|NCI's Frank Gonzalez|
Investigators at Penn State say they may be on track to identifying a new metabolic drug with potential for fatty liver disease, diabetes and obesity.
The team zeroed in on a bile acid--glycine-beta muricholic acid, or Gly-MCA--that was able in pill form to inhibit a transcription factor called farnesoid X receptor (FXR), which in turn regulates bile acids, fats and glucose.
"Depending on the balance of conjugated and unconjugated bile acids, bacteria can modify these bile acid pools and turn off or turn on this receptor--FXR--in the gut," said Frank Gonzalez, chief of the laboratory of metabolism at the National Cancer Institute.
The researchers spent considerable time searching for the right bile acid that could survive enzymatic activity in the gut. And they say that their oral drug looked promising when tested in mice. Their results were published in Nature Communications.
There's plenty more work to be done. The researchers are still searching for the right drug that would prove most effective. And they say there's more work ahead on animal studies before they start to think how the treatment could be tested in humans.
"Ideally what we would like to do is start looking at whether we can improve upon the current molecule to make more effective derivatives of Gly-MCA that are more resistant to bacterial hydrolyses and more potent at selectively inhibiting FXR," said Andrew Patterson, associate professor of molecular toxicology, Penn State.