ApoE-dependent lipid handling by median eminence microglia supports myelin remodeling and metabolic function.

ApoE-dependent lipid-handling programs in median eminence microglia are linked to myelin remodeling and metabolic function, and are intensified by Western diet and APOE4.

• Why it matters: Microglia help control hypothalamic regulation of systemic metabolism, but how ApoE shapes their adaptive responses to metabolic stress is unclear.
• What they did: The study mapped ApoE-associated microglial transcriptional states enriched in the median eminence, then tested Western diet effects, human APOE4 expression, Apoe deletion, and liver X receptor activation with sHDL nanoparticles in WD-fed mice.
• The result: Western diet increased microglial lipid accumulation and altered myelin remodeling in the median eminence, APOE4 exacerbated these changes, Apoe deletion shifted responses to nutritional stress, and sHDL enhanced lipid-handling programs while improving leptin responsiveness, reducing food intake, and limiting weight gain.

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