Circadian Clock Regulation of Hepatic Energy Metabolism Regulatory Circuits

The liver is a critical organ of energy metabolism. At least 10% of the liver transcriptome demonstrates rhythmic expression, implying that the circadian clock regulates large programmes of hepatic genes. Here, we review the mechanisms by which this rhythmic regulation is conferred, with a particular focus on the transcription factors whose actions combine to impart liver- and time-specificity to metabolic gene expression.

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A human-mouse conserved sex bias in amygdala gene expression related to circadian clock and energy metabolism

Molecular Brain ◽

10.1186/1756-6606-4-18 ◽

2011 ◽

Vol 4 (1) ◽

pp. 18 ◽

Cited By ~ 18

Author(s):

Li-Chun Lin ◽

David A Lewis ◽

Etienne Sibille

Keyword(s):

Gene Expression ◽

Energy Metabolism ◽

Circadian Clock ◽

Sex Bias

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Growth Hormone Pulses and Liver Gene Expression Are Differentially Regulated by the Circadian Clock Gene Bmal1

Endocrinology ◽

10.1210/endocr/bqab023 ◽

2021 ◽

Vol 162 (4) ◽

Author(s):

Erica L Schoeller ◽

Karen J Tonsfeldt ◽

McKenna Sinkovich ◽

Rujing Shi ◽

Pamela L Mellon

Keyword(s):

Gene Expression ◽

Growth Hormone ◽

Circadian Clock ◽

Messenger Rna ◽

Clock Gene ◽

Serum Insulin ◽

Sexually Dimorphic ◽

Circadian Clock Gene ◽

Major Urinary Proteins ◽

Hepatic Genes

Abstract In this study, we found that loss of the circadian clock gene Bmal1 causes disruptions throughout the growth hormone (GH) axis, from hepatic gene expression to production of urinary pheromones and pheromone-dependent behavior. First, we show that Bmal1 knockout (KO) males elicit reduced aggressive responses from wild-type (WT) males and secrete lower levels of major urinary proteins (MUPs); however, we also found that a liver-specific KO of Bmal1 (liver-Bmal1-KO) produces a similar reduction in MUP secretion without a defect in aggressive behavior, indicating that the decrease in elicited aggression arises from another factor. We then shifted our investigation to determine the cause of MUP dysregulation in Bmal1 KO animals. Because the pulse pattern of GH drives sexually dimorphic expression of hepatic genes including MUPs, we examined GH pulsatility. We found that Bmal1 KO males have a female-like pattern of GH release, whereas liver-Bmal1-KO mice are not significantly different from either WT or Bmal1 KO. Since differential patterns of GH release regulate the transcription of many sexually dimorphic genes in the liver, we then examined hepatic gene transcription in Bmal1 KO and liver-Bmal1-KO mice. We found that while some female-predominant genes increase in the Bmal1 KO, there was no decrease in male-predominant genes, and little change in the liver-Bmal1-KO. We also found disrupted serum insulin growth factor 1 (IGF-1) and liver Igf1 messenger RNA in the Bmal1 KO mice, which may underlie the disrupted GH release. Overall, our findings differentiate between GH-pulse–driven and circadian-driven effects on hepatic genes, and the functional consequences of altered GH pulsatility.

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Phosphoenolpyruvate Carboxykinase Is Necessary for the Integration of Hepatic Energy Metabolism

Molecular and Cellular Biology ◽

10.1128/mcb.20.17.6508-6517.2000 ◽

2000 ◽

Vol 20 (17) ◽

pp. 6508-6517 ◽

Cited By ~ 152

Author(s):

Pengxiang She ◽

Masakazu Shiota ◽

Kathy D. Shelton ◽

Roger Chalkley ◽

Catherine Postic ◽

...

