(The FASEB Journal. 2008;22:958.3)
© 2008 FASEB
(The FASEB Journal. 2008;22:958.3.)
© 2008 FASEB
Contraction-induced fatty acid uptake and oxidation are regulated in part via CaMKKβ-dependent AMPK activation in perfused rat muscle
Marcia Jeanine Abbott1 and
Lorraine Turcotte2
1 Department of Biological Sciences
2 Department of Kinesiology, University of Southern California, Los Angeles, CA
ABSTRACT
Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) and AMP-activated protein kinase (AMPK) have been individually implicated in the regulation of muscle substrate metabolism during exercise. The purpose of this study was to determine if CaMKKβ is involved in the regulation of FA metabolism during muscle contraction in rats. Rat hindlimbs were perfused at rest (n=16), with 3mM caffeine (n=15), with 2mM AICAR (n=16), or during moderate intensity muscle contraction (n=14), and with or without 5µM STO-609, a CaMKKβ inhibitor. FA uptake and oxidation increased (P<0.05) by 83 and 68% with caffeine treatment, 54 and 94% with AICAR treatment and 78 and 126% with muscle contraction. STO-609 abolished (P<0.05) caffeine- and contraction-induced FA uptake and oxidation, but had no effect with AICAR treatment (P>0.05). CaMKKβ activity was increased (P<0.05) 102% by caffeine treatment and 136% by muscle contraction, but was not affected by AICAR treatment (P>0.05). STO-609 prevented the caffeine- and contraction-induced increase in CaMKKβ activity. Caffeine, AICAR and muscle contraction increased (P<0.05) AMPK
2 activity by 240%, 12-fold and 496%, but did not affect (P>0.05) AMPK1 activity. STO-609 decreased (P<0.05) AMPK2 activity by 54 and 52% during caffeine treatment and muscle contraction, but did not affect (P>0.05) AICAR-induced activity. These results show the critical importance of Ca2+-dependent signaling via CaMKKβ activation in the regulation of FA uptake and oxidation in contracting rat skeletal muscle.
