Mayo researchers collaborating with investigators at the University of Iowa,
University of Connecticut and New York University (NYU) have discovered a
molecular mechanism that controls energy expenditure in muscles and helps
determine body weight. Researchers say this could lead to a new medical approach
in treating obesity. The findings appear in the journal Cell Metabolism.
The energy-saving mechanism is controlled by ATP-sensitive potassium (KATP)
channels. ATP, or adenosine triphosphate, is the "energy currency" utilized by
cells in the body. These particular channels can sense ATP pools and regulate
heart and skeletal muscle performance accordingly. Animals lacking this
energy-saving mechanism burn more stored energy by dissipating more heat when at
rest or when normally active.
As in humans, excess energy from food is stored as glycogen or fat that could be
converted into ATP according to energy demand. Eliminating the KATP channel
forces the body to use energy less efficiently, consuming more and storing less
gaining low weight, even when on a high-calorie "Western" diet.
"While mechanisms that preserve energy are naturally protective — in times of
food shortage or environmental stress — they promote obesity in a sedentary,
modern society," says Alexey Alekseev, Ph.D., Mayo Clinic electrophysiologist
and first author of the study. "Our findings suggest that therapeutic targeting
of the KATP channel function, specifically in muscle, could offer a new option
for obese patients with lower capacity for exercise."
How the study was done
Dr. Alekseev and his colleagues suspected that the KATP channel could control
energy expenditure. To test the hypothesis, they studied genetically modified
mice in which the KATP channel had been inactivated in the whole body or muscle
tissues. They compared these mice to normal mice and found that as early as 5
months of age, the modified mice were leaner and stayed that way throughout
their life span.
Researchers compared activity patterns, hormone levels, food intake, and
respiratory gas exchange while at rest and under moderate exercise. A hallmark
of the study was the discovery that activity in the absence of the KATP channel
function resulted in increased consumption of carbohydrates and lipids. That, in
turn, led to enforced burning of glycogen and stored body fat.
"By sensing cellular energy content, KATP channels continuously, at any activity
level, optimize energy use and define the balance between energy availability
and consumption," explains Dr. Alekseev. "In principle, a positive energy
balance favoring weight gain could be reversed by targeting muscle KATP channels
to control obesity in patients with low to moderate exercise capacity imposed by
the overweight state."
