Excess dietary sugar profoundly impacts organismal metabolism and health, yet it remains unclear how metabolic adaptations in adipose tissue influence other organs, including the brain. Here, we show Show more
Excess dietary sugar profoundly impacts organismal metabolism and health, yet it remains unclear how metabolic adaptations in adipose tissue influence other organs, including the brain. Here, we show that a high-sugar diet (HSD) in Drosophila reduces adipocyte glycolysis and mitochondrial pyruvate uptake, shifting metabolism toward fatty acid oxidation and ketogenesis. These metabolic changes trigger mitochondrial oxidation and elevate antioxidant responses. Adipocyte-specific manipulations of glycolysis, lipid metabolism, or mitochondrial dynamics non-autonomously modulate Draper expression in brain ensheathing glia, key cells responsible for neuronal debris clearance. Adipocyte-derived ApoB-containing lipoproteins maintain basal Draper levels in glia via LpR1, critical for effective glial phagocytic activity. Accordingly, reducing ApoB or LpR1 impairs glial clearance of degenerating neuronal debris after injury. Collectively, our findings demonstrate that dietary sugar-induced shifts in adipocyte metabolism substantially influence brain health by modulating glial phagocytosis, identifying adipocyte-derived ApoB lipoproteins as essential systemic mediators linking metabolic state with neuroprotective functions. Show less