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Study · Nature · 2025Conflicts declared

High fructose and brain development in young mice

Wang Z, Lipshutz A, Martínez de la Torre C, et al · Free full text

What it found

In young mice, a high fructose diet reduced the brain's immune cells' ability to clear dying neurons, and these mice later showed anxiety-like behaviour.

The effects were reversed when the fructose transporter GLUT5 was removed.

What they found

Animal and lab studies

Microglia in newborn mice

Newborn mice exposed to high fructose had fewer microglia and more uncleared dying cells in the prefrontal cortex. Their microglia also had a shape linked to being less active.

Phagocytosis reduced

Microglia from fructose-exposed newborns swallowed less neuronal debris, measured by a marker for phagocytosis. The effect was seen whether fructose was given during pregnancy, nursing, or directly to the newborn.

GLUT5 required

Removing the fructose transporter GLUT5 completely reversed the microglia problems in newborn mice. The same reversal happened when GLUT5 was removed only from myeloid cells, which include microglia.

Direct effect on microglia

In lab tests, high fructose directly reduced the ability of mouse and human microglia to swallow synapses and dying neurons. This effect was reversed in microglia lacking GLUT5.

Metabolism changes

High fructose made microglia take in and break down more fructose, producing more fructose 6-phosphate and shifting their metabolism. This was linked to more of the enzyme hexokinase 2 moving to mitochondria and less ATP, a cellular energy molecule.

Anxiety-like behaviour

Adolescent mice exposed to high fructose early in life showed poorer recognition memory and weaker fear extinction, a sign of anxiety-like behaviour. These problems were reversed in mice lacking GLUT5.

What the authors conclude

“Our findings provide a mechanistic explanation for the epidemiological observation that high-fructose exposure during early life is associated with increased prevalence of adolescent anxiety disorders.”
Wang Z, Lipshutz A, Martínez de la Torre C, et al, 2025

Also in their conclusions

  • They say their work provides a mechanistic explanation for the link between early life high fructose exposure and increased anxiety disorder prevalence in adolescents.
  • They note that high fructose consumption itself likely does not cause mood or anxiety disorders, but may act as a first hit that requires a later trauma to trigger a disorder.
  • They call for more research on how fructose and GLUT5 affect microglia in health and disease, especially given the rise in mood and anxiety disorders.

How it was done

The authors wanted to understand whether the link between high fructose consumption during pregnancy or adolescence and disrupted brain development is caused by fructose acting directly on cells in the brain.

They fed pregnant mice a diet with 15% of calories from fructose, or gave newborn mice fructose directly, and studied their offspring's brain immune cells. They also tested the effects of fructose on mouse and human microglia grown in the lab, and ran behaviour tests on adolescent mice.

What it can’t tell you

  • These are animal and lab studies. They cannot show whether the same effects happen in people.
  • The study cannot prove that high fructose consumption directly causes anxiety disorders in humans.
  • The long-term effects of early life fructose exposure on human brain development remain unknown.

The paper

Title
Early life high fructose impairs microglial phagocytosis and neurodevelopment
Type
Study
Evidence
Animals and lab studies
Summarised from
Full text
Cite
Wang Z, Lipshutz A, Martínez de la Torre C, et al (2025). Early life high fructose impairs microglial phagocytosis and neurodevelopment. Nature. doi:10.1038/s41586-025-09098-5Free full textPubMed 40500435DOI

Summary written 26 Sep 2026. Check it against the paper before it changes what you eat. How we summarise papers · Report an error