Membrane transport of long-chain fatty acids: evidence for a facilitated process.

In mammalian cells, membrane uptake of long-chain fatty acids is mediated by two separate components; a passive component that is a linear function of the concentration of free fatty acid in the extracellular medium and a saturable component that exhibits the characteristics of a protein-facilitated process. This review summarizes the body of work that has accumulated related to the mechanism of fatty acid transport. Evidence in support of a facilitated uptake process is presented with relation to the different cell types or membrane systems where it was collected. The evidence includes saturation kinetics, competition between different substrates, and sensitivity to a variety of inhibitors. Recent knowledge related to membrane proteins thought to be implicated in the uptake process is reviewed. Factors that may modulate uptake or alter the relative contribution of passive versus facilitated components are briefly discussed. These include the molar ratio of fatty acid to its physiological carrier, plasma albumin and the metabolic or hormonal milieu.

[1]  B. Kiens,et al.  Palmitate transport and fatty acid transporters in red and white muscles. , 1998, American journal of physiology. Endocrinology and metabolism.

[2]  P. Watkins,et al.  Disruption of the Saccharomyces cerevisiae FAT1 Gene Decreases Very Long-chain Fatty Acyl-CoA Synthetase Activity and Elevates Intracellular Very Long-chain Fatty Acid Concentrations* , 1998, The Journal of Biological Chemistry.

[3]  J. Peters,et al.  Expression of Putative Fatty Acid Transporter Genes Are Regulated by Peroxisome Proliferator-activated Receptor α and γ Activators in a Tissue- and Inducer-specific Manner* , 1998, The Journal of Biological Chemistry.

[4]  I. Bojesen,et al.  Nature of the Elements Transporting Long-Chain Fatty Acids Through the Red Cell Membrane , 1998, The Journal of Membrane Biology.

[5]  E. Richter,et al.  Contraction-induced increase in Vmax of palmitate uptake and oxidation in perfused skeletal muscle. , 1998, Journal of applied physiology.

[6]  D. Bernlohr,et al.  Physiological properties and functions of intracellular fatty acid-binding proteins. , 1998, Biochimica et biophysica acta.

[7]  J. Hamilton Fatty acid transport: difficult or easy? , 1998, Journal of lipid research.

[8]  Kenneth R Feingold,et al.  Regulation of fatty acid transport protein and fatty acid translocase mRNA levels by endotoxin and cytokines. , 1998, American journal of physiology. Endocrinology and metabolism.

[9]  A. Kleinfeld,et al.  Transport of long-chain native fatty acids across lipid bilayer membranes indicates that transbilayer flip-flop is rate limiting. , 1997, Biochemistry.

[10]  C. Galli,et al.  Recent advances in the biology of n-6 fatty acids. , 1997, Nutrition.

[11]  G. J. van der Vusse,et al.  Molecular cloning of fatty acid-transport protein cDNA from rat. , 1997, Biochimica et biophysica acta.

[12]  F. V. van Nieuwenhoven,et al.  Role of membrane-associated and cytoplasmic fatty acid-binding proteins in cellular fatty acid metabolism. , 1997, Prostaglandins, leukotrienes, and essential fatty acids.

[13]  M. Lisanti,et al.  Association of Phosphofructokinase-M with Caveolin-3 in Differentiated Skeletal Myotubes , 1997, The Journal of Biological Chemistry.

[14]  P. Grimaldi,et al.  Regulation of FAT/CD36 gene expression: further evidence in support of a role of the protein in fatty acid binding/transport. , 1997, Prostaglandins, leukotrienes, and essential fatty acids.

[15]  A. Yamashita,et al.  Acyltransferases and transacylases involved in fatty acid remodeling of phospholipids and metabolism of bioactive lipids in mammalian cells. , 1997, Journal of biochemistry.

[16]  Y. Owada,et al.  Localization of mRNA for fatty acid transport protein in developing and mature brain of rats. , 1997, Brain research. Molecular brain research.

[17]  A. Kleinfeld,et al.  Flip-flop is slow and rate limiting for the movement of long chain anthroyloxy fatty acids across lipid vesicles. , 1997, Biochemistry.

[18]  M. J. Mueller,et al.  Protein-facilitated Export of Arachidonic Acid from Pig Neutrophils* , 1997, The Journal of Biological Chemistry.

[19]  F. V. van Nieuwenhoven,et al.  Uptake and metabolism of palmitate by isolated cardiac myocytes from adult rats: involvement of sarcolemmal proteins. , 1997, Journal of lipid research.

