UI study provides insight into pathway linked to obesity

Findings by University of Iowa researchers who collaborated with the Mayo Clinic and other institutions could lead to medical treatments for obesity.

The new study, reported in the journal Cell Metabolism, revealed how a channel in the heart and skeletal muscles affects the balance between food intake and energy used.

Investigators found that disrupting the ATP-sensitive potassium channel made mice burn more calories even while at rest, but also made them less fuel efficient when exercising.

ATP, or adenosine triphosphate, is the “energy currency” used by cells in the body.

The findings point to a potential pathway through which to manage and prevent obesity, said Dr. Leonid Zingman, senior study author and UI assistant professor of internal medicine, who began the research while at the Mayo Clinic.

“The ion channel, which is present in many tissues, had been studied extensively, but its role in heart and skeletal muscle function under normal, not stressed, conditions has not been previously understood,” Zingman said. “Our work indicates that the channel limits how certain muscle cells, called myocytes, use energy under normal workload conditions.”

When researchers disrupted the channel's function in muscles, the mice used more energy and became lean even while on a high-fat diet. In essence, the mice became resistant to obesity.

However, this resistance was met at the cost of reduced endurance.

“Through evolution, living organisms have become energy-saving. They responded to limited food resources and the high energy need to survive by becoming energy efficient,” Zingman said. “But now, with excess food supply and an inactive lifestyle, this energy efficiency is a problem for humans.”

Researchers are interested in whether interfering with this “biological perfection” is possible to manage obesity without negatively affecting heart and muscle function.

“While mechanisms that preserve energy are naturally protective - in times of food shortage or environmental stress - they promote obesity in a sedentary, modern society,” said lead author Alexey Alekseev of the Mayo Clinic.

Alekseev said findings suggest that targeting the channel function, specifically in muscle, could offer a new option for obese patients with lower capacity for exercise.

Besides the UI and Mayo, the study included scientists from the University of Connecticut and New York University School of Medicine.

The study was supported by Gerstner Family Career Development Award in Industrialized Medicine, Mayo Graduate School Fellowship, National Institutes of Health grants, Marriot Disease Research Program/Marriot Foundation, and by a Medical Research Initiative Roy J. Carver Charitable Trust pilot grant and a Fraternal Order of Eagles, Iowa Aerie, grant.