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

TL;DR

The study shows that the developing mouse brain undergoes metabolic changes during weaning, which are largely driven by internal programming rather than diet.

Contribution

The study reveals that postnatal brain metabolic remodeling is intrinsically programmed and not primarily diet-dependent.

Findings

Untargeted metabolomics identified global shifts in lipid composition and region-specific changes in energy metabolism.

Glucose incorporation rates remained constant despite changes in metabolite levels after weaning.

Metabolic adaptations observed were largely independent of diet, as shown by weaning onto a milk-replacement diet.

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.

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