高级检索
当前位置: 首页 > 详情页

Reprogramming of rhythmic liver metabolism by intestinal clock

文献详情

资源类型:
WOS体系:
Pubmed体系:

收录情况: ◇ SCIE

机构: [1]Institute of Molecular Rhythm and Metabolism, Guangzhou University of Chinese Medicine, Guangzhou, China. [2]Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. [3]Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University , The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China.
出处:
ISSN:

摘要:
Temporal oscillations in intestinal nutrient processing and absorption are coordinated by the local clock, which leads to the hypothesis that intestine clock has major impact on shaping peripheral rhythms via diurnal nutritional signals. Here we investigate the role of intestine clock in controlling liver rhythmicity and metabolism.Transcriptomic analysis, metabolomics, metabolic assays, histology, qPCR, and immunoblotting were performed with Bmal1-iKO (intestine-specific knockout of Bmal1), Rev-erbα-iKO and control mice.Bmal1-iKO causes a large-scale reprogramming of the rhythmic transcriptome of mouse liver with a limited effect on its clock. In the absence of intestinal Bmal1, liver clock is resistant to the entrainment by inverted feeding and high-fat diet. Importantly, Bmal1-iKO remodels diurnal hepatic metabolism by shifting to gluconeogenesis from lipogenesis in the dark phase, leading to elevated glucose production (hyperglycemia) and insulin insensitivity. Conversely, Rev-erbα-iKO causes a diversion to lipogenesis from gluconeogenesis in the light phase, resulting in enhanced lipogenesis and an increased susceptibility to alcoholic liver injury. These temporal diversions are attributed to a disruption of hepatic SREBP-1c rhythmicity, which is maintained via gut-derived polyunsaturated fatty acids produced by intestinal FADS1/2 under the control of local clock.Our findings establish a pivotal role of intestine clock in dictating liver rhythmicity and diurnal metabolism, and suggest targeting intestinal rhythms as a new avenue for improving metabolic health.Our findings establish the centrality of the intestine clock amongst peripheral tissue clocks, and associate liver-related pathologies with malfunction of intestine clock. Clock modifiers in the intestine are shown to modulate liver metabolism with improved metabolic parameters. The knowledge will help the clinicians improve the diagnosis and treatment of metabolic diseases by incorporating intestinal circadian factors.Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

基金:
语种:
WOS:
PubmedID:
中科院(CAS)分区:
出版当年[2022]版:
大类 | 1 区 医学
小类 | 1 区 胃肠肝病学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 胃肠肝病学
JCR分区:
出版当年[2021]版:
Q1 GASTROENTEROLOGY & HEPATOLOGY
最新[2023]版:
Q1 GASTROENTEROLOGY & HEPATOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者:
第一作者机构: [1]Institute of Molecular Rhythm and Metabolism, Guangzhou University of Chinese Medicine, Guangzhou, China.
共同第一作者:
通讯作者:
推荐引用方式(GB/T 7714):
APA:
MLA:

资源点击量:2018 今日访问量:0 总访问量:645 更新日期:2024-07-01 建议使用谷歌、火狐浏览器 常见问题

版权所有©2020 广东省中医院 技术支持:重庆聚合科技有限公司 地址:广州市越秀区大德路111号