Per1/Per2 double knockout transcriptome analysis reveals circadian regulation of hepatic lipid metabolism  

作　　者：Yiran Bu Si Chen Mengcheng Ruan Libang Wu Hualin Wang Na Li Xiuju Zhao Xiaoli Yu Zhiguo Liu 

机构地区：[1]Hubei Province Engineering Research Center of Healthy Food,School of Biology and Pharmaceutical Engineering,Wuhan Polytechnic University,Wuhan 430023,China

出　　处：《Food Science and Human Wellness》2023年第5期1716-1729,共14页食品科学与人类健康（英文）

基　　金：supported by National Natural Science Foundation of China (31271855);the ThirteenFifth Mega-Scientific Project (2017ZX10201301-003-003);Wuhan science and technology project (2018020402011230);the central government guides local science and technology development projects (2019ZYYD)。

摘　　要：Scope: Circadian disorder and high-fat diet(HFD)can disturb lipid metabolism homeostasis and may promote the development of various metabolic diseases. The relationship between them is of great concern. This study aimed to explore the effects of Per1/Per2 double knockout(DKO)on hepatic lipid metabolism in mice under HFD and HFD with docosahexaenoic acid(DHA)substitution. Methods and results: Both wild type(WT)and DKO male C57BL/6 mice were fed with normal chow diet(CON), HFD, or HFD with DHA substitution(AO)for 15 weeks. At the end of the experiment, mice were sacrificed at zeitgeber time(ZT)0(7:00 am)or ZT12(7:00 pm). Pathological indicators were determined using histological and biochemical methods. Hepatic transcriptome sequencing analysis showed that DKO mice exhibited multiple dysfunctions in diurnal rhythm, drug metabolism, cell cycle, cancer pathways, and lipid metabolism. HFD had greater effects on fatty acid oxidation and cholesterol synthesis and metabolism in Per1-/-Per2-/-mice, which was improved by DHA substitution. Conclusions: Per1/Per2 played an important role in the circadian regulation of hepatic lipid metabolism, and DKO mice were more sensitive to HFD. DHA can improve circadian-related lipid metabolism disruption induced by HFD in mice.

关 键 词：DHA High-fat diet Lipid metabolism Per1/Per2 TRANSCRIPTOMICS 

分 类 号：R575.5[医药卫生—消化系统]