Exercise-mimicking molecule may offer new treatments for obesity, type 2 diabetes

The new molecule - called "compound 14" - was developed by Ali Tavassoli, professor of chemical biology at the UK's University of Southampton, and his research team.

Compound 14 works by blocking the function of a cellular enzyme called ATIC, which plays an important role in metabolism.

Blocking ATIC function leads to accumulation of a molecule called ZMP in cells, which activates cells' central energy sensor - called AMPK - causing them to think they are low in energy. As such, the cells attempt to boost energy levels by increasing metabolism and uptake of glucose.

For their study, Tavassoli and colleagues tested compound 14 on two groups of mice. One group was fed a normal diet while the other was fed a high-fat diet, making them obese and glucose intolerant - a sign of prediabetes.

Their findings were recently published in the journal Chemistry & Biology.

The team found that mice treated with compound 14 who were fed a normal diet retained a normal weight and blood glucose levels.

However, mice fed a high-fat diet who were treated with a single dose of the compound demonstrated a reduction in blood glucose levels, bringing them to near-normal.

In addition, when the mice fed a high-fat diet were given a single dose of compound 14 daily for 7 days, their glucose tolerance improved and they shed approximately 5% of their body weight.

The team notes that compound 14 did not lead to weight loss in mice fed a normal diet.

Compound 14 'holds much promise' as a therapeutic agent

Based on their findings, the researchers say compound 14 could lead to effective treatments for obesity - a condition that affects more than a third of adults in the US.

What is more, they say the compound could open the door to better treatments for type 2 diabetes, which accounts for 90-95% of all diabetes cases in the US.

"Current treatments for type 2 diabetes center on elevating circulating insulin levels or improving the insulin sensitivity of an individual," says study co-author Dr. Felino Cagampang, associate professor in integrative physiology at the University of Southampton.

"The issue is that established drugs do not successfully enable patients with type 2 diabetes to achieve glycemic control and some can even result in weight gain, a leading factor driving the diabetes epidemic," he continues. "In contrast, this new molecule seems to reduce glucose levels and at the same time decrease body weight, but only if the subject is obese."

The team plans to further develop compound 14, monitor its long-term treatment outcome and determine exactly how it improves glucose intolerance and achieves weight loss.

If the compound is found to be safe and effective, the researchers have high hopes that it could be used to create new drugs for the treatment of obesity and diabetes. Tavassoli adds:

"There is a lot of evidence from previous studies that if you could selectively activate AMPK with a small molecule, it could have potential benefits in the treatment of several diseases, including type 2 diabetes, by acting as an exercise mimetic and increasing the uptake and usage of glucose and oxygen by cells.

Our molecule, which activates AMPK by altering cellular metabolism, therefore holds much promise as a potential therapeutic agent."

Last month, Medical News Today reported on a study suggesting the bacteria Staphylococcus aureus plays a role in the development of type 2 diabetes among people who are obese.

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