The subcellular compartmentation of fatty acid transporters is regulated differently by insulin and by AICAR.
Cellular fatty acid uptake is facilitated by a number of fatty acid transporters, FAT/CD36, FABPpm and FATP1. It had been presumed that FABPpm, was confined to the plasma membrane and was not regulated. Here, we demonstrate for the first time that FABPpm and FATP1 are also present in intracellular depots in cardiac myocytes. While we confirmed previous work that insulin and AICAR each induced the translocation of FAT/CD36 from an intracellular depot to the PM, only AICAR, but not insulin, induced the translocation of FABPpm. Moreover, neither insulin nor AICAR induced the translocation of FATP1. Importantly, the increased plasmalemmal content of these LCFA transporters was associated with a concomitant increase in the initial rate of palmitate uptake into cardiac myocytes. Specifically, the insulin-stimulated increase in the rate of palmitate uptake (+60%) paralleled the insulin-stimulated increase in plasmalemmal FAT/CD36 (+34%). Similarly, the greater AICAR-stimulated increase in the rate of palmitate uptake (+90%) paralleled the AICAR-induced increase in both plasmalemmal proteins (FAT/CD36 (+40%)+FABPpm (+36%)). Inhibition of palmitate uptake with the specific FAT/CD36 inhibitor SSO indicated that FABPpm interacts with FAT/CD36 at the plasma membrane to facilitate the uptake of palmitate. In conclusion, (1) there appears to be tissue-specific sensitivity to insulin-induced FATP1 translocation, as it has been shown elsewhere that insulin induces FATP1 translocation in 3T3-L1 adipocytes, and (2) clearly, the subcellular distribution of FABPpm, as well as FAT/CD36, is acutely regulated in cardiac myocytes, although FABPpm and FAT/CD36 do not necessarily respond identically to the same stimuli.
Chabowski
Adrian
A
Department of Human Biology and Nutritional Sciences, University of Guelph, Ont., Canada.
Coort
Susan L M
SL
Calles-Escandon
Jorge
J
Tandon
Narendra N
NN
Glatz
Jan F C
JF
Luiken
Joost J F P
JJ
Bonen
Arend
A
D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D050612:Fatty Acid Transport Proteins; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D012265:Ribonucleotides / Q000494:pharmacology*
D018955:CD36 Antigens; D002352:Carrier Proteins; D050612:Fatty Acid Transport Proteins; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D007328:Insulin; D026901:Membrane Transport Proteins; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; C031143:AICA ribonucleotide