1 solution to obesity: Muscles that act as an energy drain

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1 solution to obesity: Muscles that act as an energy drain

http://www.eurekalert.org/pub_releases/2010-01/cp-ost122809.php

Many people have traded in their gas-guzzling old " clunkers " for newer and more

efficient models or cut back on energy use at home by opting for Energy Star

appliances and compact fluorescent light bulbs. But, when it comes to our

muscles, a little less efficiency might be just what the doctor ordered,

suggests a report in the January Cell Metabolism, a Cell Press publication.

The researchers from the Mayo Clinic and the University of Iowa have new insight

into an important " fuel gauge " in muscle. They've also uncovered evidence in

mice that treatments designed to disrupt those so-called sarcolemmal

ATP-sensitive K+ (KATP) channels specifically in muscles might allow us to

control our weight by increasing the number of calories our muscles will burn

with regular activity or exercise.

" The channels sense even minor changes in nucleotide energy and respond by

shortening the duration of action potentials and limiting energy-demanding

muscle contractility and maintenance of ion composition, " said ey Alekseev

of the Mayo Clinic. " If you don't have the channel, you will consume more

energy. The system normally has an energy-saving role, but with a sedentary

lifestyle and excess of food, it favors obesity. "

" In some ways it may seem paradoxical to fight against what is a very good

system for fueling our muscles with energy efficiency, " added Leonid Zingman of

the University of Iowa. " On the other hand, it's also paradoxical that many of

us today have an excessive food supply and we don't need to move. "

Earlier work had shown that the KATP channels found at the surface of heart and

skeletal muscle cells play a role under severely stressful conditions such as

heart disease, acting as a kind of safety valve. But their everyday role

remained unclear. After all, Alekseev said, ischemic heart disease really is a

modern human problem, not one experienced by organisms living in their natural

environments.

Now, they show that the KATP channels are responsible for keeping those muscle

and heart cells pumping without expending any more energy than they have to.

Animals with skeletal muscles that are deficient for the KATP channels store

less glucose in the form of glycogen and less fat to become leaner. The animals'

weight loss persists even when they eat diets that are high in fat. That

reduction in stored muscle energy comes with a price of reduced physical

endurance, however.

The researchers conclude that " sarcolemmal KATP channels govern muscle energy

economy, and their downregulation in a tissue-specific manner could present an

anti-obesity strategy by rendering muscle increasingly thermogenic at rest and

less fuel efficient during exercise. "

The findings also point Zingman to another general principle when it comes to

our weight.

" For me, the most surprising thing was how small changes can translate to

significant changes with time, " he said, noting that mice with and without the

channels start out the same in terms of body weight but start to diverge from

one another by the time they reach four months in age. " Limiting energy

consumption by a small fraction with every movement or beat of the heart can add

up to a significant change in total energy consumption. Small actions may really

make a huge difference. "

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The researchers include ey E. Alekseev, Mayo Clinic, Rochester, MN; Santiago

Reyes, Mayo Clinic, Rochester, MN; Satsuki Yamada, Mayo Clinic, Rochester, MN;

Denice M. Hodgson-Zingman, Mayo Clinic, Rochester, MN, University of Iowa, Iowa

City, IA; Srinivasan Sattiraju, Mayo Clinic, Rochester, MN; Zhiyong Zhu,

University of Iowa, Iowa City, IA; Ana Sierra, University of Iowa, Iowa City,

IA; Marina Gerbin, Mayo Clinic, Rochester, MN; A. Coetzee, New York

University School of Medicine, New York, NY; J. Goldhamer, University of

Connecticut, Storrs, CT; Andre Terzic, Mayo Clinic, Rochester, MN; and Leonid V.

Zingman, Mayo Clinic, Rochester, MN, University of Iowa, Iowa City, IA.