Even though increasing caloric expenditure through eating less or exercising more (or both!) is still the number one way to lose some unwanted fat, prolonged dieting can sometimes force our bodies to go into starvation mode and erect a whole array of hormonal and physiological barriers to efficient energy use.
While this makes perfect sense in terms of evolutionary fitness, our increasingly sedentary lifestyle, coupled with largely unprecedented food availability, make this biochemical cleverness a big problem – it is estimated that around 30 per cent of American adults and anywhere between 10-30 per cent of Europeans are obese.
To help those struggling with weight loss, a group of scientists from the University of Iowa and the Iowa City VA Medical Centre has come up with a way to override this energy saving mechanism and allow muscles to burn more calories even with minimal changes in exercise habits.
“Our bodies are geared to be energetically efficient and this often works against us when we are trying to control or reduce our weight,” said study co-author Denice Hodgson-Zingman, MD, UI Associate Professor of Internal Medicine. “This study shows for the first time that this energy efficiency can be manipulated in a clinically translatable way. 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.”
The new paper, published in the journal Molecular Therapy, builds on previous research which demonstrated that a protein called ATP-sensitive potassium (KATP) is highly involved in regulating energy efficiency in skeletal muscle even during low-intensity activity.
Having shown that decreasing the concentration of KATP in muscles makes them more wasteful, the team went on to turn this discovery into an actual therapeutic intervention.
Since neither genetic manipulation used in earlier mouse studies, nor drugs that inhibit the protein channel – which could affect the heart and cause grave side effects – were a viable option, the researchers had to develop a compound that would target KATP locally.
The result was a cell-penetrating vivo-morpholino (in molecular biology – a molecule used to modify gene expression) that successfully stopped the production of ATP-sensitive potassium in mouse thigh muscles without affecting organs or neighbouring muscle groups, allowing the subjects to burn more calories while remaining just as exercise-tolerant as controls.
According to the authors of the study, their findings may translate into therapies for those with limited opportunities for exercise due to stroke, lung disease, arthritis and other conditions that decrease one’s capacity for physical exertion.
“By making skeletal muscles less energy efficient, they burn more calories, even while doing [normal] daily activities,” said study co-author Leonid Zingman, MD, UI Associate Professor of Internal Medicine and a staff physician at the Iowa City VA Medical Centre. “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.”