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Fatty acid oxidation in macrophage polarization

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

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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.

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

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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.).

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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
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  2. Jie Liu
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  3. Ilsa I Rovira
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  4. Elsie Gonzalez-Hurtado
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  5. Jieun Lee
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  6. Michael J Wolfgang
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  7. Toren Finkel
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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.

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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.

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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

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