Specific drug class can reverse diet-induced obesity, fatty liver and diabetes in mice

Researchers at the Karolinska Institute may have found a new way to treat obesity and related disorders by targeting the cells’ powerhouses, the mitochondria. A study published in Metabolism of Nature shows that a specific class of drugs that block mitochondrial function can reverse diet-induced obesity, fatty liver and diabetes in mice.

Mitochondria are essential to human health as they process the nutrients in the food we eat and gather the energy needed for various processes in the cell. They are central regulators of metabolism, which is very dynamic and can be reprogrammed and reprogrammed according to different needs or in response to disease.

Increased fat metabolism

Professor Nils-Göran Larsson’s research group at the Karolinska Institute in Sweden recently developed highly specific drug candidates that block mitochondrial function, and thus cellular energy production, for the treatment of cancer. Now researchers have shown that these drugs also have a beneficial effect on metabolism in mice.

Four weeks of treatment resulted in an unexpected increase in fat metabolism, resulting in dramatic weight loss, reduction in liver fat accumulation, and restoration of glucose tolerance.”

Taolin Yuan, Postdoctoral Researcher at Department of Medical Biochemistry and Biophysics, Karolinska Institutet

The treatment was administered orally to male obese mice fed a high-fat diet. The surprising result suggests that blocking the cells’ energy production may reverse obesity and diabetes.

Collaboration with biotech company

“It is exciting that we have identified a new potential strategy for the treatment of common diseases such as obesity and type 2 diabetes,” says Professor Nils-Göran Larsson. “We now aim to further investigate the mechanisms that may explain the drugs’ effect. We have also started a collaboration with a biotech company to see if this can be developed further into a treatment for humans. However, it will be many years before we know if it works,” he concludes.

The study was funded by the Novo Nordisk Foundation, the Swedish Diabetes Foundation, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, ALF funding, the Swedish Cancer Society and the Swedish Brain Foundation. Nils-Göran Larsson is a scientific founder and has shares in Pretzel Therapeutics Inc. Three of the co-authors are employees of the Lead Discovery Center and are listed as co-inventors on a patent application relating to mitochondrial RNA polymerase inhibitors for the treatment of cancer.