Skip to main content
Log in

The impact of overexpression and deficiency of fatty acid translocase (FAT)/CD36

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Fatty acid translocase (FAT)/CD36 has been associated with diverse normal and pathologic processes. These include scavenger receptor functions (uptake of apoptotic cells and modified lipid), lipid metabolism and fatty acid transport, adhesion, angiogenesis, modulation of inflammation, transforming growth factor-β activation, atherosclerosis, diabetes and cardiomyopathy. Although CD36 was identified more than 25 years ago, it is only with the advent of recent genetic technology that in vivo evidence has emerged for its physiologic and pathologic relevance. As these in vivo studies are expanded, we will gain further insight into the mechanism(s) by which CD36 transmits a cellular signal, and this will allow the design of specific therapeutics that impact on a particular function of CD36.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Hamilton JA, Johnson RA, Corkey B: Fatty acid transport: The diffusion mechanism in model and biological membranes. J Mol Neurosci 16: 99–108; discussion 151-157, 2001

    Google Scholar 

  2. Hamilton JA, Kamp F: How are free fatty acids transported in membranes? Is it by proteins or by free diffusion through the lipids? Diabetes 48: 2255–2269, 1999

    Google Scholar 

  3. Hamilton JA: Transport of fatty acids across membranes by the diffusion mechanism. Prostagland Leukot Essent Fatty Acids 60: 291–297, 1999

    Google Scholar 

  4. Hamilton JA: Fatty acid transport: Difficult or easy? J Lipid Res 39: 467–481, 1998

    Google Scholar 

  5. Zakim D: Fatty acids enter cells by simple diffusion. Proc Soc Exp Biol Med 212: 5–14, 1996

    Google Scholar 

  6. Abumrad NA, Park JH, Park CR: Permeation of long-chain fatty acid into adipocytes. Kinetics, specificity, and evidence for involvement of a membrane protein. J Biol Chem 259: 8945–8953, 1984

    Google Scholar 

  7. Abumrad NA, Perkins RC, Park JH: Mechanism of long chain fatty acid permeation in the isolated adipocyte. J Biol Chem 256: 9183–9191, 1981

    Google Scholar 

  8. Harmon CM, Abumrad NA: Binding of sulfosuccinimidyl fatty acids to adipocyte membrane proteins: Isolation and amino-terminal sequence of an 88-kD protein implicated in transport of long-chain fatty acids. J Membr Biol 133: 43–49, 1993

    Google Scholar 

  9. Abumrad NA, el-Maghrabi MR, Amri EZ: 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. J Biol Chem 268: 17665–17668, 1993

    Google Scholar 

  10. Stahl A, Gimeno RE, Tartaglia LA: Fatty acid transport proteins: A current view of a growing family. Trends Endocrinol Metab 12: 266–273, 2001

    Google Scholar 

  11. Abumrad N, Coburn C, Ibrahimi A: Membrane proteins implicated in long-chain fatty acid uptake by mammalian cells: CD36, FATP and FABPm. Biochim Biophys Acta 1441: 4–13, 1999

    Google Scholar 

  12. Abumrad NA, el-Maghrabi MR, Amri EZ: 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. J Biol Chem 268: 17665–17668, 1993

    Google Scholar 

  13. Ibrahimi A, Sfeir Z, Magharaie H: Expression of the CD36 homolog (FAT) in fibroblast cells: Effects on fatty acid transport. Proc Natl Acad Sci USA 93: 2646–2651, 1996

    Google Scholar 

  14. Ibrahimi A, Bonen A, Blinn WD: Muscle-specific overexpression of FAT/CD36 enhances fatty acid oxidation by contracting muscle, reduces plasma triglycerides and fatty acids, and increases plasma glucose and insulin. J Biol Chem 274: 26761–26766, 1999

    Google Scholar 

  15. Van Nieuwenhoven FA, Verstijnen CP, Abumrad NA: Putative membrane fatty acid translocase and cytoplasmic fatty acid-binding protein are co-expressed in rat heart and skeletal muscles. Biochem Biophys Res Commun 207: 747–752, 1995

    Google Scholar 

  16. Watanabe K, Ohta Y, Toba K: Myocardial CD36 expression and fatty acid accumulation in patients with type I and II CD36 deficiency. Ann Nucl Med 12: 261–266, 1998

    Google Scholar 

  17. Bonen A, Luiken JJ, Liu S: Palmitate transport and fatty acid transporters in red and white muscles. Am J Physiol 275: E471–478, 1998

