The compound is reported to lead mice to lose weight by convincing the body’s muscles that they are exercising more than they are which boosts the animal’s metabolism. The researchers also report the drug increases endurance, helping the animals to run nearly 50% further than they previously could.
The new drug candidate belongs to the “exercise mimetics” class, which are designed to provide some of the benefits of exercise without increasing physical activity levels. While this new compound is still in the early stages, one day it could be tested on humans to treat obesity, diabetes, and age-related muscle loss.
Unlike the drug Ozempic which reduces appetite to treat certain metabolic diseases, compound SLU-PP-332 does not affect appetite or food intake, nor does it cause the mice to exercise more. This compound boosts a natural metabolic pathway that typically responds to exercise, making the body act like it is training, leading to increased energy expenditure and faster metabolism of fat in the body.
“This compound is basically telling skeletal muscle to make the same changes you see during endurance training,” said Thomas Burris, a professor of pharmacy at UF who led the recent research into the new drug. “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,” Burris added. “And the animals start losing weight.”
SLU-PP-332 targets ERRs proteins which are responsible for the activation of some of the metabolic pathways in the muscles, heart, and brain. ERRs are more active when exercising, but have proven difficult to activate with drugs. Previously the compound was observed to allow normal-weight mice to run 70% longer and 45% further than untreated animals. This research tested the compound on obesity, treating obese mice twice a day for a month, which was observed to cause 10 times less fat gain than untreated counterparts and a 12% loss of body weight with the mice eating the same amount of food and not doing any extra exercise.
“They use more energy just living,” Burris said.
The researchers report that thus far there have not been any severe side effects and are looking into refining its structure to make it available as a pill rather than an injection, before eventually moving on to more animal models to prepare for the jump to human trials. Other exercise mimetics have been tested but nine have made it to market for a variety of reasons.
In other research that is yet to be published, the researchers saw evidence of the compound being helpful in treating heart failure in mice by strengthening heart muscle. Another hope for this compound is in helping to maintain muscle mass during weight loss or during aging. However, additional research is required to understand the full potential of compound SLU-PP-332.
“This may be able to keep people healthier as they age,” Burris said.
