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Caffeine-Stimulated Fatty Acid Oxidation is Blunted In CD36-Null Mice.
MedLine Citation:
PMID:  22152018     Owner:  NLM     Status:  Publisher    
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 CD36 to the sarcolemma, thereby providing an enhanced influx of fatty acids to increase their oxidation. Methods:  Calcium release was triggered by caffeine (3mM) to examine fatty acid oxidation in intact soleus muscles of WT and CD36-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 CD36-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 CD36-KO mice (-70%). Dantrolene inhibited (WT) or abolished (CD36-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 CD36, FABPpm, FATP1 and FATP4 (26-70%) to the sarcolemma. In CD36-KO mice, caffeine-stimulated FABPpm, and FATP1 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 carboxlyase comparably in WT and CD36-KO. Conclusion:  These studies indicate that sarcolemmal CD36-mediated fatty acid transport is a primary mediator of the calcium-induced increase in muscle fatty acid oxidation.
James S V Lally; Swati S Jain; Xiao Xia Han; Laelie A Snook; Jan F C Glatz; Joost J F C Luiken; Jay McFarlan; Graham P Holloway; Arend Bonen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-8
Journal Detail:
Title:  Acta physiologica (Oxford, England)     Volume:  -     ISSN:  1748-1716     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101262545     Medline TA:  Acta Physiol (Oxf)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Scandinavian Physiological Society.
Department of Human Health and Nutritional Science, University of Guelph, Guelph, Ontario, Canada N1G 2W1 Department of Molecular Genetics, Maastricht University, 6200-MD Maastricht, The Netherlands.
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