    Google Scholar 

  18. Bonen A, Dyck DJ, Ibrahimi A: Muscle contractile activity increases fatty acid metabolism and transport and FAT/CD36. Am J Physiol 276: E642–649, 1999

    Google Scholar 

  19. Coburn CT, Knapp FF Jr, Febbraio M: Defective uptake and utilization of long chain fatty acids in muscle and adipose tissues of CD36 knockout mice. J Biol Chem 275: 32523–32529, 2000

    Google Scholar 

  20. Fukuchi K, Nozaki S, Yoshizumi T: Enhanced myocardial glucose use in patients with a deficiency in long-chain fatty acid transport (CD36 deficiency). J Nucl Med 40: 239–243, 1999

    Google Scholar 

  21. Hajri T, Ibrahimi A, Coburn CT: Defective fatty acid uptake in the spontaneously hypertensive rat is a primary determinant of altered glucose metabolism, hyperinsulinemia and myocardial hypertrophy. J Biol Chem 25: 25, 2001

    Google Scholar 

  22. Nozaki S, Tanaka T, Yamashita S: CD36 mediates long-chain fatty acid transport in human myocardium: Complete myocardial accumulation defect of radiolabeled long-chain fatty acid analog in subjects with CD36 deficiency. Mol Cell Biochem 192: 129–135, 1999

    Google Scholar 

  23. Pravenec M, Landa V, Zidek V: Transgenic rescue of defective Cd36 ameliorates insulin resistance in spontaneously hypertensive rats. Nat Genet 27: 156–158, 2001

    Google Scholar 

  24. Collison M, Glazier AM, Graham D: Cd36 and molecular mechanisms of insulin resistance in the stroke-prone spontaneously hypertensive rat. Diabetes 49: 2222–2226, 2000

    Google Scholar 

  25. Febbraio M, Abumrad NA, Hajjar DP: A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism. J Biol Chem 274: 19055–19062, 1999

    Google Scholar 

  26. Watanabe K, Toba K, Ogawa Y: Hypertrophic cardiomyopathy with type I CD36 deficiency. Jpn Circ J 62: 541–542, 1998

    Google Scholar 

  27. Tanaka T, Sohmiya K, Kawamura K: Is CD36 deficiency an etiology of hereditary hypertrophic cardiomyopathy? J Mol Cell Cardiol 29: 121–127, 1997

    Google Scholar 

  28. Watanabe K, Ohta Y, Toba K: Myocardial CD36 expression and fatty acid accumulation in patients with type I and II CD36 deficiency. Ann Nucl Med 12: 261–266, 1998

    Google Scholar 

  29. Gotoda T, Iizuka Y, Yamada N: Complex connection between CD36 and atherosclerosis, lipid metabolism, and insulin resistance syndromes. Curr Atheroscler Rep 2: 453–454, 2000

    Google Scholar 

  30. Miyaoka K, Kuwasako T, Hirano K: CD36 deficiency associated with insulin resistance. Lancet 357: 686–687, 2001

    Google Scholar 

  31. Yanai H, Chiba H, Morimoto M: Type I CD36 deficiency in humans is not associated with insulin resistance syndrome. Thromb Haemost 83: 786., 2000

    Google Scholar 

  32. Gruarin P, Thorne RF, Dorahy DJ: CD36 is a ditopic glycoprotein with the N-terminal domain implicated in intracellular transport. Biochem Biophys Res Commun 275: 446–454, 2000

    Google Scholar 

  33. Oquendo P, Hundt E, Lawler J: CD36 directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes. Cell 58: 95–101, 1989

    Google Scholar 

  34. Tao N, Wagner SJ, Lublin DM: CD36 is palmitoylated on both Nand C-terminal cytoplasmic tails. J Biol Chem 271: 22315–22320, 1996

    Google Scholar 

  35. Greenwalt DE, Lipsky RH, Ockenhouse CF: Membrane glycoprotein CD36: A review of its roles in adherence, signal transduction, and transfusion medicine. Blood 80: 1105–1115, 1992

    Google Scholar 

  36. Greenwalt DE, Mather IH: Characterization of an apically derived epithelial membrane glycoprotein from bovine milk, which is expressed in capillary endothelia in diverse tissues. J Cell Biol 100: 397–408, 1985

    Google Scholar 

  37. Swerlick RA, Lee KH, Wick TM: Human dermal microvascular endothelial but not human umbilical vein endothelial cells express CD36 in vivo and in vitro. J Immunol 148: 78–83, 1992

    Google Scholar 

  38. Ryeom SW, Sparrow JR, Silverstein RL: CD36 participates in the phagocytosis of rod outer segments by retinal pigment epithelium. J Cell Sci 109: 387–395, 1996

