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DOI10.1126/SCIENCE.ABA8984
The hepatocyte clock and feeding control chronophysiology of multiple liver cell types
Guan D.; Xiong Y.; Trinh T.M.; Xiao Y.; Hu W.; Jiang C.; Dierickx P.; Jang C.; Rabinowitz J.D.; Lazar M.A.
发表日期2020
ISSN0036-8075
起始页码1388
结束页码1395
卷号369期号:6509
英文摘要Most cells of the body contain molecular clocks, but the requirement of peripheral clocks for rhythmicity and their effects on physiology are not well understood. We show that deletion of core clock components REV-ERBa and REV-ERBb in adult mouse hepatocytes disrupts diurnal rhythms of a subset of liver genes and alters the diurnal rhythm of de novo lipogenesis. Liver function is also influenced by nonhepatocytic cells, and the loss of hepatocyte REV-ERBs remodels the rhythmic transcriptomes and metabolomes of multiple cell types within the liver. Finally, alteration of food availability demonstrates the hierarchy of the cell-intrinsic hepatocyte clock mechanism and the feeding environment. Together, these studies reveal previously unsuspected roles of the hepatocyte clock in the physiological coordination of nutritional signals and cell-cell communication controlling rhythmic metabolism. © 2020 The Authors.
英文关键词cryptochrome 1; insulin; kruppel like factor; kruppel like factor 9; nuclear receptor NR1D1; PER2 protein; peroxisome proliferator activated receptor alpha; transcription factor ARNTL; transcription factor CLOCK; unclassified drug; cell receptor; Nr1d1 protein, mouse; Nr1d2 protein, mouse; nuclear receptor NR1D1; repressor protein; cell component; chronology; diurnal activity; food availability; metabolism; molecular analysis; physiology; adult; animal cell; animal experiment; Article; Bmal1 gene; cell communication; circadian rhythm; Clock gene; controlled study; Cry1 gene; Dhfr gene; endothelium cell; Enpp6 gene; enzyme regulation; feedback system; feeding behavior; gene; gene expression; high fat/high sucrose diet; hormone release; insulin blood level; Kupffer cell; lipid homeostasis; lipid metabolism; lipogenesis; liver cell; liver function; locomotion; metabolomics; mouse; nonhuman; Npas2 gene; Per2 gene; priority journal; Rev erba gene; Rev erbB gene; reverse phase feeding; RNA sequence; signal transduction; Slc25a51 gene; transcriptomics; animal; C57BL mouse; circadian rhythm; gene deletion; gene expression regulation; genetics; knockout mouse; liver; liver cell; physiology; Animals; Cell Communication; Circadian Clocks; Circadian Rhythm; Feeding Behavior; Gene Deletion; Gene Expression Regulation; Hepatocytes; Liver; Mice; Mice, Inbred C57BL; Mice, Knockout; Nuclear Receptor Subfamily 1, Group D, Member 1; Receptors, Cytoplasmic and Nuclear; Repressor Proteins
语种英语
来源期刊Science
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/243890
作者单位Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Lewis-Sigler Institute for Integrative Genomics, Department of Chemistry, Princeton University, Princeton, NJ 08544, United States; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Biological Chemistry, University of California Irvine, Irvine, CA 92697, United States
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Guan D.,Xiong Y.,Trinh T.M.,et al. The hepatocyte clock and feeding control chronophysiology of multiple liver cell types[J],2020,369(6509).
APA Guan D..,Xiong Y..,Trinh T.M..,Xiao Y..,Hu W..,...&Lazar M.A..(2020).The hepatocyte clock and feeding control chronophysiology of multiple liver cell types.Science,369(6509).
MLA Guan D.,et al."The hepatocyte clock and feeding control chronophysiology of multiple liver cell types".Science 369.6509(2020).
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