One Step Closer

Receptor may be key to treating nonalcoholic fatty liver disease.

Inhibiting a nuclear receptor in the gut could lead to a treatment for a liver disorder that affects almost 30 percent of the Western world’s adult population, according to an international team of researchers.

The researchers found that tempol, an antioxidant drug, and antibiotics can treat and prevent nonalcoholic fatty liver disease in mice that were fed a high-fat diet. Nonalcoholic fatty liver disease—NAFLD—is a buildup of fat in liver cells that disrupts liver function and, if left untreated, can lead to liver failure.

“The effects of this disease are staggering in the United States and around the world,” said Andrew Patterson, assistant professor of molecular toxicology. “Some patients with NAFLD can develop a range of health problems, such as steatohepatitis, fibrosis, and cirrhosis, that, if it gets this far, may require a liver transplant.”

Patterson said that, according to this study and earlier research, tempol and antibiotics appear to reduce some types of Lactobacillus—an intestinal bacteria that converts lactose and other sugars into lactic acid. When Lactobacillus levels decrease, a bile acid—tauro-beta-muricholic acid—increases. The increase of this bile acid then directly inhibits the intestinal farnesoid X receptor (FXR), which regulates the metabolism of bile acids, fats, and glucose in the body.

“What is exciting about this study, in particular, is that we feel like we are taking another small step in shedding some light on how diet and drugs can modulate bacteria and how these organisms modify their environment,” said Patterson. “But we are proceeding cautiously. It’s very easy to overhype this type of research, as we feel the research is just in its infancy.”

—Matt Swayne