Repurposed drug helps obese mice lose weight, improve metabolic function

Thursday, May 14, 2020

Treatment with disulfiram, normally prescribed to treat alcohol use disorder, shows health benefits in animal study

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-aged mice of both sexes. The international study was led by researchers at the National Institute on Aging (NIA), part of the National Institutes of Health . The results were published online in the journal Cell Metabolism on May 14.

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 four groups to be fed four 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. Mice on the high disulfiram dose lost as much as 40% of their body weight in just four weeks, effectively normalizing their weight to that of obese mice who were switched back to standard diet. Mice in either disulfiram dose diet group became leaner and showed significant improvement in blood glucose levels on par with the mice who were returned to standard diet. 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.