A protein has been found that causes fatty food to harm the brain

Fatty food harms more than just the figure: in mice, it reduces levels of the protein PQBP1 in the brain cortex, disrupting connections between neurons and impairing memory. The molecular chain was described by a team led by Hitoshi Okazawa from the Tokyo Institute of Science along with colleagues from Teikyo University. The results of the study were published in the journal Molecular Psychiatry.

The link between high-calorie diets and excess weight and diabetes has been known for a long time. Accumulated data also indicate that they take a toll on the brain — from declining cognitive abilities to an increased risk of neurodegeneration, including Alzheimer's disease. Among the consequences, scientists suspected inflammation in the brain and insulin resistance, but researchers did not know exactly what malfunction occurs in neurons.

PQBP1 controls alternative splicing — the "recutting" of instructions read from DNA, thanks to which a single gene can produce several protein variants. In mice on a high-fat diet, PQBP1 levels in the cortex dropped: the food, through insulin signaling, suppresses the protein PPARγ, which gives the command to read this gene. RNA sequencing showed that in rodents kept on such a diet for one and six weeks, splicing failures occurred in the same synaptic genes as in mice from which this protein had been previously removed from neurons. As a result, the scientists found damaged synapses and failures in memory tests.

The damaged brain, as the authors note, is amenable to repair. Pioglitazone — a drug long prescribed for diabetes — restored levels of this protein, corrected splicing of key genes, and improved memory in the test subjects. Gene therapy also worked: a viral vector delivered a working copy of the needed gene to neurons, and even targeted restoration of individual target genes helped.

"Understanding how diet-related changes in PQBP1 affect splicing and synaptic function opens a new direction in the development of treatments for cognitive impairments," says Okazawa.

All results were obtained in mice, and it is too early to talk about new treatment schemes for the human brain. But the idea itself seems attractive to biologists: an old diabetes drug may one day be able to protect memory in people at risk, and PQBP1-dependent splicing could become a target for new medications. The authors will continue to investigate exactly how food reprograms our brain.