Experimental anti-obesity drug reduces gut inflammation in mice
An experimental anti-obesity drug developed several years ago by researchers at the Salk Institute has been found to prevent intestinal inflammation in mice. The drug has yet to be tested in humans but the findings point to a novel way to prevent flare-ups in patients suffering from inflammatory bowel disease (IBD).
Farnesoid X receptor (FXR) is a protein expressed in the liver and intestine. When we start eating a meal, and bile acids begin to build up, FXR triggers a variety of metabolic processes to aid digestion and regulate blood sugar.
Ronald Evans, from Salk’s Gene Expression Laboratory, worked with colleagues back in 2015 to develop a drug designed specifically to activate FXR in the gut. The idea was if FXR could be triggered in the intestines in the absence of eating food, then the body could be tricked into stepping up its fat-burning processes.
The drug, called fexaramine, was incredibly effective at inducing weight loss in obese mice. To date, the drug has yet to be tested in humans.
This latest research from Evans and colleagues at Salk looks at the role FXR plays in regulating gut inflammation. The hypothesis tested was based on the idea FXR activation could help suppress inflammatory processes that take place during feeding. So it was plausible to presume fexaramine may reduce intestinal inflammation.
“Every time you eat, you’re causing small amounts of inflammation in your gut as your intestinal cells encounter new molecules," said Michael Downes, co-corresponding author on the new study. "FXR makes sure inflammation stays under control during normal feeding."
Using an updated iteration of fexaramine, dubbed FexD, the researchers found gut inflammation in mouse models of IBD could be effectively treated. The drug worked both as a preventative agent, before inflammation came on, and as a treatment given after the onset of inflammation.
“The Salk-developed drug FexD provides a new way to restore balance to the digestive system and treat inflammatory diseases that are currently very difficult to manage,” said Evans, senior author on the new study.
It's early days for the research, and more work is needed before human trials can take place. The researchers suggest the drug can be optimized for safety and efficacy in humans, and then human tests can begin.
The new study was published in PNAS.