Keyword(s):

Energy Metabolism ◽

Phosphoenolpyruvate Carboxykinase ◽

Intermediary Metabolites ◽

Hepatic Energy Metabolism ◽

Genes Encoding ◽

Plasma Hormone ◽

Hepatic Genes ◽

Targeting Strategy ◽

Global Reduction

ABSTRACT We used an allelogenic Cre/loxP gene targeting strategy in mice to determine the role of cytosolic phosphoenolpyruvate carboxykinase (PEPCK) in hepatic energy metabolism. Mice that lack this enzyme die within 3 days of birth, while mice with at least a 90% global reduction of PEPCK, or a liver-specific knockout of PEPCK, are viable. Surprisingly, in both cases these animals remain euglycemic after a 24-h fast. However, mice without hepatic PEPCK develop hepatic steatosis after fasting despite up-regulation of a variety of genes encoding free fatty acid-oxidizing enzymes. Also, marked alterations in the expression of hepatic genes involved in energy metabolism occur in the absence of any changes in plasma hormone concentrations. Given that a ninefold elevation of the hepatic malate concentration occurs in the liver-specific PEPCK knockout mice, we suggest that one or more intermediary metabolites may directly regulate expression of the affected genes. Thus, hepatic PEPCK may function more as an integrator of hepatic energy metabolism than as a determinant of gluconeogenesis.

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Effects of Endurance Exercise and Rapamycin on Hepatic Energy Metabolism Gene Expression in Rats Fed a High-Fat Diet

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000518078.95760.34 ◽

2017 ◽

Vol 49 (5S) ◽

pp. 436

Author(s):

Bagen Liao ◽

Yanfei Li

Keyword(s):

Gene Expression ◽

Energy Metabolism ◽

Endurance Exercise ◽

High Fat Diet ◽

High Fat ◽

Hepatic Energy Metabolism ◽

Metabolism Gene

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Altered energy metabolism and metabolic gene expression associated with increased metastatic capacity identified in MDA-MB-231 cell line variants

Journal of Cancer Metastasis and Treatment ◽

10.20517/2394-4722.2018.67 ◽

2018 ◽

Vol 2018 ◽

Cited By ~ 2

Author(s):

Yan Tu ◽

Cameron N. Johnstone ◽

James G. Ryall ◽

Guillermo H. López-Campos ◽

Christine R. Keenan ◽

...

Keyword(s):

Gene Expression ◽

Energy Metabolism ◽

Cell Line ◽

Metabolic Gene ◽

Metabolic Gene Expression ◽

Metastatic Capacity

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Genome-wide analysis of PRR gene family uncovers their roles in circadian rhythmic changes and response to drought stress in Gossypium hirsutum L.

PeerJ ◽

10.7717/peerj.9936 ◽

2020 ◽

Vol 8 ◽

pp. e9936

Author(s):

Jingjing Wang ◽

Zhaohai Du ◽

Xuehan Huo ◽

Juan Zhou ◽

Yu Chen ◽

...

Keyword(s):

Gene Expression ◽

Drought Stress ◽

Circadian Clock ◽

Gene Family ◽

Expression Patterns ◽

Enrichment Analysis ◽

Tetraploid Cotton ◽

Diurnal Changes ◽

Rhythmic Expression ◽

Qrt Pcr

Background The circadian clock not only participates in regulating various stages of plant growth, development and metabolism, but confers plant environmental adaptability to stress such as drought. Pseudo-Response Regulators (PRRs) are important component of the central oscillator (the core of circadian clock) and play a significant role in plant photoperiod pathway. However, no systematical study about this gene family has been performed in cotton. Methods PRR genes were identified in diploid and tetraploid cotton using bioinformatics methods to investigate their homology, duplication and evolution relationship. Differential gene expression, KEGG enrichment analysis and qRT-PCR were conducted to analyze PRR gene expression patterns under diurnal changes and their response to drought stress. Results A total of 44 PRR family members were identified in four Gossypium species, with 16 in G. hirsutum, 10 in G. raimondii, and nine in G. barbadense as well as in G. arboreum. Phylogenetic analysis indicated that PRR proteins were divided into five subfamilies and whole genome duplication or segmental duplication contributed to the expansion of Gossypium PRR gene family. Gene structure analysis revealed that members in the same clade are similar, and multiple cis-elements related to light and drought stress response were enriched in the promoters of GhPRR genes. qRT-PCR results showed that GhPRR genes transcripts presented four expression peaks (6 h, 9 h, 12 h, 15 h) during 24 h and form obvious rhythmic expression trend. Transcriptome data with PEG treatment, along with qRT-PCR verification suggested that members of clade III (GhPRR5a, b, d) and clade V (GhPRR3a and GhPRR3c) may be involved in drought response. This study provides an insight into understanding the function of PRR genes in circadian rhythm and in response to drought stress in cotton.

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