A brand-new kind of drug, tested in mice, shows promising new results that could lead to the development of a new weight-loss drug that mimics exercise.
The new compound, developed and tested
by a University of Florida professor of pharmacy and his colleagues, leads
obese mice to lose weight by convincing the body’s muscles that they are
exercising more than they really are, boosting the animals’ metabolism.
It also increases endurance, helping
mice run nearly 50% further than they could before. All without the mice
lifting 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 like
obesity, diabetes, and age-related muscle loss. The research comes as drugs
like Ozempic have provided a breakthrough in reducing appetite, helping treat
these metabolic diseases.
But the new drug, known as SLU-PP-332,
doesn’t affect appetite or food intake. Nor does it cause mice to exercise
more. Instead, the drug boosts a natural metabolic pathway that typically
responds to exercise. In effect, the drug makes the body act like it is
training for a marathon, 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.”
With a team of researchers at Washington
University in St. Louis and St. Louis University, Burris published his findings Sept. 22 in the Journal of Pharmacology and Experimental
Therapeutics.
The new drug targets a group of proteins
in the body known as ERRs, which are responsible for activating some of the
most important metabolic pathways in energy-gobbling tissues like muscles, the
heart, and the brain. The ERRs are more active when people exercise, but they
have proven difficult to activate with drugs.
In another paper published in March, the researchers reported that they had successfully
designed SLU-PP-332 to boost activity of the ERRs. They also observed that the
compound allowed normal-weight mice to run for 70% longer and 45% further than
mice not receiving 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% of their
body weight. Yet the mice kept eating the same amount of food and didn’t exercise
any more.
“They use more energy just living,”
Burris said.
So far, the drug hasn’t generated any
severe side effects. The next step in developing SLU-PP-332 into a drug
candidate will be to refine its structure, ideally making it available as a pill
instead of an injection. Then the drug would be tested for side effects in more
animal models before making the jump to human trials.
Other exercise mimetics have been
tested, but none have made it to market, in part because it takes years to
develop a new drug. Targeting obesity, specifically, with a drug has
historically been difficult because of how complex obesity is. That was until
Ozempic, Wegovy, and Mounjaro, developed to treat diabetes, also caused people
to lose weight. This development led to a surge of interest, research, and
funding for drugs that could treat these metabolic diseases through different
biological pathways.
Burris says the greatest hope for the
new drug might be in 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 it will take more research to understand the
drug’s full potential.
“This may be able to keep people
healthier as they age,” Burris said.
Source: https://news.ufl.edu/2023/09/exercise-mimicking-drug/
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