[20]  P. Black,et al.  Disruption of the Saccharomyces cerevisiae Homologue to the Murine Fatty Acid Transport Protein Impairs Uptake and Growth on Long-chain Fatty Acids* , 1997, The Journal of Biological Chemistry.

[21]  D. Stump,et al.  Uptake of Long Chain Free Fatty Acids Is Selectively Up-regulated in Adipocytes of Zucker Rats with Genetic Obesity and Non-insulin-dependent Diabetes Mellitus* , 1997, The Journal of Biological Chemistry.

[22]  E. Richter,et al.  Membrane associated fatty acid binding protein (FABPpm) in human skeletal muscle is increased by endurance training. , 1997, Biochemical and biophysical research communications.

[23]  F. Kamp,et al.  Dissociation of long and very long chain fatty acids from phospholipid bilayers. , 1996, Biochemistry.

[24]  T. Aoyama,et al.  Molecular Cloning of cDNA Encoding Rat Very Long-chain Acyl-CoA Synthetase* , 1996, The Journal of Biological Chemistry.

[25]  N. Abumrad,et al.  Reversible Binding of Long-chain Fatty Acids to Purified FAT, the Adipose CD36 Homolog , 1996, The Journal of Membrane Biology.

[26]  G. J. van der Vusse,et al.  Cellular fatty acid-binding proteins: their function and physiological significance. , 1996, Progress in lipid research.

[27]  H. Lodish,et al.  Regulation of the murine adipocyte fatty acid transporter gene by insulin. , 1996, Molecular endocrinology.

[28]  J. Storch,et al.  Fatty Acid Transfer from Liver and Intestinal Fatty Acid-binding Proteins to Membranes Occurs by Different Mechanisms* , 1996, The Journal of Biological Chemistry.

[29]  P. Besnard,et al.  Localization and regulation of the putative membrane fatty-acid transporter (FAT) in the small intestine. Comparison with fatty acid-binding proteins (FABP). , 1996, European journal of biochemistry.

[30]  D. Zakim Fatty Acids Enter Cells by Simple Diffusion , 1996, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[31]  P. Grimaldi,et al.  Expression of the CD36 homolog (FAT) in fibroblast cells: effects on fatty acid transport. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[32]  A. Fahr,et al.  Irreversible inhibition of hepatic fatty acid salt uptake by photoaffinity labeling with 11, 11-azistearate. , 1996, Journal of lipid research.

[33]  D. Stump,et al.  Oleate uptake by isolated hepatocytes and the perfused rat liver is competitively inhibited by palmitate. , 1996, The American journal of physiology.

[34]  J. Storch,et al.  Fatty acid uptake by Caco-2 human intestinal cells. , 1996, Journal of lipid research.

[35]  I. Bojesen,et al.  Specificities of Red Cell Membrane Sites Transporting Three Long Chain Fatty Acids , 1996, The Journal of Membrane Biology.

[36]  D. Zakim,et al.  Fatty acid flip-flop in phospholipid bilayers is extremely fast. , 1995, Biochemistry.

[37]  D. Greenwalt,et al.  Heart CD36 expression is increased in murine models of diabetes and in mice fed a high fat diet. , 1995, The Journal of clinical investigation.

[38]  D. Mundy Protein palmitoylation in membrane trafficking. , 1995, Biochemical Society transactions.

[39]  K. Kawamura,et al.  Isolation of myocardial membrane long-chain fatty acid-binding protein: homology with a rat membrane protein implicated in the binding or transport of long-chain fatty acids. , 1995, Journal of molecular and cellular cardiology.

[40]  M. Bouvier,et al.  Dynamic regulation of G-protein coupled receptor palmitoylation: potential role in receptor function. , 1995, Biochemical Society transactions.

[41]  K. Kawamura,et al.  Effect of sulfo-N-succinimidyl palmitate on the rat heart: myocardial long-chain fatty acid uptake and cardiac hypertrophy. , 1995, Journal of molecular and cellular cardiology.

[42]  G. Milligan,et al.  Dynamic protein acylation and the regulation of localization and function of signal-transducing proteins. , 1995, Biochemical Society transactions.

[43]  G. V. van Eys,et al.  Putative membrane fatty acid translocase and cytoplasmic fatty acid-binding protein are co-expressed in rat heart and skeletal muscles. , 1995, Biochemical and biophysical research communications.

[44]  G. Ailhaud,et al.  Cloning of a Protein That Mediates Transcriptional Effects of Fatty Acids in Preadipocytes , 1995, The Journal of Biological Chemistry.

