Back to Search
Start Over
The Role of the Nuclear Receptor FXR in Arsenic-Induced Glucose Intolerance in Mice.
- Source :
- Toxics; Oct2023, Vol. 11 Issue 10, p833, 16p
- Publication Year :
- 2023
-
Abstract
- Inorganic arsenic in drinking water is prioritized as a top environmental contaminant by the World Health Organization, with over 230 million people potentially being exposed. Arsenic toxicity has been well documented and is associated with a plethora of human diseases, including diabetes, as established in numerous animal and epidemiological studies. Our previous study revealed that arsenic exposure leads to the inhibition of nuclear receptors, including LXR/RXR. To this end, FXR is a nuclear receptor central to glucose and lipid metabolism. However, limited studies are available for understanding arsenic exposure-FXR interactions. Herein, we report that FXR knockout mice developed more profound glucose intolerance than wild-type mice upon arsenic exposure, supporting the regulatory role of FXR in arsenic-induced glucose intolerance. We further exposed mice to arsenic and tested if GW4064, a FXR agonist, could improve glucose intolerance and dysregulation of hepatic proteins and serum metabolites. Our data showed arsenic-induced glucose intolerance was remarkably diminished by GW4064, accompanied by a significant ratio of alleviation of dysregulation in hepatic proteins (83%) and annotated serum metabolites (58%). In particular, hepatic proteins "rescued" from arsenic toxicity by GW4064 featured members of glucose and lipid utilization. For instance, the expression of PCK1, a candidate gene for diabetes and obesity that facilitates gluconeogenesis, was repressed under arsenic exposure in the liver, but revived with the GW4064 supplement. Together, our comprehensive dataset indicates FXR plays a key role and may serve as a potential therapeutic for arsenic-induced metabolic disorders. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 23056304
- Volume :
- 11
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Toxics
- Publication Type :
- Academic Journal
- Accession number :
- 173338100
- Full Text :
- https://doi.org/10.3390/toxics11100833