”

“…The amphiphilic character of bile acids is explained by their rigid steroid backbone containing methyl groups oriented towards a hydrophobic face, whereas the hydroxyl groups and the amino group (taurine or glycine) are oriented towards a hydrophilic face [25]. Due to their varying hydroxylation, bile acids differ in hydrophobicity, which decreases in the order of LCA > DCA > CDCA > CA [24]. By the action of anaerobic microbiota, primary bile acids are converted into secondary and tertiary bile acids.…”

“…Changes in the bile acid pool are linked to cardiac dysfunctions, liver diseases, biliary stones development, and diabetes. Inflammation, apoptosis, and cell death may be caused by cytotoxicity induced by microbial changes of bile acid structures [17,24,122,123]. Hydrophobicity is an important determinant of the cytotoxicity of bile acids [124].…”

Bile salts in digestion and transport of lipids

“…BS and BA have a wide range of functions, from emulsification of dietary lipids, and facilitating their digestion and absorption, to signal transduction in cell proliferation, metabolism, and differentiation [27]. As a direct mode of action, BS form mixed micelles, which aids in the absorption of lipolysis products and lipid-soluble vitamins.…”

Bile Acids in Patients with Uncontrolled Type 2 Diabetes Mellitus – The Effect of Two Days of Oatmeal Treatment

“…However, the fermentation of dietary fibres by the gut microbiota may partly liberate the bound BAs and the drop in pH that is associated with the fermentation process decreases the activity of the enzyme 7 α-dehydroxylase which catalyses the conversion of primary to secondary BAs [21]. While some secondary BAs like DCA or LCA have been associated with negative effects on health [22] others like UDCA show beneficial effects [23,24]. In our study, we observed a significant decrease in total BA under the oatmeal treatment as compared to the control treatment, similar like it was reported by Gunness et al in pigs [25].…”