Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance
By S. Fang, J. M. Suh, Shannon M. Reilly, Elizabeth Yu, O. Osborn, D. Lackey, E. Yoshihara, A. Perino, Sandra H. Jacinto, Yelizaveta Lukasheva and 12 more. Nature Medicine, 2015
677 citations recorded by the source corpus.
The systemic expression of the bile acid (BA) sensor farnesoid X receptor (FXR) has led to promising new therapies targeting cholesterol metabolism, triglyceride production, hepatic steatosis and biliary cholestasis. In contrast to systemic therapy, bile acid release during a meal selectively activates intestinal FXR. By mimicking this tissue-selective effect, the gut-restricted FXR agonist fexaramine (Fex) robustly induces enteric fibroblast growth factor 15 (FGF15), leading to alterations in BA composition, but does so without activating FXR target genes in the liver. However, unlike systemic agonism, we find that Fex reduces diet-induced weight gain, body-wide inflammation and hepatic glucose production, while enhancing thermogenesis and browning of white adipose tissue (WAT). These pronounced metabolic improvements suggest tissue-restricted FXR activation as a new approach in the treatment of obesity and metabolic syndrome.
Subfields: Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/2ed108da2aec6e2c21ee4afb5c9450c524c67cc4
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In Molecular Biology
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In Oncology
Citations in the corpus
- Mechanisms and disease consequences of nonalcoholic fatty liver disease (2021, background): “, 2019), and, FXR agonism in the intestine may contribute to its overall therapeutic benefit (Fang et al., 2015).”
- Brown and beige fat: Physiological roles beyond heat-generation (2015, background): “, 2012), FXR agonist fexaramine (Fang et al., 2015), soluble guanylyl cyclase (Hoffmann et al.”
- Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism. (2016, neutral): “browning of adipose tissue (Fang et al., 2015).”