October 2, 2023: A drug that mimics the benefits of rigorous exercise has been developed on mice by scientists at the University of Florida.
The drug was found to increase muscle gain, boost metabolism and lose weight in mammals. It is part of a proposed class of treatments known as “exercise mimetics,” which imitate the physiological adaptations associated with physical activities.
The drug may be effective in the treatment of a range of diseases, including obesity and metabolic syndrome.
Metabolic syndrome is a condition that includes a cluster of risk factors specific to cardiovascular disease. The cluster of metabolic factors includes abdominal obesity, high blood pressure, impaired fasting glucose, high triglyceride levels, and low HDL cholesterol levels.
The molecule, called SLU-PP-332, was administered in diet-induced obese mice and the effects on a range of metabolic parameters were assessed.
The mimics induced benefits on whole-body metabolism in mice including increased energy expenditure and fatty acid oxidation. These effects were accompanied by decreased fat mass accumulation. The results were published their results in the Journal of Pharmacology and Experimental Therapeutics.
Additionally, the Estrogen Related Receptor (ERR) agonist effectively reduced obesity and improved insulin sensitivity in models of metabolic syndrome.
In obese mice SLU-PP-332 reduced fat mass and improved glucose tolerance, suggesting a potential use of ERR agonists in the treatment of a range of metabolic diseases including obesity and type 2 diabetes,” according to the study.
A majority of the exercise mimetic activity, such as increased skeletal muscle oxidative fibres, higher fatty acid oxidation and enhanced exercise endurance, was associated with targeting ERR in the skeletal muscle, additional target tissues such as the liver may also play a role.
Obesity is a major health issue and is a predisposing risk factor for early mortality due to multiple diseases including cancers, cardiovascular disease, and type 2 diabetes.
Obesity is associated with the accumulation of fat in the skeletal muscle which leads to reduced metabolic efficiency and insulin resistance.
“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 the University of Florida who led the recent research into the new drug.
Maintaining muscle mass
“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,” Prof Burris added. “And the animals start losing weight.”
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,” Prof Burris said.
The greatest hope for the new drug might be in maintaining muscle mass during weight loss – which often threatens lean muscle mass.
During ageing, when the body naturally responds less strongly to exercise, lean muscle becomes the casualty. It will take more research to understand the drug’s full potential, Prof Burris said. “This may be able to keep people healthier as they age.”