The new findings may provide the basis of a therapy that could help people to overcome the body's natural resistance to weight loss."This study shows for the first time that this energy efficiency can be manipulated in a clinically translatable way," said Denice Hodgson-Zingman from the University of Iowa and co-author of the study.

"While such an approach would not replace the need for a healthy diet or exercise, it could jump start the process of weight loss by overcoming the initial hurdles imposed by our energy-efficient physiology," Denice noted.

An earlier study found that a protein called ATP-sensitive potassium (KATP) channel is a powerful modulator of energy efficiency in skeletal muscle even during low-intensity activity. Now, the team has shown that altering the activity of the KATP protein causes skeletal muscles to become less efficient and burn more calories.

For the study, the team made a compound called a vivo-morpholino, which suppresses production of KATP. Injecting this compound into the thigh muscles of mice produced a local loss of the protein but did not affect the protein in other organs or even in neighbouring skeletal muscles.

The injected muscles burned more calories than untreated muscle without significantly affecting the muscle's ability to tolerate exercise."By making skeletal muscles less energy efficient, they burn more calories, even while doing normal daily activities," said Leonid Zingman from the University of Iowa and co-author.

"With this intervention, the benefits of exercise in burning calories could be accessible to a broader range of people by making the calorie burning effects of skeletal muscle greater even at low levels of activity that most people would be able to undertake," Zingman said.

The study appeared in the journal Molecular Therapy.


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