For decades, scientists believed that the brain’s nerve cells, or neurons, relied only on sugar for energy.
But new research from the University of Queensland has revealed a surprising alternative fuel source—fats.
This breakthrough could open the door to new treatments for devastating brain disorders.
The study, published in Nature Metabolism, was led by Dr. Merja Joensuu from UQ’s Australian Institute for Bioengineering and Nanotechnology.
Working with Ph.D. candidate Nyakuoy Yak and Dr. Saber Abd Elkader from UQ’s Queensland Brain Institute, the team discovered that neurons use small fat molecules, known as saturated free fatty acids, to power the signals that allow us to think, move, and feel.
“This challenges the long-held belief that glucose alone fuels brain activity,” Dr. Joensuu explained.
“Our findings show fats are a crucial part of how neurons produce energy, and this insight could help us repair and restore brain function when it fails.”
The research focused on a rare genetic condition called hereditary spastic paraplegia 54 (HSP54), which is triggered by faults in a gene called DDHD2.
The gene is important for keeping the brain’s fat supply in balance. When DDHD2 stops working properly, neurons cannot access the fat fuel they need, which leads to problems with communication between brain cells and, eventually, serious neurological symptoms.
The team’s experiments showed that neurons normally produce and use their own saturated fatty acids to keep firing signals.
In models of HSP54, however, this process was disrupted. To test possible treatments, the researchers tried boosting sugar intake, but this made no difference. When they instead supplemented with activated fatty acids, energy production was restored, and the neurons returned to normal function.
“This was a huge shift in our understanding,” said Dr. Joensuu. “It showed that neurons can fuel themselves with fatty acids, and if this pathway breaks down, it can be repaired with fatty acid supplements.”
The findings not only offer hope for people with HSP54 but may also be relevant to a range of metabolic brain disorders.
Many conditions, including Alzheimer’s disease, involve changes in the brain’s energy supply. If fats play a larger role in neuronal energy than previously thought, therapies based on fatty acid supplements could provide a new way to treat illnesses once considered untreatable.
The next step, according to Dr. Joensuu, is to test the safety and effectiveness of these fatty acid treatments in preclinical studies, an essential stage before moving into human trials. Researchers will also investigate whether the same fat-based energy pathway is involved in other neurological conditions.
“This discovery gives us real hope,” Dr. Joensuu said. “By better understanding the brain’s hidden fuel system, we may finally have a way to fight diseases that have resisted treatment for far too long.”
