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

作者机构：Hubei Province Engineering Research Center of Healthy FoodSchool of Biology and Pharmaceutical EngineeringWuhan Polytechnic UniversityWuhan 430023China 

出 版 物：《Food Science and Human Wellness》 (食品科学与人类健康（英文）)

年 卷 期：2023年第12卷第5期

页      面：1716-1729页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

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) 

主　　题：DHA High-fat diet Lipid metabolism Per1/Per2 Transcriptomics 

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.