A new investigation from UNC School of Medicine, reported in Neuron, reveals how a high‑fat diet reshapes the brain's memory hub, heightening the risk of cognitive decline. The findings point toward early measures that could protect against long‑term memory loss linked to obesity.
Under the direction of Dr. Juan Song, Professor of Pharmacology, and first author Dr. Taylor Landry, researchers examined the hippocampus—an area pivotal for memory. They discovered that a specific class of cells, CCK interneurons, become overactive after just a few days of consuming a high‑fat diet (HFD), owing to impaired glucose uptake in the brain.
This surge in activity disrupts hippocampal function and impairs memory, even though the mice had not yet gained weight or shown signs of diabetes. The diet used in the study, rich in saturated fats like those found in cheeseburgers and fries, is typical of Western junk food.
“We were surprised to see such a rapid effect on a distinct population of neurons,” said Dr. Song of the UNC Neuroscience Center. “The shift in activity happened within days and was enough to compromise memory.”
Key highlights of the research:
- Mouse models were placed on an HFD before behavioral tests began.
- Within four days, CCK interneurons in the hippocampus displayed abnormal hyperactivity.
- These changes precede weight gain or metabolic disease, underscoring the brain’s sensitivity to dietary fats.
The study also identified the enzyme PKM2—as a central regulator of neuronal energy metabolism—as crucial to this process. Restoring glucose availability in the brain reduced the hyperactivity of CCK interneurons and rescued memory performance in mice.
Other interventions, such as intermittent fasting after an HFD period, likewise normalized neuronal activity and improved learning. “Our work shows that what we eat can quickly influence brain health and that early changes, whether through fasting or medication, may guard against obesity‑related memory problems,” remarked Dr. Song.
Future studies aim to see whether similar approaches could be effective in humans and to clarify how high‑fat diets might contribute to neurodegenerative diseases like Alzheimer’s. Researchers will also explore dietary patterns that stabilize brain glucose levels for neuroprotection.