Chapel Hill, N.C. - Diet impacts the brain a lot more than we think.
A new study from UNC School of Medicine researchers, published this week in Neuron, reveals a unique look at how junk food rewires the brain's memory hub - leading to risk of cognitive dysfunction. This new research opens the door to early interventions that can prevent even long-term memory loss associated with obesity.
Led by UNC School of Medicine's Juan Song, PhD, principal investigator, professor of pharmacology, and Taylor Landry, PhD, first author, Department of Pharmacology, researchers found that a special group of brain cells in the hippocampus, called CCK interneurons, become overly active after eating a high-fat diet (HFD), due to an impaired ability of the brain to receive glucose (sugar). This overactivity disrupts how the hippocampus processes memory, even after just a few days of high fat diet. This type of diet resembles typical Western-style junk food rich in saturated fat-like cheeseburgers and fries. The discovery also showed that a protein called PKM2, which controls how brain cells use energy, plays a key role in this problem.
"We knew that diet and metabolism could affect brain health, but we didn't expect to find such a specific and vulnerable group of brain cells, CCK interneurons in the hippocampus, that were directly disrupted by short-term high-fat diet exposure," Song said, who is a member of the UNC Neuroscience Center. "What surprised us most was how quickly these cells changed their activity in response to reduced glucose availability, and how this shift alone was enough to impair memory."
Brain Health Study Summary
- Mouse models were placed on high-fat diet resembling fatty junk food before starting behavioral testing.
- Within 4 days of eating high-fat diet, results showed CCK interneurons in the brain's memory hub became abnormally active.
- Results suggest fatty junk foods can affect the brain almost immediately, well before the onset of weight gain or diabetes.
Research findings also highlight how sensitive memory circuits are to diet, underscoring the importance of nutrition in maintaining brain health. A high-fat diet, rich in saturated fats, could possibly lead to an elevated risk of developing neurodegenerative diseases, like dementia and Alzheimer's, according to the study.
The research also shows that restoring brain glucose levels actually calmed down overactive neurons and fixed memory problems in mice. The study found interventions like dietary modifications or pharmacological approaches may be effective in preserving brain health for obesity-related neurodegeneration. Notably, researchers discovered that dietary interventions like intermittent fasting periods following a high-fat diet were sufficient to normalize CCK interneurons and improve memory function.
"This work highlights how what we eat can rapidly affect brain health and how early interventions, whether through fasting or medicine, could protect memory and lower the risk of long-term cognitive problems linked to obesity and metabolic disorders," said Song. "In the long run, such strategies could help reduce the growing burden of dementia and Alzheimer's linked to metabolic disorders, offering more holistic care that addresses both body and brain."
This research is ongoing to further understand how these glucose-sensitive neurons disrupt brain rhythms that support memory. Researchers plan to test whether these targeted therapies could be translated into humans and how a high-fat diet could be a factor in Alzheimer's disease. Lifestyle-based interventions will also be explored, such as dietary patterns that stabilize brain glucose, to see if they offer protective benefits.
