First the mice were given 48 hours to become accustomed to a metabolic chamber, which allows researchers to monitor energy intake and expenditure. Both groups showed identical carbohydrate use during the dark cycle (when they are most active) prior to treatment. Then, at the beginning of the light cycle, when the animals are least active, one group was injected with an experimental compound known as SU6656 that blocks Fyn kinase, while the control group received an inert substance.
After injection, the control mice reduced energy use as their bodies switched to normal lipid production. On the other hand, the treated animals continued to expend energy at a significantly higher rate than the controls, although there was no measurable difference in physical activity. Both groups experienced a slight reduction in lean mass, but the SU6656-treated mice had a significant reduction in fat mass. Overall, the treated mice had a 40 percent greater weight loss than the control group and a 14 percent increase in energy expenditure.
Obesity occurs “when there is an imbalance between what we eat and what we burn,” and the problem is not going away, said study lead Dr. Claire Bastie. “This is a new mechanism to help the body to burn extra energy.” Bastie cautions that more research is needed to find a compound that can block Fyn kinase safely in humans. Because the enzyme has effects in the brain as well as muscle and fat tissue, scientists would need to develop a drug that targets only the molecular players they want it to. “Our next goal is to design something extremely specific to muscle and adipose,” she said.
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