Cell-Type- and Brain-Region-Resolved Mouse Brain Lipidome.

Fitzner, Dirk; Bader, Jakob M; Penkert, Horst; Bergner, Caroline G; Su, Minhui; Weil, Marie-Theres; Surma, Michal A; Mann, Matthias; Klose, Christian; Simons, Mikael

Gene and protein expression data provide useful resources for understanding brain function, but little is known about the lipid composition of the brain. Here, we perform quantitative shotgun lipidomics, which enables a cell-type-resolved assessment of the mouse brain lipid composition. We quantify around 700 lipid species and evaluate lipid features including fatty acyl chain length, hydroxylation, and number of acyl chain double bonds, thereby identifying cell-type- and brain-region-specific lipid profiles in adult mice, as well as in aged mice, in apolipoprotein-E-deficient mice, in a model of Alzheimer's disease, and in mice fed different diets. We also integrate lipid with protein expression profiles to predict lipid pathways enriched in specific cell types, such as fatty acid β-oxidation in astrocytes and sphingolipid metabolism in microglia. This resource complements existing brain atlases of gene and protein expression and may be useful for understanding the role of lipids in brain function.