Spatiotemporal metabolic mapping reveals diet-independent remodeling of the postnatal mouse brain

Elisa M York; Anne Miller; Sylwia A Stopka; Nathalie Y R Agar; Gary Yellen

doi:10.1038/s44324-025-00098-7

Spatiotemporal metabolic mapping reveals diet-independent remodeling of the postnatal mouse brain

NPJ Metab Health Dis. 2026 Feb 10;4(1):7. doi: 10.1038/s44324-025-00098-7.

Authors

Elisa M York^#^{1

2}, Anne Miller^#^{1

3}, Sylwia A Stopka⁴, Nathalie Y R Agar^{5

6

7}, Gary Yellen⁸

Affiliations

¹ Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
² Molecular Biology, Cellular Biology, and Biochemistry, Brown University, Providence, RI, USA.
³ Center for Pathobiochemistry and Genetics, Medical University of Vienna, Vienna, Austria.
⁴ Department of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA.
⁵ Department of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA. nagar@bwh.harvard.edu.
⁶ Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. nagar@bwh.harvard.edu.
⁷ Department of Cancer Biology, Dana-Farber Cancer Institute; Harvard Medical School, Boston, MA, USA. nagar@bwh.harvard.edu.
⁸ Department of Neurobiology, Harvard Medical School, Boston, MA, USA. gary_yellen@hms.harvard.edu.

^# Contributed equally.

Abstract

Developing cells undergo extensive metabolic adaptations to support growth and differentiation. Here, using spatially resolved mass spectrometry imaging and stable isotope tracing, we systematically investigate metabolic remodeling in mouse brains at postnatal day 14 and day 28, a period coinciding with the transition from a maternal milk diet to solid food. Untargeted metabolomics reveals global shifts in lipid composition, and region-specific remodeling of central energy metabolism, including increased glycolytic intermediates in grey matter-enriched regions and a global decrease in tricarboxylic acid (TCA) cycle metabolites after weaning. Despite these marked changes in metabolite levels, the glucose incorporation rate remains constant across these developmental stages. Notably, weaning mice onto a milk-replacement diet demonstrates that the observed metabolic adaptations are largely diet-independent. Together, our data suggest that postnatal brain metabolic remodeling is an intrinsically programmed feature of maturation providing region-specific metabolic reorganization to support developmental demands.

Abstract

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