| Summary: | Apart from well-known functions of bile acids in digestion and solubilization of lipophilic
nutrients and drugs in the small intestine, the emerging evidence from the past two
decades identified the role of bile acids as signaling, endocrine molecules that regulate
the glucose, lipid, and energy metabolism through complex and intertwined pathways
that are largely mediated by activation of nuclear receptor farnesoid X receptor (FXR)
and cell surface G protein-coupled receptor 1, TGR5 (also known as GPBAR1).
Interactions of bile acids with the gut microbiota that result in the altered composition
of circulating and intestinal bile acids pool, gut microbiota composition and modified
signaling pathways, are further extending the complexity of biological functions of these
steroid derivatives. Thus, bile acids signaling pathways have become attractive targets
for the treatment of various metabolic diseases and metabolic syndrome opening the
new potential avenue in their treatment. In addition, there is a significant effort to
unveil some specific properties of bile acids relevant to their intrinsic potency and
selectivity for particular receptors and to design novel modulators of these receptors with
improved pharmacokinetic and pharmacodynamic profiles. This resulted in synthesis
of few semi-synthetic bile acids derivatives such as 6a-ethyl-chenodeoxycholic acid
(obeticholic acid, OCA), norursodeoxycholic acid (norUDCA), and 12-monoketocholic
acid (12-MKC) that are proven to have positive effect in metabolic and hepato-biliary
disorders. This review presents an overview of the current knowledge related to bile
acids implications in glucose, lipid and energy metabolism, as well as a potential
application of bile acids in metabolic syndrome treatment with future perspectives.
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