Glycolytically impaired Drosophila glial cells fuel neural metabolism via β-oxidation

Neuronal function is highly energy demanding and thus requires efficient and constant metabolite delivery by glia. Drosophila glia are highly glycolytic and provide lactate to fuel neuronal metabolism. Flies are able to survive for several weeks in the absence of glial glycolysis. Here, we study how Drosophila glial cells maintain sufficient nutrient supply to neurons under conditions of impaired glycolysis. We show that glycolytically impaired glia rely on mitochondrial fatty acid breakdown and ketone body production to nourish neurons, suggesting that ketone bodies serve as an alternate neuronal fuel to prevent neurodegeneration. We show that in times of long-term starvation, glial degradation of absorbed fatty acids is essential to ensure survival of the fly. Further, we show that Drosophila glial cells act as a metabolic sensor and can induce mobilization of peripheral lipid stores to preserve brain metabolic homeostasis. Our study gives evidence of the importance of glial fatty acid degradation for brain function, and survival, under adverse conditions in Drosophila.