fatty acid transport proteins

Summary

Summary: A broad category of membrane transport proteins that specifically transport FREE FATTY ACIDS across cellular membranes. They play an important role in LIPID METABOLISM in CELLS that utilize free fatty acids as an energy source.

Top Publications

  1. Holloway G, Chou C, Lally J, Stellingwerff T, Maher A, Gavrilova O, et al. Increasing skeletal muscle fatty acid transport protein 1 (FATP1) targets fatty acids to oxidation and does not predispose mice to diet-induced insulin resistance. Diabetologia. 2011;54:1457-67 pubmed publisher
    ..Therefore, skeletal muscle FATP1 overabundance does not predispose animals to diet-induced insulin resistance. ..
  2. Shim J, Moulson C, Newberry E, Lin M, Xie Y, Kennedy S, et al. Fatty acid transport protein 4 is dispensable for intestinal lipid absorption in mice. J Lipid Res. 2009;50:491-500 pubmed publisher
    ..Taken together, our studies find no evidence for a physiological role of intestinal FATP4 in dietary lipid absorption in mice. ..
  3. Zhou W, Madrid P, Fluitt A, Stahl A, Xie X. Development and validation of a high-throughput screening assay for human long-chain fatty acid transport proteins 4 and 5. J Biomol Screen. 2010;15:488-97 pubmed publisher
    Dietary long-chain fatty acid (LCFA) uptake across cell membranes is mediated principally by fatty acid transport proteins (FATPs). Six subtypes of this transporter are differentially expressed throughout the human and rodent body...
  4. Hall A, Smith A, Bernlohr D. Characterization of the Acyl-CoA synthetase activity of purified murine fatty acid transport protein 1. J Biol Chem. 2003;278:43008-13 pubmed
    ..These findings are consistent with the hypothesis that that fatty acid uptake into cells is linked to their esterification with coenzyme A. ..
  5. Marotta M, Ferrer Martnez A, Parnau J, Turini M, Mace K, Gómez Foix A. Fiber type- and fatty acid composition-dependent effects of high-fat diets on rat muscle triacylglyceride and fatty acid transporter protein-1 content. Metabolism. 2004;53:1032-6 pubmed
    ..Hypercaloric saturated, monounsaturated, or n-6 polyunsaturated lipid diets cause equivalent whole body insulin resistance in rats, but only an n-6 polyunsaturated acid-based diet triggers intramuscular TAG accumulation. ..
  6. Jia Z, Moulson C, Pei Z, Miner J, Watkins P. Fatty acid transport protein 4 is the principal very long chain fatty acyl-CoA synthetase in skin fibroblasts. J Biol Chem. 2007;282:20573-83 pubmed
    ..FATP4-deficient cells also contained abnormal neutral lipid droplets. These additional defects indicate that metabolic abnormalities in these cells are not limited to very long chain fatty acids. ..
  7. Doege H, Stahl A. Protein-mediated fatty acid uptake: novel insights from in vivo models. Physiology (Bethesda). 2006;21:259-68 pubmed
    Long-chain fatty acids are both important metabolites as well as signaling molecules. Fatty acid transport proteins are key mediators of cellular fatty acid uptake and recent transgenic and knockout animal models have provided new ..
  8. Hubbard B, Doege H, Punreddy S, Wu H, Huang X, Kaushik V, et al. Mice deleted for fatty acid transport protein 5 have defective bile acid conjugation and are protected from obesity. Gastroenterology. 2006;130:1259-69 pubmed
    ..FATP5 deletion mice provide a new model to study the intersection of bile acid metabolism, lipid metabolism, and body weight regulation. ..
  9. Doege H, Grimm D, Falcon A, Tsang B, Storm T, Xu H, et al. Silencing of hepatic fatty acid transporter protein 5 in vivo reverses diet-induced non-alcoholic fatty liver disease and improves hyperglycemia. J Biol Chem. 2008;283:22186-92 pubmed publisher

More Information

Publications62

  1. Armbrust S, Hoffmann R, Jochum F, Neumann L, Fusch C. Restrictive dermopathy associated with transposition of the great arteries and microcolon: a rare neonatal entity with new symptoms. Arch Dermatol. 2005;141:611-3 pubmed
    ..Whether the left transposition of the great artery is associated with restrictive dermopathy or represents an additional malformation of multifactorial, polygenetic, or monogenetic cause remains open. ..
