“Keep eating high-calorie food, and you’ll gain weight easily.”
That much is well known.
Recently, however, researchers have been studying whether overeating and high-fat diets affect not only body weight and blood sugar, but possibly the way the brain works, too .
In September 2026, a research team led by Institute of Science Tokyo announced a new molecular mechanism by which a high-calorie, high-fat diet lowers cognitive function.
The findings were published in the international journal Molecular Psychiatry.
The key point this time is that
a high-calorie diet
↓
a certain protein decreases
↓
abnormalities appear in the “junctions” between nerve cells
↓
cognitive function declines
this sequence was demonstrated concretely in experiments with mice.
Changes After Just One Week of a High-Calorie Diet
In the study, mice were fed either
a normal diet
or
a high-calorie, high-fat diet
and the changes in their brains were examined in detail.
The high-fat diet was given for one week or six weeks.
In both groups, a protein called “PQBP1” had decreased in the nerve cells of the cerebral cortex.
According to the Institute of Science Tokyo announcement, this drop in PQBP1 was not seen in astrocytes or microglia; it occurred specifically in neurons .
In other words, when a high-calorie state affects the brain, it may not simply be that the body’s overall metabolism changes; there may also be changes directly involving the nerve cells themselves .
The Key Player: What Is PQBP1?
PQBP1 is one of the proteins nerve cells need to function properly.
In particular, it is involved in a process called
“RNA splicing.”
That’s the name of the process.
When proteins are made from the information in DNA, the genetic information isn’t used as is; the necessary parts of the RNA are combined to create the final blueprint.
This editing-like process is RNA splicing.
In this study, when PQBP1 decreased because of the high-calorie diet, RNA splicing abnormalities occurred in multiple genes related to synapses .
Among them, the research team focused on molecules such as
CASK
Cacnb1
Cyfip2
Syt1
and others.
These are proteins that play important roles when nerve cells exchange information.
The “Junctions” Between Nerve Cells Had Decreased
Nerve cells in the brain don’t each work alone.
Nerve cells pass information to one another through connection points called
“synapses.”
That’s how they communicate.
You can think of a synapse as“a junction between nerve cells.”That’s the basic idea.
In this study, mice fed a high-calorie diet for one week or six weeks showed, compared with mice on a normal diet, fewer synapses and fewer mature synapses .
Furthermore, the abnormal RNA splicing patterns caused by the high-calorie diet also impaired the release of neurotransmitters from nerve cells.
As a result, the mice also showed a decline in cognitive functions such as memory.
This isn’t simply a matter of the brain “being tired”; changes were occurring in the very structures that support communication between nerve cells.
Why Does a High-Calorie Diet Reduce PQBP1?
The study also investigated the mechanism further upstream.
In the mice fed a high-calorie diet,
weight gain
higher blood sugar
higher insulin
were observed.
The research team then identified the pathway:
a high-calorie state
↓
insulin signaling is activated
↓
the activity of a transcription factor called PPARγ is suppressed
↓
PQBP1 decreases
That’s the pathway they revealed.
PPARγ is an important factor that is also involved in sugar and fat metabolism.
Until now, various explanations, such as inflammation and insulin resistance, have been proposed for cognitive decline caused by high-fat diets.
In addition to these, a major feature of this study is that it revealed
a new pathway inside nerve cells: “PPARγ → PQBP1 → synapses” .
Did a Diabetes Drug Restore Cognitive Function?
The research team also carried out treatment experiments on mice whose cognitive function had declined because of the high-calorie diet.
They used pioglitazone , an existing diabetes medication that enhances the activity of PPARγ.
In the mice fed a high-calorie diet,
long-term memory
short-term memory
synapse structure
and more improved.
Gene therapy that supplemented PQBP1 or the synapse-related molecules downstream of it also improved synapse damage and cognitive decline.
In the future, this could lead to new treatments for cognitive decline associated with obesity and diabetes.
However, this does not mean that
“people who eat high-calorie meals can protect their brains by taking diabetes medication.”
That is not the takeaway.
What was confirmed here is strictly basic research using mice.
Whether the same treatment works in humans will require further research.
What’s interesting about this study is that it showed, at a concrete molecular level, that a high-calorie diet is not just a matter of
body weight
blood sugar
blood lipids
alone, but may affect the very communication between nerve cells .
Of course, these results do not mean that
“eating one hamburger will cause something to go wrong in your brain.”
That’s not what the study shows.
The study used mice, and the conditions differ from human eating habits.
Even so, our daily meals don’t just build our bodies;
they may also be connected to the long-term condition of our brains.
It’s a study that makes us think about that once again.
At La HEAD, we also share a wide range of research related to the condition of the mind and body, including sleep, exercise, stress and diet.
Beyond resting when you’re tired, taking care of your everyday life itself may also be important when it comes to keeping your brain healthy.