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Caffeine‐stimulated fatty acid oxidation is blunted in CD 36 null mice
Author(s) -
Lally J. S. V.,
Jain S. S.,
Han X. X.,
Snook L. A.,
Glatz J. F. C.,
Luiken J. J. F. P.,
McFarlan J.,
Holloway G. P.,
Bonen A.
Publication year - 2012
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2012.02396.x
Subject(s) - caffeine , beta oxidation , fatty acid , calcium , endocrinology , medicine , chemistry , sarcolemma , biochemistry , fatty acid metabolism , oxidative phosphorylation , cd36 , carnitine , skeletal muscle , biology , receptor
Aim: The increase in skeletal muscle fatty acid metabolism during exercise has been associated with the release of calcium. We examined whether this increase in fatty acid oxidation was attributable to a calcium‐induced translocation of the fatty acid transporter CD 36 to the sarcolemma, thereby providing an enhanced influx of fatty acids to increase their oxidation. Methods: Calcium release was triggered by caffeine (3 m m ) to examine fatty acid oxidation in intact soleus muscles of WT and CD 36‐ KO mice, while fatty acid transport and mitochondrial fatty acid oxidation were examined in giant vesicles and isolated mitochondria, respectively, from caffeine‐perfused hindlimb muscles of WT and CD 36‐ KO mice. Western blotting was used to examine calcium‐induced signalling. Results: In WT , caffeine stimulated muscle palmitate oxidation (+136%), but this was blunted in CD 36‐ KO mice (−70%). Dantrolene inhibited ( WT ) or abolished ( CD 36‐ KO ) caffeine‐induced palmitate oxidation. In muscle, caffeine‐stimulated palmitate oxidation was not attributable to altered mitochondrial palmitate oxidation. Instead, in WT , caffeine increased palmitate transport (+55%) and the translocation of fatty acid transporters CD 36, FABP pm, FATP 1 and FATP 4 (26–70%) to the sarcolemma. In CD 36‐ KO mice, caffeine‐stimulated FABP pm, and FATP 1 and 4 translocations were normal, but palmitate transport was blunted (−70%), comparable to the reductions in muscle palmitate oxidation. Caffeine did not alter the calcium‐/calmodulin‐dependent protein kinase II phosphorylation but did increase the phosphorylation of AMPK and acetyl‐ CoA carboxylase comparably in WT and CD 36‐ KO . Conclusion: These studies indicate that sarcolemmal CD 36‐mediated fatty acid transport is a primary mediator of the calcium‐induced increase in muscle fatty acid oxidation.