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. © 2010 Elsevier Inc. All rights reserved.
Alekseev, A. E., Reyes, S., Yamada, S., Hodgson-Zingman, D. M., Sattiraju, S., Zhu, Z., … Zingman, L. V. (2010). Sarcolemmal ATP-Sensitive K + Channels Control Energy Expenditure Determining Body Weight. Cell Metabolism, 11(1), 58–69. https://doi.org/10.1016/j.cmet.2009.11.009