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Ursodeoxycholic acid is a GPBAR1 agonist and resets liver/intestinal FXR signaling in a model of diet-induced dysbiosis and NASH.

Author: BiagioliMichele, CarinoAdriana, DistruttiEleonora, FiorucciChiara, FiorucciStefano, MarchianòSilvia, MontiMaria Chiara, RicciPatrizia, ScarpelliPaolo, ZampellaAngela

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Overview

Obeticholic acid (OCA) is an effective treatment for NASH, but it has major side effects, including pruritus and an increased risk of liver decompensation in cirrhotic patients. Ursodeoxycholic acid (UDCA) is a safe and inexpensive bile acid used to treat liver disorders, but its mechanism of action is poorly understood. This study compared the effects of OCA and UDCA in a mouse model of NASH. Both OCA and UDCA effectively prevented body weight gain, insulin resistance, and elevated AST plasma levels in mice fed a high-fat/cholesterol and fructose diet. Both compounds also prevented liver steatosis, inflammation, and fibrosis. UDCA effectively activated GPBAR1, a receptor involved in bile acid metabolism, in vitro. RNA sequencing analysis showed that UDCA and OCA modulated different genes, suggesting that they exert beneficial effects through distinct pathways.
Paper Details　
Original Abstract of the Article :
Obeticholic acid (OCA) is a farnesoid-X-receptor (FXR) ligand, shown effective in reducing steatosis and fibrosis in NASH patients. However, OCA causes major side effects including pruritus, while increases the risk for liver decompensation in cirrhotic patients. Ursodeoxycholic acid (UDCA), is a sa...See full text at original site
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引用元：
https://doi.org/10.1016/j.bbalip.2019.07.006

データ提供：米国国立医学図書館（NLM）

Ursodeoxycholic Acid as a GPBAR1 Agonist in a Model of NASH

This study, exploring the complex world of liver disease, investigates the potential therapeutic effects of ursodeoxycholic acid (UDCA), a bile acid, in a mouse model of non-alcoholic steatohepatitis (NASH). The study aimed to determine the mechanism of action of UDCA and compare its effects to those of obeticholic acid (OCA), a known farnesoid-X-receptor (FXR) ligand, in preventing the development of NASH. This research is crucial in the search for effective and safe treatments for NASH, a growing public health concern.

UDCA: A Promising Therapeutic Agent for NASH

The study revealed that UDCA, a safe and widely used bile acid, effectively prevented the development of NASH in mice, comparable to the effects of OCA. Interestingly, UDCA was found to be a GPBAR1 ligand, activating a distinct pathway from OCA's FXR activation. This finding is significant, as it suggests that UDCA's beneficial effects in NASH are mediated through a different mechanism than previously thought, potentially offering a more targeted and potentially safer therapeutic approach.

Exploring Novel Therapeutic Strategies for NASH

This study highlights the importance of exploring alternative therapeutic targets for NASH, beyond FXR activation. The finding that UDCA is a GPBAR1 agonist opens up new avenues for research and development of novel therapeutic agents for NASH, potentially offering a wider range of treatment options.

Dr.Camel's Conclusion

The world of liver disease is a vast and complex one, but researchers are tirelessly seeking effective treatments to improve patient outcomes. This study is a testament to their dedication, highlighting the potential of UDCA as a therapeutic agent for NASH. It reminds us that the search for effective treatments for this growing public health concern is ongoing and that new discoveries can offer hope for the future. Just as a camel adapts to the harsh conditions of the desert, researchers are adapting their approaches to find solutions to complex medical challenges.

Date :
  1. Date Completed 2020-03-06
  2. Date Revised 2020-03-06
Further Info :

Pubmed ID

31325638

DOI: Digital Object Identifier

10.1016/j.bbalip.2019.07.006

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Languages

English

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