For decades, scientists believed the brain relied almost entirely on sugar for fuel. But a new study from Weill Cornell Medicine shows that neurons may also tap into fat to power themselves, especially when they’re working hard.
The research, published in Nature Metabolism, found that brain cells can break down tiny fat droplets stored in their own synapses and convert them into energy. That’s a big shift from the long-standing assumption that “the brain doesn’t burn fat.”
“The process of being able to use the fat is controlled by the electrical activity of the neurons, and I was shocked by this finding,” said senior author Dr. Timothy Ryan. “If the neuron is busy, it drives this consumption. If it’s at rest, the process isn’t happening.”
In other words, the more active the brain, the more it may rely on fat — especially when glucose (its usual fuel) isn’t readily available.
The study also explored a gene called DDHD2, which helps neurons access stored fat. Mice with a faulty version of this gene developed fat build-up in their brains and had trouble breaking it down. Without access to that fuel, brain cells couldn’t generate enough energy to function normally.
The idea that brain cells might turn to fat for fuel isn’t so far-fetched, according to lead author Dr. Mukesh Kumar. He noted that fat serves as an important energy source in other high-demand tissues like muscle, making it plausible that the brain uses it the same way.
To test what happens when this fat-burning process is blocked, researchers used a molecule to stop fatty acids from entering the mitochondria — the part of the cell that generates energy. The mice quickly slipped into a torpor-like state, a form of hibernation, showing just how crucial fat metabolism is to brain activity.
This discovery could reshape how we think about aging brains and neurological diseases. Low glucose levels can occur with age or in conditions like Alzheimer’s and Parkinson’s, and scientists suspect that a neuron’s ability to burn fat might help maintain brain energy under stress.
“By learning more about these molecular details, we hope to ultimately unlock explanations for neurodegeneration, which would give us opportunities for finding ways to protect the brain,” Dr. Ryan said.
The study was supported in part by the National Institutes of Health, the Michael J. Fox Foundation for Parkinson’s Research through the Aligning Science Across Parkinson’s initiative and additional research grants from Rockefeller University and Weill Cornell Medicine.
There’s still much to explore, but one thing is clear: the brain isn’t just a sugar burner. It can — and does — turn to fat when it needs to keep firing.