Fatty Acid Transfer Across the Myocardial Capillary Wall: No Evidence of a Substantial Role for Cytoplasmic Fatty Acid-binding Protein

Nieuwenhoven, Frans A. van; Verstijnen, C.; Eys, Guillaume J.J.M. van; Breda, Eric van; Jong, Y. F. De; Vusse, Ger J.; Glatz, Jan F. C.

doi:10.1006/jmcc.1994.1183

Cited by 25 publications

(10 citation statements)

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“…Cytoplasmic H-FABP Determinations-The contents of heart-type cytoplasmic FABP (H-FABPc) in homogenates and giant vesicles from heart and skeletal muscles were determined by a sandwich-type enzyme-linked immunosorbent assay as previously described (35,36). Because of the unavailability of the appropriate antibody we were not able to determine the adipocyte lipid binding protein (A-LBP), the predominant FABPc in adipose tissue.…”

Section: Methodsmentioning

confidence: 99%

Increased Rates of Fatty Acid Uptake and Plasmalemmal Fatty Acid Transporters in Obese Zucker Rats

Luiken¹,

Arumugam²,

Dyck³

et al. 2001

Journal of Biological Chemistry

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Giant vesicles were used to study the rates of uptake of long-chain fatty acids by heart, skeletal muscle, and adipose tissue of obese and lean Zucker rats. With obesity there was an increase in vesicular fatty acid uptake of 1.8-fold in heart, muscle and adipose tissue. In some tissues only fatty acid translocase (FAT) mRNA (heart, ؉37%; adipose, ؉80%) and fatty acid-binding protein (FABPpm) mRNA (heart, ؉148%; adipose, ؉196%) were increased. At the protein level FABPpm expression was not changed in any tissues except muscle (؉14%), and FAT/CD36 protein content was altered slightly in adipose tissue (؉26%). In marked contrast, the plasma membrane FAT/CD36 protein was increased in heart (؉60%), muscle (؉80%), and adipose tissue (؉50%). The plasma membrane FABPpm was altered only in heart (؉50%) and adipose tissues (؉70%). Thus, in obesity, alterations in fatty acid transport in metabolically important tissues are not associated with changes in fatty acid transporter mRNAs or altered fatty acid transport protein expression but with their increased abundance at the plasma membrane. We speculate that in obesity fatty acid transporters are relocated from an intracellular pool to the plasma membrane in heart, muscle, and adipose tissues.Fatty acids (FA) 1 are important substrates for most mammalian tissues. Based on their hydrophobic structure it has been postulated that FA are sequestered by cells through passive diffusion across the plasma membrane (cf. Ref. 1). However, other evidence has shown that FA also traverse the plasma membrane via a protein-mediated mechanism (cf. Refs. 2 and 3). Indeed, this latter system is quantitatively more important than passive diffusion, as FA uptake can be reduced markedly by inhibitors of protein-mediated membrane transport (4 -6) and by a reactive ester of oleate (4). Thus, a number of groups began to search for FA transport proteins.Several putative fatty acid transport proteins have been identified that promote the cellular uptake of FA. These are a 43-kDa plasma membrane fatty acid-binding protein (FABPpm) (7), identical to mitochondrial aspartate aminotransferase (7-9), and an 88-kDa heavily glycosylated fatty acid translocase (FAT/CD36), the rat homologue of human CD36 (10). In addition, to these membrane-associated proteins, a soluble cytoplasmic fatty acid-binding protein (FABPc) is also important for cellular FA uptake, because in FABPc null mice there is a marked decrease of FA influx into cardiac myocytes (11). FATP1, another putative fatty acid transport protein (12, 13), correlates inversely with fatty acid transport in muscle and heart (4), and this protein appears to be a very long-chain acyl-CoA synthetase (14, 15). These observations suggest that FATP1 is unlikely to be involved directly in fatty acid translocation across the plasma membrane.To examine the regulation of transmembrane fatty acid transport, we have characterized giant vesicles (4, 16, 17), which can be prepared from metabolically important tissue such as heart (4) and skeletal muscle (16, 17) as...

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Section: Methodsmentioning

confidence: 99%

Increased Rates of Fatty Acid Uptake and Plasmalemmal Fatty Acid Transporters in Obese Zucker Rats

Luiken¹,

Arumugam²,

Dyck³

et al. 2001

Journal of Biological Chemistry

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246

270

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“…A rabbit polyclonal antiserum against rat hepatic membrane FABP was a gift from Dr. Jorge Calles-Escandon (Glaxo SmithKline, Miami, FL). Generation of a polyclonal antiserum against recombinant rat L-FABP has been described previously (17).…”

Section: Animalsmentioning

confidence: 99%

Long‐chain fatty acid uptake by skeletal muscle is impaired in homozygous, but not heterozygous, heart‐type‐FABP null mice

