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Contraction‐induced fatty acid uptake and oxidation are regulated in part via CaMKKβ‐dependent AMPK activation in perfused rat muscle
Author(s) -
Abbott Marcia Jeanine,
Turcotte Lorraine
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.958.3
Subject(s) - ampk , endocrinology , chemistry , medicine , caffeine , contraction (grammar) , protein kinase a , muscle contraction , skeletal muscle , amp activated protein kinase , kinase , biochemistry , biology
Ca 2+ /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 α2 activity by 240%, 12‐fold and 496%, but did not affect ( P >0.05) AMPK α1 activity. STO‐609 decreased ( P <0.05) AMPK α2 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 Ca 2+ ‐dependent signaling via CaMKKβ activation in the regulation of FA uptake and oxidation in contracting rat skeletal muscle.