Capacity for Physical Endurance comes at a Price

Energy-conserving mechanisms that evolved as protective measures in an environment of restricted food supply and high demand for physical activity promote obesity in times of abundant food and low physical activity. ATP-sensitive potassium (K_ATP) channels in heart and skeletal muscle act as safety valves that limit action potentials to prevent energy depletion and are essential for survival and stress adaptation, but researchers at the Mayo Clinic, the University of Iowa, New York University School of Medicine and the University of Connecticut have now found that the channels also regulate cellular energy use under non-stressed physiological conditions and contribute to fat deposition and obesity.

Both when the animals were at rest or normally active, heart and skeletal muscles of mice lacking the K_ATP channel dissipated more energy as heat than those of wild type mice and the animals were resistant to increases in body weight caused by a Western-style high fat diet. However, since the animals’ muscles are also less efficient when exercising, they show lower endurance and are less capable of maintaining physical performance than wild type animals.

The authors hope that therapies that reduce the activity of K_ATP channels in a tissue-specific manner may have the potential to reduce obesity by making muscles more thermogenic at rest and less fuel efficient during exercise.

The study is published in the journal Cell Metabolism.