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 NeuronTrusted Source, zeroes in on a neurological mechanism that may help explain why memory deficits occur in response to long-term high-fat diets.
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, high-fat diets, and memory
Metabolic syndrome is a group 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 continue to riseTrusted Source in the United States, understanding precisely how they influence brain health is an important topic of research.
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 studiesTrusted Source have concluded that a high-fat diet is linked to poorer cognitive performance, even after just a short time. It seems that the hippocampus — a brain region vital for memory formation — might be particularly susceptible Trusted Source to the issues caused by a high-fat diet.
Also, animal research suggests that a high-fat diet may increase the risk of neurodegenerative conditions, such as Alzheimer’s disease. Likewise, 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 begin to bridge this gap.
What happens in the brain?
To explore the relationship between high-fat diets and brain health, the researchers used a mouse model. They measure neuronal activity within the hippocampus.
In particular, they focused on a part of the hippocampus called the dentate gyrusTrusted Source, a region within the hippocampus that is considered particularly important for forming new memories.
“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 possible 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 sh
