TY - JOUR
T1 - Sarcolemmal ATP-Sensitive K+ Channels Control Energy Expenditure Determining Body Weight
AU - Alekseev, Alexey E.
AU - Reyes, Santiago
AU - Yamada, Satsuki
AU - Hodgson-Zingman, Denice M.
AU - Sattiraju, Srinivasan
AU - Zhu, Zhiyong
AU - Sierra, Ana
AU - Gerbin, Marina
AU - Coetzee, William A.
AU - Goldhamer, David J.
AU - Terzic, Andre
AU - Zingman, Leonid V.
N1 - Funding Information:
The authors are particularly grateful to Dr. T. Miki (Chiba University) and Dr. S. Seino (Kobe University) for providing the Kir6.2-KO model. We further thank Drs. P. Mishra and S. Macura (Mayo Clinic Analytical NMR Facility) for expertise with NMR imaging, Drs. K. Campbell and J. Lueck (University of Iowa) for guidance with myofiber isolation, L. Rowe (Mayo Clinic) for assistance with histological specimens, E. Stepniak (University of Iowa) for technical assistance, and Dr. S.I. Loginov (Surgut University) for valuable discussion. This work was supported by the Gerstner Family Career Development Award in Individualized Medicine (A.E.A.); Mayo Graduate School Fellowship (S.R.); American Society for Clinical Pharmacology and Therapeutics Young Investigator Award (S.Y.); NIH T32GM008685 (S.S.); NIH RO1HL64822 (A.T.); NIH AR052777 (D.J.G.); Marriott Heart Diseases Research Program, Marriott Foundation (A.T.); and in part by the Medical Research Initiative Roy J. Carver Charitable Trust pilot grant and Fraternal Order of Eagles, Iowa Aerie grant (L.V.Z. and D.M.H.-Z.).
PY - 2010/1/6
Y1 - 2010/1/6
N2 - Metabolic processes that regulate muscle energy use are major determinants of bodily energy balance. Here, we find that sarcolemmal ATP-sensitive K+ (KATP) channels, which couple membrane excitability with cellular metabolic pathways, set muscle energy expenditure under physiological stimuli. Disruption of KATP 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 KATP channel-deficient striated muscles reduced glycogen and fat body depots, promoting a lean phenotype. The propensity to lesser body weight imposed by KATP channel deficit persisted under a high-fat diet, yet obesity restriction was achieved at the cost of compromised physical endurance. Thus, sarcolemmal KATP 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.
AB - Metabolic processes that regulate muscle energy use are major determinants of bodily energy balance. Here, we find that sarcolemmal ATP-sensitive K+ (KATP) channels, which couple membrane excitability with cellular metabolic pathways, set muscle energy expenditure under physiological stimuli. Disruption of KATP 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 KATP channel-deficient striated muscles reduced glycogen and fat body depots, promoting a lean phenotype. The propensity to lesser body weight imposed by KATP channel deficit persisted under a high-fat diet, yet obesity restriction was achieved at the cost of compromised physical endurance. Thus, sarcolemmal KATP 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.
KW - HUMDISEASE
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U2 - 10.1016/j.cmet.2009.11.009
DO - 10.1016/j.cmet.2009.11.009
M3 - Article
C2 - 20074528
AN - SCOPUS:73049095036
SN - 1550-4131
VL - 11
SP - 58
EP - 69
JO - Cell Metabolism
JF - Cell Metabolism
IS - 1
ER -