  2. Garcia Martinez C, Marotta M, Moore Carrasco R, Guitart M, Camps M, Busquets S, et al. Impact on fatty acid metabolism and differential localization of FATP1 and FAT/CD36 proteins delivered in cultured human muscle cells. Am J Physiol Cell Physiol. 2005;288:C1264-72 pubmed
    ..Overall, both FATP1 and FAT stimulated transport and consumption of palmitate and oleate, which they channeled away from complete oxidation and toward TAG synthesis. ..
  3. Johnson A, Stahl A, Zager R. Triglyceride accumulation in injured renal tubular cells: alterations in both synthetic and catabolic pathways. Kidney Int. 2005;67:2196-209 pubmed
    ..Simple flux of excess FFAs into triglyceride pools is an overly simplistic view of the post-injury-triglyceride loading state. ..
  4. DiRusso C, Li H, Darwis D, Watkins P, Berger J, Black P. Comparative biochemical studies of the murine fatty acid transport proteins (FATP) expressed in yeast. J Biol Chem. 2005;280:16829-37 pubmed
    ..These data support the conclusion that the different mmFATP isoforms play unique roles in fatty acid trafficking, including the transport of exogenous long-chain fatty acids. ..
  5. van den Berg B, Black P, Clemons W, Rapoport T. Crystal structure of the long-chain fatty acid transporter FadL. Science. 2004;304:1506-9 pubmed
    ..The structures suggest that hydrophobic compounds bind to multiple sites in FadL and use a transport mechanism that involves spontaneous conformational changes in the hatch. ..
  6. Glatz J, Luiken J, Bonen A. Membrane fatty acid transporters as regulators of lipid metabolism: implications for metabolic disease. Physiol Rev. 2010;90:367-417 pubmed publisher
    ..As a result, membrane fatty acid transporters are now being regarded as a promising therapeutic target to redirect lipid fluxes in the body in an organ-specific fashion. ..
  7. Stahl A, Hirsch D, Gimeno R, Punreddy S, Ge P, Watson N, et al. Identification of the major intestinal fatty acid transport protein. Mol Cell. 1999;4:299-308 pubmed
    ..This suggests that FATP4 is the principal fatty acid transporter in enterocytes and may constitute a novel target for antiobesity therapy. ..
  8. Hall A, Wiczer B, Herrmann T, Stremmel W, Bernlohr D. Enzymatic properties of purified murine fatty acid transport protein 4 and analysis of acyl-CoA synthetase activities in tissues from FATP4 null mice. J Biol Chem. 2005;280:11948-54 pubmed
  9. Doege H, Baillie R, Ortegon A, Tsang B, Wu Q, Punreddy S, et al. Targeted deletion of FATP5 reveals multiple functions in liver metabolism: alterations in hepatic lipid homeostasis. Gastroenterology. 2006;130:1245-58 pubmed
    ..These new insights into the physiological role of FATP5 should lead to an improved understanding of liver function and disease. ..
  10. Herrmann T, Grone H, Langbein L, Kaiser I, Gosch I, Bennemann U, et al. Disturbed epidermal structure in mice with temporally controlled fatp4 deficiency. J Invest Dermatol. 2005;125:1228-35 pubmed
    ..These changes resemble the histological abnormalities in the epidermis of newborn mice with total Fatp4 deficiency. We conclude that Fatp4 in epidermal keratinocytes is essential for the maintenance of a normal epidermal structure. ..
  11. Chabowski A, Gorski J, Calles Escandon J, Tandon N, Bonen A. Hypoxia-induced fatty acid transporter translocation increases fatty acid transport and contributes to lipid accumulation in the heart. FEBS Lett. 2006;580:3617-23 pubmed
  12. Bionaz M, Loor J. ACSL1, AGPAT6, FABP3, LPIN1, and SLC27A6 are the most abundant isoforms in bovine mammary tissue and their expression is affected by stage of lactation. J Nutr. 2008;138:1019-24 pubmed
    ..Results suggest that SLC27A6, ACSL1, FABP3, AGPAT6, and LPIN1 coordinately regulate the channeling of fatty acids toward copious milk fat synthesis in bovine mammary. ..
