Isolation and lipidomic profiling of neuronal lipid droplets to unveil the lipid landscape of neurodegenerative disorders.

Blocking neuron-specific triglyceride lipase enlarges neuronal lipid droplets so they can be purified by sucrose-gradient flotation for lipidomic profiling in cultured primary neurons.

• Why it matters: Neuronal lipid droplets are linked to metabolic processes, but their submicron size and low abundance have limited isolation and chemical characterization needed to study neurodegenerative disorder relevance.
• What they did: The protocol inhibits neuron-specific triglyceride lipase to increase droplet size, then isolates droplets from cultured primary neurons and performs improved lipidomic analysis using liquid chromatography–mass spectrometry.
• The result: The workflow takes 3–4 weeks and yields a unique lipid composition map of purified neuronal lipid droplets, enabling future high-throughput integration to detect disease-specific lipid metabolism changes.

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