Inhibiting skeletal muscle enzyme could boost exercise performance, fat burning capacity

Most cells in the body prefer burning sugar as an energy source but can draw on other energy sources, including fats, as needed. Exercise leverages this type of function in cells. Experiments by Harvard Medical University (HMS), US, scientists have recently found that mice engineered to lack a certain enzyme showed significant increases in exercise endurance and fat-burning capacity as a result.

In the experiments, the scientists isolated mouse cells grown in a sugar-rich and low-sugar environment. They observed how an enzyme known as prolyl hydroxylase 3 (PHD3) affected afatty acid-controlling enzyme (ACC2) and yet another enzyme called AMPK, which cancels out the chemical modifications to ACC2 in heart and skeletal muscle and enables fatty acids to enter the cell to be used as an energy source.

The scientists also wanted to know how things would play out if they removed the PHD3 enzyme and so engineered mice that do not express PHD3. These mice were put through a range of endurance exercise experiments.

“If we knock out PHD3,would that increase fat burning capacity and energy production and have a beneficial effect in skeletal muscle, which relies on energy for muscle function and exercise capacity?” questionedHMS professor of cell biology Marcia Haigis.

Surprisingly, mice lacking the PHD3 enzyme were able to and run 50% farther on a treadmill and endure  40% longer compared to the control group. They also exhibited a higher maximum oxygen uptake, an indicator of oxygen consumption rates and aerobic endurance. PHD3-deficient mice also had increased rates of fat metabolism and a different metabolic profile.

In another round of experiments, mice were engineered to lack the PHD3 enzyme only in skeletal muscle, where it is typically most highly expressed. The similar results produced indicate that inhibiting PHD3 in in skeletal muscle could be enough to boost exercise performance. Chiefly, a muscle-specific PHD3 knockout could help guide new applications in humans, such as novel strategies for treating muscle disorders, said Haigis.

Category: Features, Wellness and Complementary Therapies