- Metabolic syndrome is associated with memory deficits.
- A new animal study identifies a mechanism that might underpin this effect.
- Researchers show how a high-fat diet affects specific neural circuitry, thereby hindering memory formation.
A mouse study, published earlier this month in the journal
Specifically, the study authors found that metabolic disturbances interfere with the healthy functioning of the hippocampus, which is crucial for memory formation.
If replicated in other studies, the scientists hope that their results might help guide interventions that can reduce this impact on cognitive performance.
Metabolic syndrome is a collection of health conditions that increase the risk of heart disease, stroke, and type 2 diabetes.
If an individual has three or more of the following five conditions, a doctor may diagnose them with metabolic syndrome:
- high levels of abdominal fat
- high levels of triglycerides in the blood
- low levels of HDL, or “good” cholesterol
- high blood sugar levels
- high blood pressure.
Research has shown that metabolic syndrome is associated with cognitive decline and poorer memory.
Additionally, according to the authors of the recent study, “epidemiological studies indicate that individuals with metabolic syndrome face an elevated risk of developing cognitive impairments and neurodegenerative diseases such as Alzheimer’s disease.”
As rates of metabolic syndrome
The brain is a particularly energy-hungry organ. Despite making up just 2% of the body’s weight, it uses around 20% of the energy.
Because of this need for fuel, it is particularly sensitive to dietary intakes. As the authors of the recent study explain, “[a] growing body of evidence suggests that diet plays a crucial role in shaping cognitive function.”
In particular, they call out high-fat diets. Some small
Also, animal research suggests that a high-fat diet may increase the risk of neurodegenerative conditions, like Alzheimer’s disease. Similarly, metabolic syndrome is a risk factor for dementia.
Although links between a high-fat diet and poorer brain health are growing clearer, the precise mechanism by which they impart these issues is unknown. The scientists responsible for the latest study start to bridge this gap.
To explore the relationship between high-fat diets and brain Health, the researchers used a mouse model. They measured neuronal activity within the hippocampus.
In particular, they focused on a part of the hippocampus called the
“The dentate gyrus is a component of a complex circuit in a deep part of the temporal lobe,” Derek Cheng, DO, a board-certified and fellowship-trained neurologist at Stamford Health told Medical News Today.
“It is part of the hippocampal formation and plays many roles, from encoding new memories to possibly processing and differentiating similar memories apart,” Cheng, who was not involved in this research, explained.
The researchers put mice on a high-fat diet for 2 days: 58% fat, 25% carbohydrate, and 17% protein. As expected, cognitive performance was impaired, including memory. Other behaviours, however, remained normal.
The researchers showed that a high-fat diet caused overactivity in so-called cholecystokinin-expressing interneurons (CCK-INs) in the dentate gyrus. This, it seems, caused the memory issues.
Normally, CCK-INs are inhibited by glucose, but because of the high-fat diet, they did not have access to the glucose they needed.
At the same time, there was increased activity of an enzyme important for creating cellular energy (ATP), called glycolytic enzyme pyruvate kinase M2 (PKM2). This enzyme controls the last step of energy production in mitochondria, the powerhouses of the cell.
In further explorations, the scientists found that if they reintroduced glucose or inhibited PKM2 activity, the CCK-INs regained their function and memory deficits were reversed.
The authors wrote that:
“These findings reveal a previously unrecognized mechanism by which dietary metabolic stress disrupts hippocampal function and highlight DG CCK-INs and PKM2 as promising therapeutic targets for preventing cognitive decline associated with metabolic disorders.”
Importantly, the researchers also showed that if glucose was reintroduced and PKM2 inhibited, it prevented memory deficits from occurring in the first place. They also found that periods of fasting reversed the deficits.
This is a mouse study, so it is important to remember that the results may not be applicable to humans. But it does provide intriguing new insights. However, Patric K. Stanton, PhD, a professor of cell biology and anatomy and neurology at New York Medical College was confident that the results may also be relevant to humans.
“It is quite likely that CCK neurons like these, which are present in humans, could underlie a meaningful portion of the cognitive effects, particularly rapid ones produced by a high-fat diet,” explained Stanton, who was not involved in the study.
“We have long known about the association between metabolic syndrome, being overweight, and how unhealthy fatty diets may be associated with dementia,” Cheng told us. “However, it is interesting in this study to see just how quickly — in just a few days — memory formation may be impacted by a poor diet.”
Stanton was also surprised by the speed of the effect: “it was most interesting that cognitive effects were so rapid,” he told us. He further told us he had not expected that “even cognitive effects of long-term high-fat diet consumption could be reversed by manipulations that restored normal inhibition of these neurons.”
These results also suggest that effects of a high-fat diet on the brain begin much earlier than the onset of weight gain and diabetes, explained Stanton.
This new research may guide future studies in humans to better understand how dietary factors can impact brain health, especially regarding metabolic syndrome.
The scientists also theorize that the enzyme PKM2 is worth further investigation. They posit that it could play a role in neurodegenerative conditions more broadly, not just those associated with metabolic dysfunction.
PKM2 is vital for the production of cellular energy, including within the brain.
There is some evidence that neurocognitive conditions — including dementias, mood disorders, and psychosis — may be
Perhaps, in the future, targeting PKM2 will provide new treatment approaches for a range of brain conditions. Only time will tell. For now, the so-called brain energy theory of mental disorders is gaining increasing attention.
Although this is a mouse study and, for this reason, we must wait for more evidence, the results are fascinating and add extra texture and evidence to the already deepening links between nutrition, cellular energy, and brain health.
Importantly, “it highlights the importance of modifiable risk factors such as food choices when it comes to disorders of memory and cognition,” concluded Cheng.
