Sarcolemmal ATP-sensitive K(+) channels control energy expenditure determining body weight.
Metabolic processes that regulate muscle energy use are major determinants of bodily energy balance. Here, we find that sarcolemmal ATP-sensitive K(+) (K(ATP)) channels, which couple membrane excitability with cellular metabolic pathways, set muscle energy expenditure under physiological stimuli. Disruption of K(ATP) channel function provoked, under conditions of unaltered locomotor activity and blood substrate availability, an extra energy cost of cardiac and skeletal muscle performance. Inefficient fuel metabolism in K(ATP) channel-deficient striated muscles reduced glycogen and fat body depots, promoting a lean phenotype. The propensity to lesser body weight imposed by K(ATP) channel deficit persisted under a high-fat diet, yet obesity restriction was achieved at the cost of compromised physical endurance. Thus, sarcolemmal K(ATP) channels govern muscle energy economy, and their downregulation in a tissue-specific manner could present an antiobesity strategy by rendering muscle increasingly thermogenic at rest and less fuel efficient during exercise.
Alekseev
Alexey E
AE
Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA. alekseev.alexey@mayo.edu
Reyes
Santiago
S
Yamada
Satsuki
S
Hodgson-Zingman
Denice M
DM
Sattiraju
Srinivasan
S
Zhu
Zhiyong
Z
Sierra
Ana
A
Gerbin
Marina
M
Coetzee
William A
WA
Goldhamer
David J
DJ
Terzic
Andre
A
Zingman
Leonid V
LV
D000818:Animals; D001835:Body Weight; D004041:Dietary Fats; D004435:Eating; D004734:Energy Metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D024661:Potassium Channels, Inwardly Rectifying / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism*; D000099161:Kcnj11 Channel
D004041:Dietary Fats; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel