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Publication
AMPK controls exercise endurance, mitochondrial oxidative capacity, and skeletal
muscle integrity.
Authors Lantier L, Fentz J, Mounier R, Leclerc J, Treebak JT, Pehmøller C, Sanz N,
Sakakibara I, Saint-Amand E, Rimbaud S, Maire P, Marette A, Ventura-Clapier R,
Ferry A, Wojtaszewski JF, Foretz M, Viollet B
Submitted By Submitted Externally on 8/4/2017
Status Published
Journal FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Year 2014
Date Published
Volume : Pages 28 : 3211 - 24
PubMed Reference 24652947
Abstract AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that
plays a central role in skeletal muscle metabolism. We used skeletal
muscle-specific AMPKa1a2 double-knockout (mdKO) mice to provide direct genetic
evidence of the physiological importance of AMPK in regulating muscle exercise
capacity, mitochondrial function, and contraction-stimulated glucose uptake.
Exercise performance was significantly reduced in the mdKO mice, with a
reduction in maximal force production and fatigue resistance. An increase in the
proportion of myofibers with centralized nuclei was noted, as well as an
elevated expression of interleukin 6 (IL-6) mRNA, possibly consistent with mild
skeletal muscle injury. Notably, we found that AMPKa1 and AMPKa2 isoforms are
dispensable for contraction-induced skeletal muscle glucose transport, except
for male soleus muscle. However, the lack of skeletal muscle AMPK diminished
maximal ADP-stimulated mitochondrial respiration, showing an impairment at
complex I. This effect was not accompanied by changes in mitochondrial number,
indicating that AMPK regulates muscle metabolic adaptation through the
regulation of muscle mitochondrial oxidative capacity and mitochondrial
substrate utilization but not baseline mitochondrial muscle content. Together,
these results demonstrate that skeletal muscle AMPK has an unexpected role in
the regulation of mitochondrial oxidative phosphorylation that contributes to
the energy demands of the exercising muscle.-Lantier, L., Fentz, J., Mounier,
R., Leclerc, J., Treebak, J. T., Pehmøller, C., Sanz, N., Sakakibara, I.,
Saint-Amand, E., Rimbaud, S., Maire, P., Marette, A., Ventura-Clapier, R.,
Ferry, A., Wojtaszewski, J. F. P., Foretz, M., Viollet, B. AMPK controls
exercise endurance, mitochondrial oxidative capacity, and skeletal muscle
integrity.






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