Direct quantification of the metabolic heat output of individual Drosophila brains

Quantitative insights into brain metabolism are essential for advancing our understanding of the energy dynamics in the brain. Here, we present a nanowatt-resolution biocalorimeter capable of real-time metabolic heat output measurements of individual, live Drosophila melanogaster brains. Using this platform, we show that female brains, across multiple genotypes, exhibit a significantly higher metabolic rate (∼10%-15%) than male brains at a young age (<10 days old) and follow distinct metabolic trajectories across the lifespan. We also find that parkin mutants, a genetic model for Parkinson's disease, exhibit a ∼15% reduction in brain metabolic output relative to controls, revealing that defective mitophagy due to parkin deficiency affects brain metabolism. Further, we demonstrate that the metabolic output of a Drosophila brain is ∼2.5-fold higher than reproductive tissues like ovary and testis. Together, these advances open new avenues for investigating the impact of aging, neurodegeneration, and disease states on brain metabolism.