Jan. 6, 2010
Study provides insight into pathway linked to obesity
A new study involving the University of Iowa, Mayo Clinic and two other institutions provides insight on weight control, suggesting that a ATP-sensitive potassium channel critical to survival and stress adaptation can contribute to fat deposition and obesity.
The investigation reveals how the ATP-sensitive potassium channel in the heart and skeletal muscles affects the balance between food intake and energy used. The study, which was done in animal models, appears in the January issue of the journal Cell Metabolism.
The collaborative study involved lead author Alexey Alekseev, Ph.D., assistant professor at Mayo Clinic, as well as scientists from the University of Connecticut and New York University School of Medicine.
The findings point to a potential pathway through which to manage and prevent obesity, said Leonid Zingman, M.D., senior study author and UI assistant professor of internal medicine, who began the research while at Mayo Clinic in the laboratory of Andre Terzic, M.D.
"We were interested in better understanding how energy balance is regulated, and so we focused on the ATP-sensitive potassium channel in muscles," Zingman said. "This 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.
"Our work indicates that the channel limits how certain muscle cells, called myocytes, use energy under normal workload conditions," Zingman added.
When researchers disrupted the channel's function in muscles of mice, 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 to obesity was achieved at the cost of reduced endurance.
"Indeed, disrupting the channel made the mice burn more calories even while at rest and also made them less fuel-efficient when exercising, and therefore less capable of maintaining physical performance," Zingman said. "Through evolution, living organisms have become energy-saving. They responded to limited food resources and the high energy needed to survive by becoming energy efficient.
"But now, with excess food supply and an inactive lifestyle, this energy efficiency is a problem for humans," Zingman added.
The researchers are interested in whether it is possible to interfere with this "biological perfection" to manage obesity without negatively affecting heart and muscle function.
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.
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