Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Fatty acid oxidation in macrophage polarization

Nature Immunology volume 17, pages 216–217 (2016)Cite this article

Subjects

To the Editor:

Recently, there has been considerable interest in the role of intracellular metabolism as a regulator of the fate and function of cells of the immune system1,2. In macrophages, the classical M1 activation program has been noted to rely on glycolysis, while the M2 program seems to require the induction of fatty acid oxidation (FAO)1,2,3,4. Mitochondria-dependent b-oxidation of long-chain fatty acids requires the carnitine palmitoyltransferase (CPT) system, which consists of one transporter and two mitochondrial membrane enzymes: CPT1 and CPT2 (ref. 5). This system facilitates the transport of long-chain fatty acids into the mitochondrial matrix, where they can be metabolized to produce ATP (Supplementary Fig. 1a). A simple genetic strategy involving loxP-flanked alleles encoding CPT2 (Cpt2fl/fl) has provided the means with which to disrupt FAO within specific mouse cell types6. This is potentially important, because much of the evidence indicating that FAO is required for M2 macrophage polarization has relied on pharmacological approaches, particularly the use of the epoxide etomoxir, which is thought to function as a specific inhibitor of CPT1.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Macrophage FAO is not required for M2 polarization.

References

  1. Odegaard, J.I. & Chawla, A. Immunity 38, 644–654 (2013).

    Article  CAS  Google Scholar 

  2. Pearce, E.L. & Pearce, E.J. Immunity 38, 633–643 (2013).

    Article  CAS  Google Scholar 

  3. Vats, D. et al. Cell Metab. 4, 13–24 (2006).

    Article  CAS  Google Scholar 

  4. Huang, S.C. et al. Nat. Immunol. 15, 846–855 (2014).

    Article  CAS  Google Scholar 

  5. Houten, S.M. & Wanders, R.J. J. Inherit. Metab. Dis. 33, 469–477 (2010).

    Article  CAS  Google Scholar 

  6. Lee, J., Ellis, J.M. & Wolfgang, M.J. Cell Rep. 10, 266–279 (2015).

    Article  CAS  Google Scholar 

  7. Namgaladze, D. & Brune, B. Biochim. Biophys. Acta 1841, 1329–1335 (2014).

    Article  CAS  Google Scholar 

  8. Lee, J., Ellis, J.M. & Wolfgang, M.J. Cell Rep 10, 266–279 (2015).

    Article  CAS  Google Scholar 

  9. Clausen, B.E., Burkhardt, C., Reith, W., Renkawitz, R. & Forster, I. Transgenic Res. 8, 265–277 (1999).

    Article  CAS  Google Scholar 

  10. Samali, A., Cai, J., Zhivotovsky, B., Jones, D.P. & Orrenius, S. EMBO J. 18, 2040–2048 (1999).

    Article  CAS  Google Scholar 

  11. Jenkins, S.J. et al. Science 332, 1284–1288 (2011).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Supported by The US National Institutes of Health (Intramural Funds; and NS072241 for M.J.W.), Fondation Leducq (T.F.) and Japan Society for the Promotion of Science (M.N.).

Author information

Authors and Affiliations

  1. Center for Molecular Medicine, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, USA

    Mitsunori Nomura, Jie Liu, Ilsa I Rovira & Toren Finkel

  2. Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Elsie Gonzalez-Hurtado, Jieun Lee & Michael J Wolfgang

Authors
  1. Mitsunori Nomura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jie Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ilsa I Rovira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elsie Gonzalez-Hurtado
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jieun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michael J Wolfgang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Toren Finkel
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.N. and J.L. performed the experiments; M.N., I.I.R., E.G.-H., J.L., M.J.W. and T.F. analyzed the data; and M.N. and T.F. wrote the manuscript.

Corresponding authors

Correspondence to Michael J Wolfgang or Toren Finkel.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 Transport of long-chain fatty acids into the mitochondrial matrix.

Schematic demonstrating the role of CPT1 located on the outer mitochondrial membrane (OMM) and CPT2 on the inner mitochondrial membrane (IMM) in transporting long chain FAs in the form of Acyl-CoA into the mitochondrial matrix. The drug etomoxir is thought to function as a CPT1 inhibitor.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nomura, M., Liu, J., Rovira, I. et al. Fatty acid oxidation in macrophage polarization. Nat Immunol 17, 216–217 (2016). https://doi.org/10.1038/ni.3366

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ni.3366

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing