Organization and Evolution of Brain Lipidome Revealed by Large-Scale Analysis of Human, Chimpanzee, Macaque, and Mouse Tissues

• Brain lipid composition is distinct from that of non-neural tissues
• The lipidome complexity of the brain increases from mice to humans
• Lipid concentrations evolved four times faster in brain than in non-neural tissues
• Evolution of brain lipid concentrations is further accelerated in the human neocortex

SummaryLipids are prominent components of the nervous system. Here we performed a large-scale mass spectrometry-based analysis of the lipid composition of three brain regions as well as kidney and skeletal muscle of humans, chimpanzees, rhesus macaques, and mice. The human brain shows the most distinct lipid composition: 76% of 5,713 lipid compounds examined in our study are either enriched or depleted in the human brain. Concentration levels of lipids enriched in the brain evolve approximately four times faster among primates compared with lipids characteristic of non-neural tissues and show further acceleration of change in human neocortical regions but not in the cerebellum. Human-specific concentration changes are supported by human-specific expression changes for corresponding enzymes. These results provide the first insights into the role of lipids in human brain evolution.Video Abstract To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowHelp with MP4 filesOptionsDownload video (9752 K)