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09-26-2023

Exercise-mimicking drug tricks the body into burning fat  

A team of researchers led by the University of Florida has designed a new drug, currently undergoing trials in mice, which holds promise for evolving into a new medication aimed at promoting weight loss by simulating the effects of exercise. 

Elevates metabolism and endurance 

This drug, which was found to induce weight loss in obese mice, “tricks” the muscles into perceiving heightened levels of exercise, thereby elevating metabolism without the mice engaging in actual physical activity. 

Moreover, the compound elevates endurance levels, enabling mice to run almost 50 percent further than they could before, without significant physical exertion.

Exercise mimetics 

This groundbreaking medication falls under the category of “exercise mimetics,” which bestow some exercise benefits without necessitating an increase in physical activity. 

Although it is in the early stages of development, there is potential for its future application in humans for addressing conditions such as obesity, diabetes, and the decline of muscle mass associated with aging. 

Natural metabolic pathway 

This comes in the wake of drugs like Ozempic marking significant advancements in curbing appetite and managing metabolic diseases.

However, the distinguishing factor of the newly discovered SLU-PP-332 is that it neither influences appetite nor induces an increase in exercise, but rather enhances a natural metabolic pathway that typically responds to exercise. 

Heightened energy consumption

Essentially, the medication induces the body to behave as if it is undergoing intense training, resulting in heightened energy consumption and accelerated fat metabolism.

“This compound is basically telling skeletal muscle to make the same changes you see during endurance training,” explained senior author Thomas Burris, a professor of Pharmacy at the University of Florida. 

“When you treat mice with the drug, you can see that their whole body metabolism turns to using fatty acids, which is very similar to what people use when they are fasting or exercising. And the animals start losing weight.”

Targeting proteins 

SLU-PP-332 operates by targeting a set of proteins called ERRs, pivotal for triggering vital metabolic pathways in energy-consuming tissues such as muscles, heart, and brain. ERRs are notably more active during exercise, but activating them through medications has posed challenges.

In another paper published in March, scientists found that SLU-PP-332 can effectively amplify the activity of ERRs, and enable normal-weight mice to run 70 percent longer and 45 percent further compared to those not administered the drug.

Focus of the study 

In the current study, the focus was on testing the drug’s impact on obese mice. Administering the treatment twice daily for a month led to a tenfold reduction in fat accumulation and a 12 percent decrease in body weight in comparison to the control group, all while maintaining consistent food intake and activity levels. “They use more energy just living,” Burris noted.

Upcoming publications from the Burris lab indicate potential benefits of the compound in addressing heart failure in mice by fortifying the heart muscle.

To date, the compound hasn’t manifested any severe adverse effects. The subsequent phase in the development of SLU-PP-332 entails refining its structure, with the aim of formulating it as a pill as opposed to an injectable solution. Subsequently, extensive testing for side effects in diverse animal models will precede any human trials.

While various exercise mimetics have already undergone testing, market entry remains challenging, partly due to the length of the drug development process. 

Tackling obesity 

Moreover, tackling obesity through medication has historically been challenging due to how complex obesity’s causes and manifestations are. 

The breakthrough came with the advent of Ozempic, Wegovy, and Mounjaro, initially formulated for diabetes but also inducing weight loss, fueling interest and research in this domain.

These recent findings highlight the potential of this innovative drug in preserving muscle mass during weight loss periods or aging, when the body’s response to exercise diminishes. Nonetheless, further research is needed to uncover the full spectrum of the drug’s capabilities.

“This [drug] may be able to keep people healthier as they age,” Burris concluded.

The study is published in the Journal of Pharmacology and Experimental Therapeutics.

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