Skip to main content
Log in

Role of CD36 in membrane transport and utilization of long-chain fatty acids by different tissues

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

The transmembrane glycoprotein CD36 has been identified in isolated cell studies as a putative transporter of long-chain fatty acids. To examine the physiological role of CD36, we studied FA uptake and metabolism by tissues of CD36 null mice after injection with two fatty acid analogs. Compared to controls, uptake was substantially reduced (50–80%) in heart, skeletal muscle, and adipose tissues of null mice. The reduction in uptake was associated with a large decrease in fatty acid incorporation into triglycerides, which could be accounted for by an accumulation of diacylglycerides. Thus CD36 facilitates a major fraction of fatty acid uptake by myocardial, skeletal muscle, and adipose tissues, where it is highly expressed. Its role in other tissues where its expression is low and cell-specific could not be determined in these studies.

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.

Institutional subscriptions

Similar content being viewed by others

References

  • Abumrad N. A., Park J. H., and Park C. R. (1984) Permeation of long-chain fatty acid into adipocytes. Kinetics, specificity, and evidence for involvement of a membrane protein. J. Biol. Chem. 259, 8945–8953.

    PubMed  CAS  Google Scholar 

  • Abumrad N. A., el-Maghrabi M. R., Amri E. Z., Lopez E., and Grimaldi P. A. (1993) 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, 17,665–17,668.

    CAS  Google Scholar 

  • Abumrad N., Harmon C., and Ibrahimi A. (1998) Membrane transport of long-chain fatty acids: evidence for a facilitated process. J. Lipid Res. 39, 2309–2318.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Aitman T. J., Glazier A. M., Wallace C. A., Cooper L. D., Norsworthy P. J., Wahid F. N., et al. (1999) Identification of CD36 (FAT) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats. Nature Genet. 21, 76–83.

    Article  PubMed  CAS  Google Scholar 

  • Amri E. Z., Bonino F., Ailhaud G., Abumrad N. A., and Grimaldi P. A. (1995) Cloning of a protein that mediates transcriptional effects of fatty acids in preadipocytes. Homology to peroxisome proliferator-activated receptors. J. Biol. Chem. 270, 2367–2371.

    Article  PubMed  CAS  Google Scholar 

  • Auestad N., Korsak R. A., Morrow J. W., and Edmond J. (1991) Fatty acid oxidation and ketogenesis by astrocytes in primary culture. J. Neurochem. 56, 1376–1386.

    Article  PubMed  CAS  Google Scholar 

  • Balendiran G. K., Schnutgen F., Scapin G., Borchers T., Xhong N., Lim K., et al. (2000) Crystal structure and thermodynamic analysis of human brain fatty acid binding protein. J. Biol. Chem., in press.

  • Bonen A., Dyck D. J., Ibrahimi A., and Abumrad N. A. (1999) Muscle contractile activity increases fatty acid metabolism and transport and FAT/CD36. Am. J. Physiol. 276, E642-E649.

    PubMed  CAS  Google Scholar 

  • Bonen A., Luiken J. J., Arumugam Y., Glatz J. F., and Tandon N. N. (2000) Acute regulation of fatty acid uptake involves the cellular redistribution of fatty acid translocase. J. Biol. Chem. 275, 14,501–14,508.

    Article  CAS  Google Scholar 

  • Coburn C. T., Knapp Jr. F. F., Febbraio M., Beets A. L., Silverstein R. L., and Abumrad N. A. (2000) Defective uptake and utilization of long-chain fatty acids in muscle and adipose tissues of CD36 knockout mice. J. Biol. Chem., 275, 32,523–32,529.

    Article  CAS  Google Scholar 

  • Febbraio M., Abumrad N. A., Hajjar D. P., Sharma K., Cheng W., Pearce S. F., and Silverstein R. L. (1999) A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism. J. Biol. Chem. 274, 19,055–19,062.

    Article  CAS  Google Scholar 

  • Greenwalt D. E., Lipsky R. H., Ockenhouse C. F., Ikeda H., Tandon N. N., and Jamieson G. A. (1992) Membrane glycoprotein CD36: a review of its roles in adherence, signal transduction, and transfusion medicine. Blood 80, 1105–1115.

    PubMed  CAS  Google Scholar 

  • Harmon C. M. and Abumrad N. A. (1993) 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.

    PubMed  CAS  Google Scholar 

  • Heuckeroth R. O., Birkenmeier E. H., Levin M. S., and Gordon J. I. (1987) Analysis of the tissue-specific expression, developmental regulation, and linkage relationships of a rodent gene encoding heart fatty acid binding protein. J. Biol. Chem. 262, 9709–9717.

    PubMed  CAS  Google Scholar 

  • Hirsch D., Stahl A., and Lodish H. F. (1998) A family of fatty acid transporters conserved from mycobacterium to man. Proc. Natl. Acad. Sci. USA 95, 8625–8629.