[45]  A. Kleinfeld,et al.  Unbound free fatty acid levels in human serum. , 1995, Journal of lipid research.

[46]  G. Ailhaud,et al.  Fatty acids and adipose cell differentiation. , 1995, Prostaglandins, leukotrienes, and essential fatty acids.

[47]  H. Lodish,et al.  Expression cloning and characterization of a novel adipocyte long chain fatty acid transport protein , 1994, Cell.

[48]  R. G. Anderson Functional specialization of the glycosylphosphatidylinositol membrane anchor. , 1994, Seminars in immunology.

[49]  D. Stump,et al.  Constitutive expression of a saturable transport system for non-esterified fatty acids in Xenopus laevis oocytes. , 1994, The Biochemical journal.

[50]  D. Matthews,et al.  Effect of endurance training on plasma free fatty acid turnover and oxidation during exercise. , 1993, The American journal of physiology.

[51]  P. Grimaldi,et al.  Cloning of a rat adipocyte membrane protein implicated in binding or transport of long-chain fatty acids that is induced during preadipocyte differentiation. Homology with human CD36. , 1993, The Journal of biological chemistry.

[52]  A. Kleinfeld,et al.  Transfer of long-chain fluorescent fatty acids between small and large unilamellar vesicles. , 1993, Biochemistry.

[53]  P. Berk,et al.  Hepatic Transport and Bile Secretion: Physiology and Pathophysiology , 1992 .

[54]  P. Grimaldi,et al.  Induction of aP2 gene expression by nonmetabolized long-chain fatty acids. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[55]  N. Abumrad,et al.  Labelling of an 88 kDa adipocyte membrane protein by sulpho-N-succinimidyl long-chain fatty acids: inhibition of fatty acid transport. , 1992, Biochemical Society transactions.

[56]  Hyung-Gu Kim,et al.  Mechanism of free fatty acid transfer from rat heart fatty acid-binding protein to phospholipid membranes. Evidence for a collisional process. , 1992, The Journal of biological chemistry.

[57]  R. Reneman,et al.  Fatty acid homeostasis in the normoxic and ischemic heart. , 1992, Physiological reviews.

[58]  D. Stump,et al.  Adipocyte differentiation of 3T3-L1 cells involves augmented expression of a 43-kDa plasma membrane fatty acid-binding protein. , 1992, The Journal of biological chemistry.

[59]  A. O. Pedersen,et al.  Solubility of long-chain fatty acids in phosphate buffer at pH 7.4. , 1992, Biochimica et biophysica acta.

[60]  E. Richter,et al.  Increased plasma FFA uptake and oxidation during prolonged exercise in trained vs. untrained humans. , 1992, The American journal of physiology.

[61]  N. Abumrad,et al.  Glycerolipid synthesis in isolated adipocytes: substrate dependence and influence of norepinephrine. , 1992, Journal of lipid research.

[62]  B. Spiegelman,et al.  Fatty acid regulation of gene expression. Transcriptional and post-transcriptional mechanisms. , 1992, The Journal of biological chemistry.

[63]  S. Corey,et al.  Unsaturated fatty acids and lipoxygenase products regulate phagocytic NADPH oxidase activity by a nondetergent mechanism. , 1991, The Journal of laboratory and clinical medicine.

[64]  G. Ailhaud,et al.  Regulation of adipose cell differentiation. I. Fatty acids are inducers of the aP2 gene expression. , 1991, Journal of lipid research.

[65]  A. Kleinfeld,et al.  Direct determination of free fatty acid transport across the adipocyte plasma membrane using quantitative fluorescence microscopy. , 1991, The Journal of biological chemistry.

[66]  R. Ordway,et al.  Direct regulation of ion channels by fatty acids , 1991, Trends in Neurosciences.

[67]  M. Welsh,et al.  Fatty acids inhibit apical membrane chloride channels in airway epithelia. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[68]  P. Calder,et al.  Uptake and incorporation of saturated and unsaturated fatty acids into macrophage lipids and their effect upon macrophage adhesion and phagocytosis. , 1990, The Biochemical journal.

[69]  D. Stump,et al.  Plasma membrane fatty acid-binding protein and mitochondrial glutamic-oxaloacetic transaminase of rat liver are related. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[70]  M. Trimble Mediated transport of long-chain fatty acids by rat renal basolateral membranes. , 1989, The American journal of physiology.

[71]  R. Robinson,et al.  At physiologic albumin/oleate concentrations oleate uptake by isolated hepatocytes, cardiac myocytes, and adipocytes is a saturable function of the unbound oleate concentration. Uptake kinetics are consistent with the conventional theory. , 1989, The Journal of clinical investigation.

