Differential proteomic analysis of mouse cerebrums with high-fat diet (HFD)-induced hyperlipidemia

Abstract

Hyperlipidemia is a chronic disease characterized by elevated blood cholesterol and triglycerides and there is accumulated evidence that the disease might affect brain functions. Here we report on a proteomic analysis of the brain proteins in hyperlipidemic mice. Hyperlipidemia was successfully induced in mice by a 20 week high-fat diet (HFD) feeding (model group). A control group with a normal diet and a treatment group with HFD-fed mice treated with a lipid-lowering drug simvastatin (SIM) were established accordingly. The proteins were extracted from the left and right cerebrum hemispheres of the mice in the three groups and subjected to shotgun proteomic analysis. A total of 4,422 proteins were detected in at least half of the samples, among which 324 proteins showed significant difference (fold change >1.5 or <0.67, p < 0.05) in at least one of the four types of comparisons (left cerebrum hemispheres of the model group versus the control group, right cerebrums of model versus control, left cerebrums of SIM versus model, right cerebrums of SIM versus model). Biological process analysis revealed many of these proteins were enriched in the processes correlated with lipid metabolism, neurological disorders, synaptic events and nervous system development. For the first time, it has been reported that some of the proteins have been altered in the brain under the conditions of HFD feeding, obesity or hyperlipidemia. Further, 22 brain processes-related proteins showed different expression in the two cerebrum hemispheres, suggesting changes of the brain proteins caused by hyperlipidemia might also be asymmetric. We hope this work will provide useful information to understand the effects of HFD and hyperlipidemia on brain proteins.