Effect of chronic intermittent hypoxia on hippocampal lipid metabolism in mice: A targeted lipidomics study

Abstract

Evidence suggests that cognitive impairments due to obstructive sleep apnea (OSA) are related to abnormal lipid metabolism. Abnormal lipid metabolism in the brain might be a potential cause of neurodegeneration. Nonetheless, there is limited clarity regarding the comprehensive lipid metabolism changes in the hippocampus induced by chronic intermittent hypoxia (CIH). Targeted lipidomic analysis of mouse hippocampus and HT22 cells was essential to exploring changes in lipid metabolism after CIH exposure. The approach was used to quantify 575 lipid species in mouse hippocampus and 1285 lipid species in HT22 cells, belonging to 6 different classes. Among those lipid classes, glycerophospholipids (GP), fatty acyls (FA), sphingolipids (SP), glycerolipid (GL), and prenol lipids (PR) were not significantly changed in mouse hippocampus under CIH conditions, but steroid (ST) levels were significantly reduced. Based on in vitro results, CIH exposure significantly raises the levels of several lipids, including GP, PR, SP, and ST. However, GL and FA did not change significantly. Notably, in vivo as well as in vitro experiments showed down-regulation of LPI (16:0), LPI (18:0), PC (18:1/20:4), PE (O-18:0/16:0), PE (O-16:0/22:6), PI (18:0/18:0), and up-regulation of PI (18:0/19:2). Additionally, in CIH conditions, lipid droplets (LDs) typically accumulate as a result of metabolism disorders. Disorders of lipid metabolism and the abnormal accumulation of LDs in neurons cause neuronal damage and behavioral disorders. The altered levels of LPI, PC, PE, and PI in OSA patients might provide new insights into understanding lipid metabolism disorders in the nervous system.