Repurposed Drug Helps Obese Mice Lose Weight

An off-label experiment in mice using disulfiram, which has been used to treat alcohol-use disorder for more than 50 years, consistently normalized body weight and reversed metabolic damage in obese middle-age mice of both sexes. 

The international study was led by researchers at NIA. Results were published online May 14 in the journal Cell Metabolism.

The scientific team studied groups of 9-month-old lab mice who had been fed a high-fat diet for 12 weeks. As expected, this diet made the mice overweight and they started to show signs of pre-diabetes-like metabolic problems, such as insulin resistance and elevated fasting blood sugar levels. 

Next, the scientists divided these mice into 4 groups to be fed 4 different diets for an additional 12 weeks: a standard diet alone, a high-fat diet alone, a high-fat diet with a low amount of disulfiram, or a high-fat diet with a higher amount of disulfiram. 

As expected, the mice who stayed on the high-fat diet alone continued to gain weight and show metabolic problems. Mice who switched to standard diet alone gradually saw their body weight, fat composition and blood sugar levels return to normal.

The mice in the remaining two groups, with either a low or high dose of disulfiram added to their still-fatty food, showed a dramatic decrease in their weight and related metabolic damage. 

Disulfiram treatment, which has few harmful side effects in humans, also appeared to protect the pancreas and liver from damage caused by pre-diabetic type metabolic changes and fat build-up usually caused by eating a high-fat diet.

The NIA scientists, Drs. Michel Bernier and Rafael de Cabo, collaborate frequently with researchers at NIH and beyond on studies into how changes in dietary patterns such as intermittent fasting could lead to cognitive and physical health benefits. They first became interested in disulfiram after reading about the benefits this class of drug has shown in treating type 2 diabetes in rats, coupled with the growing interest in repurposing drugs that may also improve healthy aging.

“When we first went down this path, we did not know what to expect, but once we started to see data showing dramatic weight loss and leaner body mass in the mice, we turned to each other and couldn’t quite believe our eyes,” Bernier said.