New research by a team of Australian scientists has unexpectedly revealed a novel anti-obesity drug. Initially working to create a drug that prevents insulin resistance, the researchers discovered in early animal tests that it instead prevented the animals from depositing and storing fat.
The long-term collaborative project involved scientists from the Centenary Institute and UNSW Sydney. The original plan was to find a way to inhibit insulin resistance, a key dysfunction that leads to a variety of metabolic diseases including type 2 diabetes.
Enzymes called ceramide synthases were the primary target. Increased levels of these compounds are specifically noted in the development of insulin resistance, and one enzyme in particular, ceramide synthase 1 (CerS1), was the main research target.
In the hopes of preventing insulin resistance the team developed a drug called P053, which was found to be highly specific in its ability to inhibit CerS1 activity. But when the drug was tested in mice the results were unexpected. It didn't prevent the onset of insulin resistance, but instead exerted an anti-obesity effect. The mice tested were fed a high-fat diet designed to bring on a variety of metabolic diseases and the drug ultimately increased the animal's ability to burn fat in skeletal muscles.
"We anticipated that targeting this enzyme would have insulin-sensitizing, rather than anti-obesity effects," explains Nigel Turner, one of the authors on the study. "However, since obesity is a strong risk factor for many different diseases including cardiovascular disease and cancer, any new therapy in this space could have widespread benefits."
It's hard to predict whether this research will eventually lead to a specific anti-obesity drug, as these early animal tests often prove fruitless when transferred to human clinical cases. The research in itself, though, is somewhat revelatory. This is the very first time scientists have effectively demonstrated a new drug that can so specifically target and inhibit an enzyme in the ceramide synthase family.
"From here, I would like to develop drugs which target both the ceramide synthase 1 and 6 enzymes together, and see whether it produces a much stronger anti-obesity and insulin sensitising response," says Anthony Don, from the Centenary Institute. "Although these drugs need more work before they are suitable for use in the clinic, our work so far has been a very important step in that direction."
The new research was published in the journal Nature Communications.
Source: University of New South Wales
