title: Caffeine-stimulated fatty acid oxidation is blunted in CD36 null mice.
abstract: OBJECTIVE
  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 (3 mm) 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 carboxylase comparably in WT and CD36-KO.
  
  
  CONCLUSIONS
  These studies indicate that sarcolemmal CD36-mediated fatty acid transport is a primary mediator of the calcium-induced increase in muscle fatty acid oxidation.
authors.affiliation: Department of Human Health and Nutritional Science, University of Guelph, Guelph, ON, Canada.
authors.forename: J S V
authors.initials: JSV
authors.lastname: Lally
authors.affiliation: Department of Human Health and Nutritional Science, University of Guelph, Guelph, ON, Canada.
authors.forename: S S
authors.initials: SS
authors.lastname: Jain
authors.affiliation: Department of Human Health and Nutritional Science, University of Guelph, Guelph, ON, Canada.
authors.forename: X X
authors.initials: XX
authors.lastname: Han
authors.affiliation: Department of Human Health and Nutritional Science, University of Guelph, Guelph, ON, Canada.
authors.forename: L A
authors.initials: LA
authors.lastname: Snook
authors.affiliation: Department of Molecular Genetics, Maastricht University, Maastricht, the Netherlands.
authors.forename: J F C
authors.initials: JFC
authors.lastname: Glatz
authors.affiliation: Department of Molecular Genetics, Maastricht University, Maastricht, the Netherlands.
authors.forename: J J F P
authors.initials: JJFP
authors.lastname: Luiken
authors.affiliation: Department of Human Health and Nutritional Science, University of Guelph, Guelph, ON, Canada.
authors.forename: J
authors.initials: J
authors.lastname: McFarlan
authors.affiliation: Department of Human Health and Nutritional Science, University of Guelph, Guelph, ON, Canada.
authors.forename: G P
authors.initials: GP
authors.lastname: Holloway
authors.affiliation: Department of Human Health and Nutritional Science, University of Guelph, Guelph, ON, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Bonen
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D019308:Palmitic Acid / Q000378:metabolism*
chemical_list: D018955:CD36 Antigens; D019308:Palmitic Acid; D002110:Caffeine; D002118:Calcium