Luiken

Koonen

Coumans

et al. 2003

Lipids

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Previous studies with cardiac myocytes from homozygous heart-type fatty acid (FA)-binding protein (H-FABP) -/- mice have indicated that this intracellular receptor protein for long-chain FA is involved in the cellular uptake of these substrates. Based on the knowledge that muscle FA uptake is a process highly sensitive to regulation by hormonal and mechanical stimuli, we studied whether H-FABP would play a role in this regulation. A suitable model system to answer this question is provided by H-FABP +/- mice, because in hindlimb muscles the content of H-FABP was measured to be 34% compared to wild-type mice. In these H-FABP +/- skeletal muscles, just as in H-FABP -/- muscles, contents of FA transporters, i.e., 43-kDa FABPpm and 88-kDa FAT/CD36, were similar compared to wild-type muscles, excluding possible compensatory mechanisms at the sarcolemmal level. Palmitate uptake rates were measured in giant vesicles prepared from hindlimb muscles of H-FABP -/-, H-FABP +/-, and H-FABP +/+ mice. For comparison, giant vesicles were isolated from liver, the tissue of which expresses a distinct type of FABP (i.e., L-FABP). Whereas in H-FABP -/- skeletal muscle FA uptake was reduced by 42-45%, FA uptake by H-FABP +/- skeletal muscle was not different from that in wild-type mice. In contrast, in liver from H-FABP -/- and from H-FABP +/- mice, FA uptake was not altered compared to wild-type animals, indicating that changes in FA uptake are restricted to H-FABP expressing tissues. It is concluded that H-FABP plays an important, yet merely permissive, role in FA uptake into muscle tissues.

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“…e ., the sarcolemma, ranges from 1.2 to 3.0 cm s -1 , which agrees quite well with the value of 1.61 cm s -1 , as determined by Kamp and Hamilton [ 17 ]. Permeability of the endothelial membranes was calculated to be appreciably lower than that of the sarcolemma, due to the low concentration of FABP in the endothelial cells as reported by van Nieuwenhoven and coworkers [ 30 ]. Furthermore, the permeability of the aqueous compartments ( P aqu ) is notably higher than that of the corresponding boundary zones ( P b ), indicating that diffusion of CpFa is not substantially hindered in the bulk region of the compartments.…”

Section: Discussionmentioning

confidence: 85%

“…Therefore, we used the corresponding value of Alb for FABP . For the endothelium, the concentration of FABP is not well known, but is reported not to exceed 4% of the FABP concentration in the cardiomyocyte [ 30 ]. In our first simulation ( Fig 4A ), the unknown concentration [ Cp ] ec has been adjusted for a best fit between model and measurement of the time course [ Fa L tot ] out ( t ).…”

Section: Resultsmentioning

confidence: 99%

“…Quantitative data on endothelial diffusion properties are relatively inaccurate because its Cp concentration cannot be easily measured in such a small compartment. Experimental data suggest that FABP fulfill the role of endothelial Cp , the concentration of which being probably on the order of 7 μmol l -1 [ 30 ], a value substantially lower than the FABP concentration in cardiomyocytes. It should be noted, however, that even this very low concentration of FABP in the endothelial cell is sufficiently high to permit Fa transfer though the endothelial cytoplasm at a physiologically relevant level.…”

Section: Discussionmentioning

confidence: 99%

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Modeling Fatty Acid Transfer from Artery to Cardiomyocyte

et al. 2015

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Despite the importance of oxidation of blood-borne long-chain fatty acids (Fa) in the cardiomyocytes for contractile energy of the heart, the mechanisms underlying the transfer of Fa from the coronary plasma to the cardiomyocyte is still incompletely understood. To obtain detailed insight into this transfer process, we designed a novel model of Fa transfer dynamics from coronary plasma through the endothelial cells and interstitium to the cardiomyocyte, applying standard physicochemical principles on diffusion and on the chemical equilibrium of Fa binding to carrier proteins Cp, like albumin in plasma and interstitium and Fatty Acid-Binding Proteins within endothelium and cardiomyocytes. Applying these principles, the present model strongly suggests that in the heart, binding and release of Fa to and from Cp in the aqueous border zones on both sides of the cell membranes form the major hindrance to Fa transfer. Although often considered, the membrane itself appears not to be a significant hindrance to diffusion of Fa. Proteins, residing in the cellular membrane, may facilitate transfer of Fa between Cp and membrane. The model is suited to simulate multiple tracer dilution experiments performed on isolated rabbit hearts administrating albumin and Fa as tracer substances into the coronary arterial perfusion line. Using parameter values on myocardial ultrastructure and physicochemical properties of Fa and Cp as reported in literature, simulated washout curves appear to be similar to the experimentally determined ones. We conclude therefore that the model is realistic and, hence, can be considered as a useful tool to better understand Fa transfer by evaluation of experimentally determined tracer washout curves.

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Fatty Acid Transfer Across the Myocardial Capillary Wall: No Evidence of a Substantial Role for Cytoplasmic Fatty Acid-binding Protein

Cited by 25 publications

References 0 publications

Increased Rates of Fatty Acid Uptake and Plasmalemmal Fatty Acid Transporters in Obese Zucker Rats

Increased Rates of Fatty Acid Uptake and Plasmalemmal Fatty Acid Transporters in Obese Zucker Rats

Long‐chain fatty acid uptake by skeletal muscle is impaired in homozygous, but not heterozygous, heart‐type‐FABP null mice

Modeling Fatty Acid Transfer from Artery to Cardiomyocyte

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