AMPK-mediated increase in myocardial long-chain fatty acid uptake critically depends on sarcolemmal CD36.
CD36, also named fatty acid translocase, has been identified as a putative membrane transporter for long-chain fatty acids (LCFA). In the heart, contraction-induced 5' AMP-activated protein kinase (AMPK) signaling regulates cellular LCFA uptake through translocation of CD36 and possibly of other LCFA transporters from intracellular storage compartments to the sarcolemma. In this study, isolated cardiomyocytes from CD36(+/+)- and CD36(-/-) mice were used to investigate to what extent basal and AMPK-mediated LCFA uptake are CD36-dependent. Basal LCFA uptake was not altered in CD36(-/-) cardiomyocytes, most likely resulting from a (1.8-fold) compensatory upregulation of fatty acid-transport protein-1. The stimulatory effect of contraction-mimetic stimuli, oligomycin (2.5-fold) and dipyridamole (1.6-fold), on LCFA uptake into CD36(+/+) cardiomyocytes was almost completely lost in CD36(-/-) cardiomyocytes, despite that AMPK signaling was fully intact. CD36 is almost entirely responsible for AMPK-mediated stimulation of LCFA uptake in cardiomyocytes, indicating a pivotal role for CD36 in mediating changes in cardiac LCFA fluxes.
Habets
Daphna D J
DD
Department of Molecular Genetics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. d.habets@gen.unimaas.nl
Coumans
Will A
WA
Voshol
Peter J
PJ
den Boer
Marion A M
MA
Febbraio
Maria
M
Bonen
Arend
A
Glatz
Jan F C
JF
Luiken
Joost J F P
JJ
D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D018955:CD36 Antigens / Q000235:genetics* / Q000502:physiology*; D003847:Deoxyglucose / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D019308:Palmitic Acid / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism*
D018955:CD36 Antigens; D005230:Fatty Acids, Nonesterified; D009840:Oligomycins; D019308:Palmitic Acid; D003847:Deoxyglucose; D000263:Adenylate Kinase