Proteomic analysis of liver in diet-induced Hyperlipidemic mice under Fructus Rosa roxburghii action

Abstract

Fructus Rosae Roxburghii (FRR) has been considered as edible and medicinal fruit possessing antiatherosclerotic effect, but the mechanism is still unclear. HLP is material basis for AS formation. Under FRR action, TC, TG, LDL, HDL and ASI in serum were regulated to control level. Differentially expressed proteins in liver were analyzed by using TMT labeling and LC-MS/MS for better understanding the effect and molecular mechanism of FRR on diet-induced hyperlipidemic mice. In total, 4460 proteins were quantified, of which 469 proteins showed dramatic changes between each group. According to molecular functions, 25 differentially co-expressed proteins were divided into five categories: substance metabolism, energy transformation and signal transduction, transcription and translation, immune defense. 15 key proteins involved lipids metabolism, which were identified as Cyp7a1, Cyp3a11, Tm7sf2, COAT2, CSAD, RBP3, Lpin1, Dhrs4, Aldh1b1, GK, Acot 4, TSC22D1, PGFS, EHs, GSTM1. This suggested that FRR could maintain metabolic homeostasis by regulating the metabolism of fatty acids, biosynthesis of BAs and steroids, and production of LPOs. 20 oxidative lipids further confirmed their importance regulating lipids metabolism. It's first time potential antiatherosclerotic mechanism of FRR regulating blood lipids was explored from protein level, which is of great significance to explore new drug targets for AS. SIGNIFICANCE: Under the action of FRR juice, the blood lipids in mice were regulated to control level. By TMT proteomic analysis, the effect and molecular mechanism of FRR on diet-induced hyperlipidemic mice were further explored. 25 differentially co-expressed proteins obtained in three diet groups might cooperatively regulate the lipids metabolism and hepatic function of mice, thus maintaining the metabolism homeostasis. By lipidomics analysis, 20 oxidative lipids further confirmed the importance of ω-3 and ω-6 PUFAs in regulating the lipids metabolism. These findings provide an improved understanding for the regulation of FRR on the blood lipids and explores potential metabolic targets for AS prevention.

Keywords: Atherosclerosis; Fructus Rosae Roxburghii; Hyperlipidemia; TMT proteomic analysis.