  13. Gertow K, Pietiläinen K, Yki Jarvinen H, Kaprio J, Rissanen A, Eriksson P, et al. Expression of fatty-acid-handling proteins in human adipose tissue in relation to obesity and insulin resistance. Diabetologia. 2004;47:1118-25 pubmed
    ..Our results suggest that facilitated fatty acid trafficking is a physiologically and pathologically relevant phenomenon in man. ..
  14. Gimeno R, Ortegon A, Patel S, Punreddy S, Ge P, Sun Y, et al. Characterization of a heart-specific fatty acid transport protein. J Biol Chem. 2003;278:16039-44 pubmed
    ..These findings suggest that FATP6 is involved in heart LCFA uptake, in which it may play a role in the pathogenesis of lipid-related cardiac disorders. ..
  15. Larque E, Krauss Etschmann S, Campoy C, Hartl D, Linde J, Klingler M, et al. Docosahexaenoic acid supply in pregnancy affects placental expression of fatty acid transport proteins. Am J Clin Nutr. 2006;84:853-61 pubmed
  16. Chabowski A, Zmijewska M, Gorski J, Bonen A, Kaminski K, Kozuch M, et al. IL-6 deficiency increases fatty acid transporters and intramuscular lipid content in red but not white skeletal muscle. J Physiol Pharmacol. 2008;59 Suppl 7:105-17 pubmed
    ..IL-6 ablation increases fatty acid transporter expression and intramuscular lipid accumulation, particularly the saturated fatty acids. These effects however were confined to oxidative muscles, as glycolytic muscles were not affected. ..
  17. Herrmann T, Buchkremer F, Gosch I, Hall A, Bernlohr D, Stremmel W. Mouse fatty acid transport protein 4 (FATP4): characterization of the gene and functional assessment as a very long chain acyl-CoA synthetase. Gene. 2001;270:31-40 pubmed
  18. Knipp G, Liu B, Audus K, Fujii H, Ono T, Soares M. Fatty acid transport regulatory proteins in the developing rat placenta and in trophoblast cell culture models. Placenta. 2000;21:367-75 pubmed
    ..The predominant expression of hFABP and FAT in the labyrinth zone of the chorioallantoic placenta implicates hFABP and FAT in the transplacental movement of fatty acids from maternal to fetal compartments. ..
  19. Moulson C, Martin D, Lugus J, Schaffer J, Lind A, Miner J. Cloning of wrinkle-free, a previously uncharacterized mouse mutation, reveals crucial roles for fatty acid transport protein 4 in skin and hair development. Proc Natl Acad Sci U S A. 2003;100:5274-9 pubmed
    ..However, its function in vivo had not been determined. Our results demonstrate an unexpected yet critical role for FATP4 in skin and hair development and suggest Slc27a4 to be a candidate gene for restrictive dermopathy. ..
  20. Stuhlsatz Krouper S, Bennett N, Schaffer J. Substitution of alanine for serine 250 in the murine fatty acid transport protein inhibits long chain fatty acid transport. J Biol Chem. 1998;273:28642-50 pubmed
    ..These results are consistent with a mechanism of action for FATP involving ATP binding that is dependent on serine 250 of the IYTSGTTGXPK motif. ..
  21. Richards M, Harp J, Ory D, Schaffer J. Fatty acid transport protein 1 and long-chain acyl coenzyme A synthetase 1 interact in adipocytes. J Lipid Res. 2006;47:665-72 pubmed
    The fatty acid transport proteins (FATP) and long-chain acyl coenzyme A synthetase (ACSL) proteins have been shown to play a role in facilitating long-chain fatty acid (LCFA) transport in mammalian cells under physiologic conditions...
  22. Watkins P. Very-long-chain acyl-CoA synthetases. J Biol Chem. 2008;283:1773-7 pubmed
  23. Kazantzis M, Stahl A. Fatty acid transport proteins, implications in physiology and disease. Biochim Biophys Acta. 2012;1821:852-7 pubmed publisher
    ..muscle, heart, and liver, has been shown to be protein mediated and various unique combinations of fatty acid transport proteins (FATPs/SLC27A1-6) are expressed by all of these tissues...
