Article ; Online: Bile salt signaling and bile salt-based therapies in cardiometabolic disease.
Clinical science (London, England : 1979)
2024 Volume 138, Issue 1, Page(s) 1–21
Abstract: Bile salts have an established role in the emulsification and intestinal absorption of dietary lipids, and their homeostasis is tightly controlled by various transporters and regulators in the enterohepatic circulation. Notably, emerging evidence points ... ...
| Abstract | Bile salts have an established role in the emulsification and intestinal absorption of dietary lipids, and their homeostasis is tightly controlled by various transporters and regulators in the enterohepatic circulation. Notably, emerging evidence points toward bile salts as major modulators of cardiometabolic disease (CMD), an umbrella disease of disorders affecting the heart and blood vessels that is caused by systemic metabolic diseases such as Type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD), the latter encompassing also metabolic dysfunction-associated steatohepatitis (MASH). The underlying mechanisms of protective effects of bile salts are their hormonal properties, enabling them to exert versatile metabolic effects by activating various bile salt-responsive signaling receptors with the nuclear farnesoid X receptor (FXR) and the Takeda G-protein-coupled receptor 5 (TGR5) as most extensively investigated. Activation of FXR and TGR5 is involved in the regulation of glucose, lipid and energy metabolism, and inflammation. Bile salt-based therapies directly targeting FXR and TGR5 signaling have been evaluated for their therapeutic potential in CMD. More recently, therapeutics targeting bile salt transporters thereby modulating bile salt localization, dynamics, and signaling, have been developed and evaluated in CMD. Here, we discuss the current knowledge on the contribution of bile salt signaling in the pathogenesis of CMD and the potential of bile salt-based therapies for the treatment of CMD. |
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| MeSH term(s) | Humans ; Diabetes Mellitus, Type 2/drug therapy ; Signal Transduction ; Bile Acids and Salts ; Energy Metabolism ; Fatty Liver ; Membrane Transport Proteins ; Cardiovascular Diseases/drug therapy |
| Chemical Substances | Bile Acids and Salts ; Membrane Transport Proteins |
| Language | English |
| Publishing date | 2024-01-05 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 206835-7 |
| ISSN | 1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221 |
| ISSN (online) | 1470-8736 |
| ISSN | 0301-0538 ; 0009-0360 ; 0143-5221 |
| DOI | 10.1042/CS20230934 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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