College of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong, China.
Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong, China.
Life Sci. 2021 Apr 15;271:119145. doi: 10.1016/j.lfs.2021.119145. Epub 2021 Feb 3.
The aim of this study is to provide new insights on the association of lipid metabolites, circadian genes and lipid metabolism associated genes in spontaneously hypertensive rats.
An untargeted lipidomics using ultrahigh performance liquid chromatography-mass spectrometry metabolomics was used to identify the differentially expressed lipid metabolites over 24 h in Spontaneously hypertensive rats (SHR) with reference to Wistar-Kyoto rats (WKY). The expression of circadian clock genes (Bmal1, Clock, Per1, Per2, Cry1, Cry2) and lipid metabolism related genes (Rev-erbα, Pparα and Sirt1) was analysed RT-qPCR.
Ten lipid metabolites with significant differences in their levels in SHR compared to WKY were identified. The levels of MG (25:0), PA (36:3) and PE (38:2) were lower and the levels of LysoPCs (20:0 and 20:3) and TGs (54:5, 59:12, 28:0, 60:10 and 60:13) were found to be higher in SHR. SHR showed obvious disorders in the expression of circadian genes and lipid metabolism associated genes. A strong association between the levels of lipid metabolites and circadian genes and lipid metabolism associated genes was found.
Rhythm genes may further affect the 24-hour lipid metabolism level of spontaneously hypertensive rats by mediating lipid metabolism associated genes. This research provides new insights on the association of lipid metabolites, circadian genes and lipid metabolism associated genes in SHR.
本研究旨在为自发性高血压大鼠（SHR）中脂质代谢物、昼夜节律基因和脂质代谢相关基因的关联提供新的见解。
采用超高效液相色谱-质谱联用非靶向脂质组学方法，以 Wistar-Kyoto 大鼠（WKY）为参照，鉴定 SHR 中 24 小时差异表达的脂质代谢物。采用 RT-qPCR 分析昼夜节律基因（Bmal1、Clock、Per1、Per2、Cry1、Cry2）和脂质代谢相关基因（Rev-erbα、Pparα 和 Sirt1）的表达。
与 WKY 相比，SHR 中有 10 种脂质代谢物的水平存在显著差异。MG（25:0）、PA（36:3）和 PE（38:2）的水平较低，而 LysoPCs（20:0 和 20:3）和 TGs（54:5、59:12、28:0、60:10 和 60:13）的水平较高。SHR 中昼夜节律基因和脂质代谢相关基因的表达明显紊乱。脂质代谢物水平与昼夜节律基因和脂质代谢相关基因之间存在很强的关联。
节律基因可能通过调节脂质代谢相关基因进一步影响自发性高血压大鼠的 24 小时脂质代谢水平。本研究为 SHR 中脂质代谢物、昼夜节律基因和脂质代谢相关基因的关联提供了新的见解。