  24. Hui T, Frohnert B, Smith A, Schaffer J, Bernlohr D. Characterization of the murine fatty acid transport protein gene and its insulin response sequence. J Biol Chem. 1998;273:27420-9 pubmed
    ..These results characterize the murine FATP gene and its insulin responsiveness as well as present a framework for future studies of its role in lipid metabolism, obesity, and type II diabetes mellitus. ..
  25. Moulson C, Lin M, White J, Newberry E, Davidson N, Miner J. Keratinocyte-specific expression of fatty acid transport protein 4 rescues the wrinkle-free phenotype in Slc27a4/Fatp4 mutant mice. J Biol Chem. 2007;282:15912-20 pubmed
    ..We conclude that expression of FATP4 with an intact acyl-CoA synthetase domain in suprabasal keratinocytes is necessary for normal skin development and that FATP4 functions in establishing the cornified envelope. ..
  26. Stahl A. A current review of fatty acid transport proteins (SLC27). Pflugers Arch. 2004;447:722-7 pubmed
    ..b>Fatty acid transport proteins (FATPs/solute carrier family 27) are integral transmembrane proteins that enhance the uptake of long-..
  27. Talanian J, Holloway G, Snook L, Heigenhauser G, Bonen A, Spriet L. Exercise training increases sarcolemmal and mitochondrial fatty acid transport proteins in human skeletal muscle. Am J Physiol Endocrinol Metab. 2010;299:E180-8 pubmed publisher
    ..across these membranes is recognized to be primarily protein mediated, limited by the abundance of fatty acid transport proteins on the respective membranes...
  28. Jain S, Chabowski A, Snook L, Schwenk R, Glatz J, Luiken J, et al. Additive effects of insulin and muscle contraction on fatty acid transport and fatty acid transporters, FAT/CD36, FABPpm, FATP1, 4 and 6. FEBS Lett. 2009;583:2294-300 pubmed publisher
    ..Insulin and muscle contraction increased plasmalemmal FAT/CD36, FABPpm, FATP1, and FATP4, but not FATP6. Only FAT/CD36 and FATP1 were stimulated in an additive manner by insulin and by muscle contraction. ..
  29. Black P, DiRusso C. Transmembrane movement of exogenous long-chain fatty acids: proteins, enzymes, and vectorial esterification. Microbiol Mol Biol Rev. 2003;67:454-72, table of contents pubmed
    ..In both systems, central players in the process of fatty acid transport are fatty acid transport proteins (FadL or Fat1p) and fatty acyl coenzyme A (CoA) synthetase (FACS; fatty acid CoA ligase [AMP forming] [..
  30. Guignard T, Jin M, Pequignot M, Li S, Chassigneux Y, Chekroud K, et al. FATP1 inhibits 11-cis retinol formation via interaction with the visual cycle retinoid isomerase RPE65 and lecithin:retinol acyltransferase. J Biol Chem. 2010;285:18759-68 pubmed publisher
    ..The identification of this new visual cycle inhibitory component in RPE may contribute to further understanding of retinal pathogenesis...
  31. Auinger A, Valenti L, Pfeuffer M, Helwig U, Herrmann J, Fracanzani A, et al. A promoter polymorphism in the liver-specific fatty acid transport protein 5 is associated with features of the metabolic syndrome and steatosis. Horm Metab Res. 2010;42:854-9 pubmed publisher
    ..The impact of the BMI on the severity of steatosis in NAFLD cases seems to depend on the FATP5 polymorphism. ..
  32. Sanchez Gurmaches J, Østbye T, Navarro I, Torgersen J, Hevrøy E, Ruyter B, et al. In vivo and in vitro insulin and fasting control of the transmembrane fatty acid transport proteins in Atlantic salmon (Salmo salar). Am J Physiol Regul Integr Comp Physiol. 2011;301:R947-57 pubmed publisher
    ..Overall, Atlantic salmon FA transporters are regulated by fasting and insulin on in vivo and in vitro models...
