Study Discovers How Calorie-Rich Diets May Disrupt Brain Function and Memory - Video

Could eating a high-fat, calorie-rich diet silently damage brain cells and impair memory? A new study suggests that high-fat diets may disrupt important molecular processes in the brain, affecting communication between neurons and contributing to cognitive impairment.

Published in Molecular Psychiatry, the study conducted by researchers at the Institute of Science Tokyo, Japan, investigated how high-fat diets influence brain function and the molecular mechanisms responsible for diet-related cognitive decline.

High-calorie diets are widely associated with obesity, diabetes and metabolic disorders. Growing evidence also suggests that excessive dietary fat consumption may negatively affect cognitive performance and increase vulnerability to neurodegenerative conditions.

To investigate these effects, researchers fed mice a high-fat diet and examined changes in brain proteins, gene regulation and neuronal communication.

The findings revealed that high-fat feeding reduced levels of PQBP1, a protein involved in alternative RNA splicing, in the cerebral cortex, a brain region responsible for several cognitive functions.

Alternative RNA splicing allows individual genes to produce different RNA transcripts and proteins essential for normal cellular functioning.

Researchers discovered that reduced PQBP1 levels disrupted the processing of genes involved in synaptic function, resulting in abnormalities in neuronal connections and impaired cognitive performance.

Further analysis identified altered PPARγ signalling as a possible mechanism contributing to reduced PQBP1 expression.

Interestingly, researchers found that treatment with pioglitazone, a diabetes medication that activates PPARγ, restored PQBP1 levels, corrected abnormal RNA splicing and improved synaptic function and cognitive outcomes in mice.

Gene therapy designed to restore PQBP1 also reversed several neuronal abnormalities and cognitive deficits.

However, researchers cautioned that these findings were obtained from animal experiments and require further investigation before their relevance to human cognitive health can be established.

REFERENCE: Huang, Y., et al. (2026). PQBP1-dependent alternative RNA splicing underlies high calorie diet-induced cognitive impairment. Molecular Psychiatry. DOI: 10.1038/s41380-026-03868-x