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Dietary Sterols and Sterol Oxidation Products On Atherosclerosis: An Insight Provided By Liver Proteomic and Lipidomic.

SCOPE
The development of atherosclerosis is closely associated with disorder of lipid metabolism. Dietary sterols and their oxidation products play a role in the pathogenesis of atherosclerosis. However, their effects on liver lipid metabolism during the atherosclerosis remain unknown.


METHODS AND RESULTS
Here, we applied lipidomic and proteomic analysis on liver of ApoE-/- mice fed with phytosterols, cholesterol oxidation products (COPs) or phytosterol oxidation products (POPs) to profile lipid species and reveal the underlying mechanism. Dietary exposure of phytosterols, COPs and POPs all reduced the accumulation of liver triglyceride (TG), but COPs and POPs accelerated the fibrosis of liver. Lipidomic analysis revealed that phytosterols mainly decreased the levels of phosphatidylinositol (PI), while COPs and POPs both increased the level of digalactosyldiacylglycerol (DGDG) and reduced TG with long-chain polyunsaturated fatty acids. Besides, COPs up-regulated levels of lipids associated with atherosclerosis risk, such as phosphatidylcholines (PC), phosphatidylethanolamine (PE) and ceramides (Cer). POPs down-regulated the level of acyl carnitine (AcCa). Furthermore, proteomic analysis showed that COPs promoted oxidative phosphorylation and POPs inhibited the beta oxidation of fatty acids.


CONCLUSIONS
This study revealed that phytosterols, COPs and POPs differently changed the composition and metabolism of glycerophospholipids, sphingolipids and glycerolipids in liver of ApoE-/- mice. This article is protected by copyright. All rights reserved.