title: Overexpression of membrane-associated fatty acid binding protein (FABPpm) in vivo increases fatty acid sarcolemmal transport and metabolism.
abstract: Fatty acid translocase (FAT/CD36) is a key fatty acid transporter in skeletal muscle. However, the effects on fatty acid transport by another putative fatty acid transporter, plasma membrane-associated fatty acid binding protein (FABPpm), have not been determined in mammalian tissue. We examined the functional effects of overexpressing FABPpm on the rates of 1) palmitate transport across the sarcolemma and 2) palmitate metabolism in skeletal muscle. One muscle (soleus) was transfected with pTracer containing FABPpm cDNA. The contralateral muscle served as control. After injecting the FABPpm cDNA, muscles were electroporated. FABPpm overexpression was directly related to the quantity of DNA administered. Electrotransfection (200 microg/muscle) rapidly induced FABPpm protein overexpression (day 1, +92%, P < 0.05), which was further increased during the next few days (days 3-7; range +142% to +160%, P < 0.05). Sarcolemmal FABPpm was comparably increased (day 7, +173%, P < 0.05). Neither FAT/CD36 expression nor sarcolemmal FAT/CD36 content was altered. FABPpm overexpression increased the rates of palmitate transport (+79%, P < 0.05). Rates of palmitate incorporation into phospholipids were also increased +36%, as were the rates of palmitate oxidation (+20%). Rates of palmitate incorporation into triacylglycerol depots were not altered. These studies demonstrate that in mammalian tissue FABPpm overexpression increased the rates of palmitate transport across the sarcolemma, an effect that is independent of any changes in FAT/CD36. However, since the overexpression of plasmalemmal FABPpm (+173%) exceeded the effects on the rates of palmitate transport and metabolism, it appears that the overexpression of FABPpm alone is not sufficient to induce completely parallel increments in palmitate transport and metabolism. This suggests that other mechanisms are required to realize the full potential offered by FABPpm overexpression.
authors.affiliation: Department of Kinesiology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
authors.forename: David C
authors.initials: DC
authors.lastname: Clarke
authors.forename: Dragana
authors.initials: D
authors.lastname: Miskovic
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Han
authors.forename: Jorge
authors.initials: J
authors.lastname: Calles-Escandon
authors.forename: Jan F C
authors.initials: JF
authors.lastname: Glatz
authors.forename: Joost J F P
authors.initials: JJ
authors.lastname: Luiken
authors.forename: John J
authors.initials: JJ
authors.lastname: Heikkila
authors.forename: Arend
authors.initials: A
authors.lastname: Bonen
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018274:Electroporation / Q000379:methods; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D019308:Palmitic Acid / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D012508:Sarcolemma / Q000737:chemistry / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D019308:Palmitic Acid