Direct quantification of the metabolic heat output of individual Drosophila brains

Quantitative insights into brain metabolism are essential for advancing our understanding of energy dynamics in the brain. However, current approaches for tracking brain metabolism, metabolic profiling and respirometry, provide only static snapshots of metabolite levels or lack the required resolution. Here, we develop a novel nanowatt-resolution biocalorimeter capable of real-time continuous measurements of heat output to quantitatively measure the metabolism of individual live Drosophila melanogaster brains and investigate how sex, genotype, age, and disease affect brain metabolism. We show for the first time that female brains, across multiple wild-type genotypes, exhibit a significantly higher metabolic rate (∼10%) 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. Furthermore, we measure the metabolic rate of reproductive tissues of Drosophila , highlighting the broad applicability of our biocalorimeter. Together, these advances open new avenues for investigating how tissue-specific metabolism is impacted by aging, neurodegeneration, and disease states.