Scientists from the University of Queensland and the University of Helsinki have uncovered a groundbreaking discovery thatneuronsuse fat, not just sugar, as a crucial energy source. Traditionally, brain energy metabolism was believed to rely solely on glucose, but these researchers demonstrated that neurons can burn fat by producingfatty acidsthemselves through a recycling process regulated by a protein called DDHD2. This metabolic flexibility supports neuronal activity, especially when energy demands increase. The research is published in the journalNature Metabolism. For a long time, it was believed that the brain relies almost entirely on glucose, a type of sugar, for its energy needs. However, new research shows that neurons—the brain's nerve cells—can also use fat as a fuel. They do this by making their own fatty acids through a recycling process controlled by a special protein called DDHD2. This protein helps neurons break down parts of their own cells to produce fat molecules, which provide energy, especially when the brain's demand for fuel increases. This discovery reveals that neurons have a flexible energy system, allowing them to burn fat as well as sugar, which could be important forbrain healthand function. Their research employed advanced biochemical assays and imaging techniques to study isolated neurons and animal models. When glucose availability dropped, or energy demand rose, neurons tapped into lipid droplets-energy-rich fat stores-to sustain mitochondrial function and ATP production. The key protein DDHD2 facilitates this fat metabolism. Mutations in DDHD2 cause the rare neurological disorder Hereditary Spastic Paraplegia 54 (HSP54), where impaired fat metabolism leads to neuronal energy failure, cognitive deficits, and mobility problems. Remarkably, supplying damaged neurons with specific fatty acid supplements restored energy production and normalized cellular activity within 48 hours in laboratory settings. This points to therapeutic potential for fat-based interventions in neurodegenerative diseases lacking effective treatments. Lead researcher Dr. Merja Joensuu called the findings “a game-changer,” emphasizing that recognizing fat as a vital brain fuel opens new research and treatment avenues. The team plans to test fatty acid therapies' safety and efficacy in preclinical models and use innovative noninvasive brain imaging to speed therapy development. Reference:Saber H. Saber, Nyakuoy Yak, Xuan Ling Hilary Yong, Yih Tyng Bong, Hannah Leeson, Chuan-Yang Dai, Tobias Binder, Siyuan Lu, Reshinthine Purushothaman, An-Sofie Lenaerts, Leonardo Almeida-Souza, Lidiia Koludarova, Safak Er, Irena Hlushchuk, Arnaud Gaudin, Sachin Singh, Tuula A. Nyman, Jeffrey R. Harmer, Steven Zuryn, Ernst Wolvetang, Gert Hoy Talbo, Mikko Airavaara, Brendan J. Battersby, Ashley J. van Waardenberg, Victor Anggono, Giuseppe Balistreri, Merja Joensuu. DDHD2 provides a flux of saturated fatty acids for neuronal energy and function. Nature Metabolism, 2025; 7 (10): 2117 DOI: 10.1038/s42255-025-01367-x