Brain lipids are organized into zones — and reorganized during pregnancy

Macosko, Evan

doi:10.1038/d41586-026-02772-2

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23 September 2026

Brain lipids are organized into zones — and reorganized during pregnancy

A map of fats across the whole mouse brain reveals a spatial architecture that differs from that seen in gene-expression and protein atlases.

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Evan Macosko⁰

Evan Macosko
1. Evan Macosko is in the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
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When the pioneering German–British neurochemist Johann Thudichum generated the first catalogue of brain lipids more than a century ago, one molecular fraction baffled him so much that he named it sphingosine, after the enigmatic ancient Sphinx¹. A century and a half later, the brain’s fats have retained much of that mystery. Comprising half of its dry weight, lipids are perhaps the brain’s most defining compositional feature. Their most famous role is forming the insulating myelin wrapping that enables efficient electrical conduction along neuronal projections called axons. But beyond this, a broader conceptual understanding of brain lipids is still in its infancy. How the vast diversity of brain lipids is spatially organized, and why the brain requires such immense biochemical variety, remains a big puzzle — one that Bassini et al.² begin to address in their paper in Nature.

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Nature 658, 43-44 (2026)

doi: https://doi.org/10.1038/d41586-026-02772-2

References

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The author declares no competing interests.

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[1] Thudichum, J. L. W. A Treatise on the Chemical Constitution of the Brain (Bailliere Tindall, 1884).
Google Scholar

[2] Bassini, L. F. et al. Nature 658, 205–217 (2026).
Article Google Scholar

[3] Langlieb, J. et al. Nature 624, 333–342 (2023).
Article PubMed Google Scholar

[4] Yao, Z. et al. Nature 624, 317–332 (2023).
Article PubMed Google Scholar

[5] Sjöstedt, E. et al. Science 367, eaay5947 (2020).
Article PubMed Google Scholar

[6] Oh, S. W. et al. Nature 508, 207–214 (2014).
Article PubMed Google Scholar

[7] Pritschet, L. et al. Nature Neurosci. 27, 2253–2260 (2024).
Article PubMed Google Scholar

[8] da Silva, R. R., Dorrestein, P. C. & Quinn, R. A. Proc. Natl Acad. Sci. USA 112, 12549–12550 (2015).
Article PubMed Google Scholar

[9] Hoffmann, M. A. et al. Nature Biotechnol. 40, 411–421 (2022).
Article PubMed Google Scholar

[10] Stravs, M. A., Dührkop, K., Böcker, S. & Zamboni, N. Nature Methods 19, 865–870 (2022).
Article PubMed Google Scholar

[11] Skinnider, M. A., Stacey, R. G., Wishart, D. S. & Foster, L. J. Nature Mach. Intell. 3, 759–770 (2021).
Article Google Scholar

[12] Vaughen, J. P., Theisen, E. & Clandinin, T. R. Curr. Opin. Neurobiol. 80, 102702 (2023).
Article PubMed Google Scholar

[13] Vaughen, J. P. et al. Neuron 110, 3186–3205 (2022).
Article PubMed Google Scholar

[14] Hansen, S. B., Tao, X. & MacKinnon, R. Nature 477, 495–498 (2011).
Article PubMed Google Scholar

[15] Ioannou, M. S. et al. Cell 177, 1522–1535 (2019).
Article PubMed Google Scholar

[16] Frank, J. A., Franquelim, H. G., Schwille, P. & Trauner, D. J. Am. Chem. Soc. 138, 12981–12986 (2016).
Article PubMed Google Scholar

[17] Hartrampf, N. et al. Biophys. J. 122, 2325–2341 (2023).
Article PubMed Google Scholar

[18] Mukhopadhyay, T. K., Morstein, J. & Trauner, D. Curr. Opin. Pharmacol. 63, 102202 (2022).
Article PubMed Google Scholar

[19] Idevall-Hagren, O., Dickson, E. J., Hille, B., Toomre, D. K. & De Camilli, P. Proc. Natl Acad. Sci. USA 109, E2316–E2323 (2012).
Article PubMed Google Scholar

[20] Tei, R., Li, X.-L., Luan, L. & Baskin, J. M. Nature Chem. Biol. 22, 728–739 (2026).
Article PubMed Google Scholar

Brain lipids are organized into zones — and reorganized during pregnancy

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