    Google Scholar 

  39. Endemann G, Stanton LW, Madden KS, et al.: CD36 is a receptor for oxidized low density lipoprotein. J Biol Chem 268: 11811–11816, 1993

    Google Scholar 

  40. Ryeom SW, Silverstein RL, Scotto A: Binding of anionic phospholipids to retinal pigment epithelium may be mediated by the scavenger receptor CD36. J Biol Chem 271: 20536–20539, 1996

    Google Scholar 

  41. Silverstein RL, Asch AS, Nachman RL: Glycoprotein IV mediates thrombospondin-dependent platelet-monocyte and platelet-U937 cell adhesion. J Clin Invest 84: 546–552, 1989

    Google Scholar 

  42. Lisanti MP, Scherer PE, Vidugiriene J: Characterization of caveolin-rich membrane domains isolated from an endothelial-rich source: Implications for human disease. J Cell Biol 126: 111–126, 19942

    Google Scholar 

  43. Dorahy DJ, Lincz LF, Meldrum CJ: Biochemical isolation of a membrane microdomain from resting platelets highly enriched in the plasma membrane glycoprotein CD36. Biochem J 319: 67–72, 1996

    Google Scholar 

  44. Lee H, Woodman SE, Engelman JA: Palmitoylation of caveolin-1 at a single site (Cys-156) controls its coupling to the c-Src tyrosine kinase. J Biol Chem 12: 12, 2001

    Google Scholar 

  45. Savill J, Hogg N, Ren Y: Thrombospondin cooperates with CD36 and the vitronectin receptor in macrophage recognition of neutrophils undergoing apoptosis. J Clin Invest 90: 1513–1522, 1992

    Google Scholar 

  46. Dawson DW, Pearce SF, Zhong R: CD36 mediates the in vitro inhibitory effects of thrombospondin-1 on endothelial cells. J Cell Biol 138: 707–717, 1997

    Google Scholar 

  47. Jimenez B, Volpert OV, Crawford SE: Signals leading to apoptosisdependent inhibition of neovascularization by thrombospondin-1. Nat Med 6: 41–48, 2000

    Google Scholar 

  48. Sfeir Z, Ibrahimi A, Amri E: Regulation of FAT/CD36 gene expression: Further evidence in support of a role of the protein in fatty acid binding/transport. Prostaglandins Leukot Essent Fatty Acids 57: 17–21, 1997

    Google Scholar 

  49. Luiken JJ, van Nieuwenhoven FA, America G: Uptake and metabolism of palmitate by isolated cardiac myocytes from adult rats: Involvement of sarcolemmal proteins. J Lipid Res 38: 745–758, 1997

    Google Scholar 

  50. Luiken JJ, Willems J, van der Vusse GJ: Electrostimulation enhances FAT/CD36-mediated long-chain fatty acid uptake by isolated rat cardiac myocytes. Am J Physiol Endocrinol Metab 281: E704–712, 2001

    Google Scholar 

  51. Binas B, Danneberg H, McWhir J: Requirement for the heart-type fatty acid binding protein in cardiac fatty acid utilization. Faseb J 13: 805–812, 1999

    Google Scholar 

  52. Glatz JF, van Nieuwenhoven FA, Luiken JJ: Role of membrane-associated and cytoplasmic fatty acid-binding proteins in cellular fatty acid metabolism. Prostaglandins Leukot Essent Fatty Acids 57: 373–378, 1997

    Google Scholar 

  53. Aitman TJ, Glazier AM, Wallace CA: Identification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats. Nat Genet 21: 76–83, 1999

    Google Scholar 

  54. Pravenec M, Landa V, Zidek V: Transgenic rescue of defective Cd36 ameliorates insulin resistance in spontaneously hypertensive rats. Nat Genet 27: 156–158, 2001

    Google Scholar 

  55. Knapp FF, Jr., Kropp J, Franken PR: Pharmacokinetics of radioiodinated fatty acid myocardial imaging agents in animal models and human studies. Quart J Nucl Med 40: 252–269, 1996

    Google Scholar 

  56. Li AC, Brown KK, Silvestre MJ: Peroxisome proliferator-activated receptor gamma ligands inhibit development of atherosclerosis in LDL receptor-deficient mice. J Clin Invest 106: 523–531, 2000

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Febbraio, M., Guy, E., Coburn, C. et al. The impact of overexpression and deficiency of fatty acid translocase (FAT)/CD36. Mol Cell Biochem 239, 193–197 (2002). https://doi.org/10.1023/A:1020515210972

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1020515210972

Navigation