  33. Klar J, Schweiger M, Zimmerman R, Zechner R, Li H, Torma H, et al. Mutations in the fatty acid transport protein 4 gene cause the ichthyosis prematurity syndrome. Am J Hum Genet. 2009;85:248-53 pubmed publisher
    ..Our results further emphasize the importance of fatty acid metabolism for normal epidermal barrier function illustrated by deficiency of a member in the FATP family of proteins. ..
  34. Schmuth M, Ortegon A, Mao Qiang M, Elias P, Feingold K, Stahl A. Differential expression of fatty acid transport proteins in epidermis and skin appendages. J Invest Dermatol. 2005;125:1174-81 pubmed
    ..Plasma membrane proteins can significantly contribute to the latter process. In particular, fatty acid transport proteins (FATP/solute carrier family 27) are integral transmembrane proteins that enhance the uptake of long-..
  35. Wu Q, Kazantzis M, Doege H, Ortegon A, Tsang B, Falcon A, et al. Fatty acid transport protein 1 is required for nonshivering thermogenesis in brown adipose tissue. Diabetes. 2006;55:3229-37 pubmed
    ..Stimulation of fatty uptake by isoproterenol required both protein kinase A and mitogen-activated kinase signaling and is completely dependent on FATP1 expression, as small-hairpin RNA-mediated knock down of FATP1 abrogated the effect. ..
  36. Higashitani A, Nishimura Y, Hara H, Aiba H, Mizuno T, Horiuchi K. Osmoregulation of the fatty acid receptor gene fadL in Escherichia coli. Mol Gen Genet. 1993;240:339-47 pubmed
    ..These results suggest that transcription of the fadL gene is osmotically regulated by the OmpR-EnvZ two-component system. ..
  37. Pohl J, Ring A, Ehehalt R, Herrmann T, Stremmel W. New concepts of cellular fatty acid uptake: role of fatty acid transport proteins and of caveolae. Proc Nutr Soc. 2004;63:259-62 pubmed
    ..Amongst these proteins is a family of membrane-associated proteins termed fatty acid transport proteins (FATP). So far six members of this family, designated FATP 1-6, have been characterized...
  38. DiRusso C, Metzger A, Heimert T. Regulation of transcription of genes required for fatty acid transport and unsaturated fatty acid biosynthesis in Escherichia coli by FadR. Mol Microbiol. 1993;7:311-22 pubmed
    ..We demonstrated repression of fadL transcription and activation of fabA transcription in vitro using run-off transcription assays containing purified FadR and RNA polymerase. ..
  39. Berger J, Truppe C, Neumann H, Forss Petter S. A novel relative of the very-long-chain acyl-CoA synthetase and fatty acid transporter protein genes with a distinct expression pattern. Biochem Biophys Res Commun. 1998;247:255-60 pubmed
    ..2 kb). In heart, but not in kidney, transcripts undetectable by Northern blot analysis could be demonstrated by RT PCR. Southern blot analysis indicated single-copy VLACSR genes in the mouse and human genomes. ..
  40. Lewis S, Listenberger L, Ory D, Schaffer J. Membrane topology of the murine fatty acid transport protein 1. J Biol Chem. 2001;276:37042-50 pubmed
    ..This study provides the first experimental evidence for topology of a member of the family of plasma membrane fatty acid transport proteins.
  41. Herrmann T, van der Hoeven F, Grone H, Stewart A, Langbein L, Kaiser I, et al. Mice with targeted disruption of the fatty acid transport protein 4 (Fatp 4, Slc27a4) gene show features of lethal restrictive dermopathy. J Cell Biol. 2003;161:1105-15 pubmed
    ..These findings reveal a previously unknown, essential function of Fatp4 in the formation of the epidermal barrier. ..
  42. Gimeno R, Hirsch D, Punreddy S, Sun Y, Ortegon A, Wu H, et al. Targeted deletion of fatty acid transport protein-4 results in early embryonic lethality. J Biol Chem. 2003;278:49512-6 pubmed
    ..This localization is consistent with a role for FATP4 in fat absorption in early embryogenesis and suggests a novel requirement for FATP4 function during development. ..
