How many times have you dreamed of a ‘miracle pill’ that mimics the effects of exercise? This dream could come true thanks to the work carried out by researchers at the University of Florida, (USA), who have just tested a drug on mice that mimics the effects of sport, helping to lose weight and increasing muscle activity.
The new compound has made obese mice lose weight by convincing the body’s muscles that they are exercising more than they really do, stimulating the animals’ metabolism. In addition, it has managed to increase their resistance, helping the mice to run almost 50 percent more than before. All without the mice moving a paw.
The drug belongs to a class known as “exercise mimetics,” which provide some of the benefits of exercise without increasing physical activity. The new treatment is in the early stages of development, but could one day be tested in people to treat diseases such as obesity, diabetes and age-related muscle loss.
This research occurs in the midst of a revolution in drugs that attack obesity, compounds such as ‘Ozempic’ — which helps the body reduce blood sugar levels and lose weight — that have provided a breakthrough in reducing appetite, helping to treat these metabolic diseases.
The new investigational drug, known as SLU-PP-332, does not affect appetite or food intake as semaglutide does. Likewise, it does not make the mice exercise more. Instead, the drug stimulates a natural metabolic pathway that normally responds to exercise. Actually, what this new compound does is that the body acts as if it were training for a marathon, which causes greater energy expenditure and faster metabolism of fat in the body.
“This compound basically tells skeletal muscle to make the same changes that are seen during resistance training,” says Thomas Burris, a professor of pharmacy at UF who led the recent research on the new drug.
“When you treat mice with the drug, you can see that their entire body’s metabolism turns to using fatty acids, which is very similar to what people use when they fast or exercise. And the animals start to lose weight “says the expert.
The research has been carried out by a team of researchers from Washington University in St. Louis and St. Louis University; and the preliminary results have just been published in the ‘Journal of Pharmacology and Experimental Therapeutics’.
The new drug targets a group of proteins in the body known as ERR, which are responsible for activating some of the most important metabolic pathways in energy-consuming tissues, such as muscles, heart and brain. ERRs are most active when people exercise, but it has proven difficult to activate them with medications.
In a previous paper, published in March of this year, the researchers reported that they had successfully engineered SLU-PP-332 to boost ERR activity. They also observed that the compound allowed normal-weight mice to run 70 percent longer and 45 percent longer than mice that did not receive the drug.
In their latest research, the team tested the drug on obese mice. Treating obese mice twice a day for a month caused them to gain 10 times less fat than untreated mice and lose 12 percent of their body weight. However, the mice continued to eat the same amount of food and did not exercise any more. Thus, it was observed that “they use more energy simply by living,” said the leader of the study.
In other work the Burris lab is about to publish, researchers have seen evidence that the compound can also treat heart failure in mice by strengthening the heart muscle.
So far, the drug has not caused serious side effects. The next step in developing SLU-PP-332 as a drug candidate will be to refine its structure, ideally making it available in pill form rather than an injection. The drug would then be tested for side effects in more animal models before making the jump to human trials.
Other exercise mimetics have been tried, but none have come to market, in part because it takes years to develop a new drug. Treating obesity, specifically, with a drug has historically been difficult because of how complex obesity is.
In fact, it is now with drugs such as ‘Ozempic’, ‘Wegovy’ and ‘Mounjaro’, developed to treat diabetes, that their usefulness has been seen in obese people so that they can lose weight. This development has led to increased interest in research and funding for drugs that could treat these metabolic diseases through different biological pathways.
For his part, Dr. Burris believes the best hope for the new drug could be maintaining muscle mass during weight loss – which often threatens lean muscle mass – or during aging, when the body naturally responds less strongly. to exercise. But, he admits, “more research will be needed to understand the full potential of the drug,” although he is almost certain that this drug “can help keep people healthier as they age.”
