Research from Weill Cornell Medicine, published on July 1, 2025, reveals a groundbreaking shift in understanding brain energy sources, showing that brain cells can utilize fat droplets as an energy source, challenging the traditional belief that the brain exclusively relies on glucose.

This research opens avenues for exploring the relationship between lipids and neurodegenerative diseases, suggesting that fatty acids from lipid droplets could help maintain brain energy levels during glucose fluctuations.

In experiments, blocking the enzyme carnitine palmitoyltransferase 1 (CPT1), crucial for transporting fatty acids into mitochondria, induced a hibernation-like state in mice, reinforcing the brain's reliance on lipid droplets for energy.

The study found that electrical activity in neurons drives the consumption of fat droplets, with active neurons metabolizing fats while resting neurons do not engage in this process.

Experiments demonstrated that neurons can convert triglycerides from lipid droplets into fatty acids, which are then utilized in mitochondria to produce ATP, the energy currency of cells.

Findings indicate that in mice lacking the DDHD2 enzyme, lipid droplets accumulate, and neurons can convert these fats into fatty acids for energy production in mitochondria, particularly when glucose is unavailable.

The research focuses on the DDHD2 gene, which encodes an enzyme that breaks down fats; mutations in this gene are associated with hereditary spastic paraplegia, leading to neurological symptoms.

Principal investigator Dr. Timothy A. Ryan and lead author Dr. Mukesh Kumar led the study, emphasizing the significance of lipid metabolism in brain energy supply, akin to its role in muscle tissues.

Dr. Mukesh Kumar highlights that this finding aligns with the metabolic needs of the brain, similar to other demanding tissues like muscles.

Further investigation is needed to understand the links between lipid accumulation in neurons and conditions like Parkinson's disease, as well as the interactions between glucose and lipids in brain metabolism.