[72]  S. Nandi,et al.  Phospholipids containing polyunsaturated fatty acyl groups are mitogenic for normal mouse mammary epithelial cells in serum-free primary cell culture. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[73]  W. Stremmel Fatty acid uptake by isolated rat heart myocytes represents a carrier-mediated transport process. , 1988, The Journal of clinical investigation.

[74]  W. Stremmel,et al.  Hepatocellular influx of [14C]oleate reflects membrane transport rather than intracellular metabolism or binding. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[75]  D. Zakim,et al.  Physical-chemical model for the entry of water-insoluble compounds into cells. Studies of fatty acid uptake by the liver. , 1986, Biochemistry.

[76]  A. Kleinfeld,et al.  Transfer of long-chain fluorescent free fatty acids between unilamellar vesicles. , 1986, Biochemistry.

[77]  N. Abumrad,et al.  Increased affinity predominates in insulin stimulation of glucose transport in the adipocyte. , 1985, The Journal of biological chemistry.

[78]  C. Park,et al.  Permeation of long-chain fatty acid into adipocytes. Kinetics, specificity, and evidence for involvement of a membrane protein. , 1984, The Journal of biological chemistry.

[79]  C. Park,et al.  Mechanism of long chain fatty acid permeation in the isolated adipocyte. , 1981, The Journal of biological chemistry.

[80]  B. Jeanrenaud,et al.  Potential mechanism of insulin action on glucose transport in the isolated rat diaphragm. Apparent translocation of intracellular transport units to the plasma membrane. , 1981, The Journal of biological chemistry.

[81]  G. Dudley,et al.  Uptake of chylomicron triglycerides by contracting skeletal muscle in rats. , 1980, Journal of applied physiology: respiratory, environmental and exercise physiology.

[82]  T. Kôno,et al.  Evidence that insulin causes translocation of glucose transport activity to the plasma membrane from an intracellular storage site. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[83]  H. Pownall,et al.  Mechanism and kinetics of transfer of a fluorescent fatty acid between single-walled phosphatidylcholine vesicles. , 1980, Biochemistry.

[84]  H. Goodman,et al.  Efflux of free fatty acids from adipose tissue. , 1971, The American journal of physiology.

[85]  D. Steinberg,et al.  UPTAKE OF FREE FATTY ACIDS BY EHRLICH ASCITES TUMOR CELLS. , 1965, The Journal of biological chemistry.

[86]  D. Goodman,et al.  The Interaction of Human Serum Albumin with Long-chain Fatty Acid Anions , 1958 .

[87]  R. Bing,et al.  Metabolism of the human heart. II. Studies on fat, ketone and amino acid metabolism. , 1954, The American journal of medicine.

[88]  J. Peters,et al.  Expression of putative fatty acid transporter genes are regulated by peroxisome proliferator-activated receptor alpha and gamma activators in a tissue- and inducer-specific manner. , 1998, The Journal of biological chemistry.

[89]  K. Kawamura,et al.  Is CD36 deficiency an etiology of hereditary hypertrophic cardiomyopathy? , 1997, Journal of molecular and cellular cardiology.

[90]  P. Calder,et al.  n-3 polyunsaturated fatty acids and cytokine production in health and disease. , 1997, Annals of nutrition & metabolism.

[91]  M. Gordon,et al.  Arachidonic acid uptake by human platelets is mediated by CD36. , 1996, Platelets.

[92]  E. Matitashvili,et al.  Association and coexpression of fatty-acid-binding protein and glycoprotein CD36 in the bovine mammary gland. , 1995, European journal of biochemistry.

[93]  G. Ailhaud Regulation of gene expression by fatty acids in the adipose cell. , 1993, Prostaglandins, leukotrienes, and essential fatty acids.

[94]  P. Calder,et al.  The inhibition of T-lymphocyte proliferation by fatty acids is via an eicosanoid-independent mechanism. , 1992, Immunology.

[95]  A. Kleinfeld Transport of free fatty acids across membranes , 1990 .

[96]  D. Cistola,et al.  Transfer of oleic acid between albumin and phospholipid vesicles. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[97]  W. Stremmel,et al.  Isolation and partial characterization of a fatty acid binding protein in rat liver plasma membranes. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[98]  S. Cushman,et al.  Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. Apparent translocation of intracellular transport systems to the plasma membrane. , 1980, The Journal of biological chemistry.

[99]  A. A. Spector,et al.  Binding of long-chain fatty acids to bovine serum albumin. , 1969, Journal of lipid research.