Date of Award

January 2023

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biomedical Sciences

First Advisor

Eric J. Murphy

Abstract

Previous studies have shown that sterol carrier protein 2 (SCP-2) and sterol carrier protein x (SCP-x) are important for mediating the transfer of phospholipids, cholesterol and other sterols within the cell. However, the differences between males and females regarding the impact SCP2 has on brain and liver lipid metabolism is unknown. To further understand this, we profiled the effects of SCP2 gene ablation on brain and liver lipid metabolism in male and female mice fed a high fat diet or control diet and analyzed phospholipid and neutral lipid mass and composition using HPLC and TLC. In brains of male mice, SCP2 gene ablation led to significant increase in brain phosphatidylcholine (PtdCho), and an overall increase in total phospholipid levels in male mice fed a high cholesterol diet. In brains of female mice, there was a significant reduction in cholesterol compared to male mice. In liver, male mice fed a high cholesterol diet had a significant increase in total phospholipid mass accounted for by an increase in ChoGpl mass compared to mice fed a control diet and was seen in both wild type and gene-ablated mice. In both male and female mice there was between an increase in cholesteryl ester mass in mice fed a high cholesterol diet compared to mice fed a control diet. These results demonstrate that SCP2 facilitates brain and liver ChoGpl, cholesterol, and cholesteryl ester metabolism. Results also suggest that a high cholesterol diet increases cholesterol ester synthesis in the liver where SCP-2 and SCP-x is important for regulating lipid metabolism. There may also be sex-specific differences in liver and brain lipid metabolism and steady-state lipids levels.

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