    Article  PubMed  CAS  Google Scholar 

  • Hwang E. H., Taki J., Yasue S., Fujimoto M., Taniguchi M., Matsunari I., et al. (1998) Absent myocardial iodine-123-BMIPP uptake and platelet/monocyte CD36 deficiency. J. Nucleic Med. 39, 1681–1684.

    CAS  Google Scholar 

  • Ibrahimi A., Sfeir Z., Magharaie H., Amri E. Z., Grimaldi P., and Abumrad N. A. (1996) Expression of the CD36 homolog (FAT) in fibroblast cells: effects on fatty acid transport. Proc. Natl. Acad. Sci. USA 93, 2646–2651.

    Article  PubMed  CAS  Google Scholar 

  • Ibrahimi A., Bonen A., Blinn W. D., Hajri T., Li X., Zhong K., Cameron R., and Abumrad N. A. (1999) 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, 26,761–26,766.

    Article  CAS  Google Scholar 

  • Knapp Jr. F. F., Ambrose K. R., and Goodman M. M. (1986) New radioiodinated methyl-branched fatty acids for cardiac studies. Eur. J. Nucleic Med. 12(Suppl.), S39-S44.

    Article  CAS  Google Scholar 

  • Poirier H., Degrace P., Niot I., Bernard A., and Besnard P. (1996) Localization and regulation of the putative membrane fatty-acid transporter (FAT) in the small intestine. Comparison with fatty acid-binding proteins (FABP). Eur. J. Biochem. 238, 368–373.

    Article  PubMed  CAS  Google Scholar 

  • Pravenec M., Zidek V., Simakova M., Kren V., Krenova D., Horky K., et al. (1999) Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension. J. Clin. Invest. 103, 1651–1657.

    Article  PubMed  CAS  Google Scholar 

  • Richieri G. V. and Kleinfeld A. M. (1995) Unbound free fatty acid levels in human serum. J. Lipid Res. 36, 229–240.

    PubMed  CAS  Google Scholar 

  • Richieri G. V., Ogata R. T., Zimmerman A. W., Veerkamp J. H., and Kleinfeld A. M. (2000) Fatty acid binding proteins from different tissues show distinct patterns of fatty acid interactions. Biochemistry 39, 7197–7204.

    Article  PubMed  CAS  Google Scholar 

  • Schaffer J. E. and Lodish H. F. (1994) Expression cloning and characterization of a novel adipocyte long chain fatty acid transport protein. Cell 79, 427–436.

    Article  PubMed  CAS  Google Scholar 

  • Spitsberg V. L., Matitashvili E., and Gorewit R. C. (1995) Association and coexpression of fatty-acid-binding protein and glycoprotein CD36 in the bovine mammary gland. Eur. J. Biochem. 230, 872–878.

    Article  PubMed  CAS  Google Scholar 

  • Stump D. D., Zhou S. L., and Berk P. D. (1993) Comparison of plasma membrane FABP and mitochondrial isoform of aspartate aminotransferase from rat liver. Am. J. Physiol. 265, G894-G902.

    PubMed  CAS  Google Scholar 

  • Tontonoz P. and Nagy L. (1999) Regulation of macrophage gene expression by peroxisome-proliferator-activated receptor gamma: implications for cardiovascular disease. Curr. Opin. Lipidol. 10, 485–490.

    Article  PubMed  CAS  Google Scholar 

  • van der Lee K. A., Vork M. M., De Vries J. E., Willemsen, P. H. Glatz J. F., Reneman R. S., et al. (2000) Long-chain fatty acid-induced changes in gene expression in neonatal cardiac myocytes. J. Lipid Res. 41, 41–47.

    PubMed  Google Scholar 

  • Watanabe K., Ohta Y., Toba K., Ogawa Y., Hanawa H., Hirokawa Y., et al. (1998) Myocardial CD36 expression and fatty acid accumulation in patients with type I and II CD36 deficiency. Ann. Nucleic Med. 12, 261–266.

    Article  CAS  Google Scholar 

  • Yoshizumi T., Nozaki S., Fukuchi K., Yamasaki K., Fukuchi T., Maruyama T., et al. (2000) Pharmacokinetics and metabolism of 123I-BMIPP fatty acid analog in healthy and CD36-deficient subjects [In Process Citation]. J. Nucleic Med. 41, 1134–1138.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nada A. Abumrad.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Coburn, C.T., Hajri, T., Ibrahimi, A. et al. Role of CD36 in membrane transport and utilization of long-chain fatty acids by different tissues. J Mol Neurosci 16, 117–121 (2001). https://doi.org/10.1385/JMN:16:2-3:117

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/JMN:16:2-3:117

Index Entries

Navigation