  43. Wiczer B, Bernlohr D. A novel role for fatty acid transport protein 1 in the regulation of tricarboxylic acid cycle and mitochondrial function in 3T3-L1 adipocytes. J Lipid Res. 2009;50:2502-13 pubmed publisher
    b>Fatty acid transport proteins (FATPs) are integral membrane acyl-CoA synthetases implicated in adipocyte fatty acid influx and esterification...
  44. Nickerson J, Alkhateeb H, Benton C, Lally J, Nickerson J, Han X, et al. Greater transport efficiencies of the membrane fatty acid transporters FAT/CD36 and FATP4 compared with FABPpm and FATP1 and differential effects on fatty acid esterification and oxidation in rat skeletal muscle. J Biol Chem. 2009;284:16522-30 pubmed publisher
    ..In vivo, FAT/CD36 and FATP4 are the most effective fatty acid transporters, whereas FABPpm and FAT/CD36 are key for stimulating fatty acid oxidation. ..
  45. Pelsers M, Stellingwerff T, van Loon L. The role of membrane fatty-acid transporters in regulating skeletal muscle substrate use during exercise. Sports Med. 2008;38:387-99 pubmed
    ..This article will provide an overview on the effects of diet, acute exercise and exercise training on the expression and/or translocation of the various LCFA transporters in skeletal muscle tissue (FAT/CD36, FABPpm, FATP). ..
  46. Wang Q, Herrera Ruiz D, Mathis A, Cook T, Bhardwaj R, Knipp G. Expression of PPAR, RXR isoforms and fatty acid transporting proteins in the rat and human gastrointestinal tracts. J Pharm Sci. 2005;94:363-72 pubmed
    ..These results provide a physiological foundation for rational drug design and drug delivery for the mitigation of metabolic syndrome and associated disorders to normalize intestinal FA absorption. ..
  47. Chiu H, Kovacs A, Blanton R, Han X, Courtois M, Weinheimer C, et al. Transgenic expression of fatty acid transport protein 1 in the heart causes lipotoxic cardiomyopathy. Circ Res. 2005;96:225-33 pubmed
    ..Moreover, the MHC-FATP model supports a role for FATPs in FFA import into the heart in vivo. ..
  48. Richards M, Listenberger L, Kelly A, Lewis S, Ory D, Schaffer J. Oligomerization of the murine fatty acid transport protein 1. J Biol Chem. 2003;278:10477-83 pubmed
    ..Taken together, these results are consistent with a model in which FATP1 homodimeric complexes play an important role in cellular fatty acid import. ..
  49. Stremmel W, Pohl L, Ring A, Herrmann T. A new concept of cellular uptake and intracellular trafficking of long-chain fatty acids. Lipids. 2001;36:981-9 pubmed
    ..For this process, the family of fatty acid transport proteins (FATP 1-5/6) might be relevant because they have been shown to possess acyl-CoA synthetase activity...
  50. Chabowski A, Coort S, Calles Escandon J, Tandon N, Glatz J, Luiken J, et al. The subcellular compartmentation of fatty acid transporters is regulated differently by insulin and by AICAR. FEBS Lett. 2005;579:2428-32 pubmed
  51. Hirsch D, Stahl A, Lodish H. A family of fatty acid transporters conserved from mycobacterium to man. Proc Natl Acad Sci U S A. 1998;95:8625-9 pubmed
  52. Digel M, Staffer S, Ehehalt F, Stremmel W, Ehehalt R, Fullekrug J. FATP4 contributes as an enzyme to the basal and insulin-mediated fatty acid uptake of C?C?? muscle cells. Am J Physiol Endocrinol Metab. 2011;301:E785-96 pubmed publisher
    ..We conclude that FATP4 functions by its intrinsic enzymatic activity. This is in line with the concept that intracellular metabolism plays a significant role in cellular fatty acid uptake...
  53. Milger K, Herrmann T, Becker C, Gotthardt D, Zickwolf J, Ehehalt R, et al. Cellular uptake of fatty acids driven by the ER-localized acyl-CoA synthetase FATP4. J Cell Sci. 2006;119:4678-88 pubmed
    ..We propose that the enzyme FATP4 drives fatty acid uptake indirectly by esterification. It is not a transporter protein involved in fatty acid translocation at the plasma membrane. ..