Transcriptional coactivator PGC-1α integrates the mammalian clock and energy metabolism

Liu, Chang; Li, Siming; Liu, Tiecheng; Borjigin, Jimo; Lin, Jiandie D.

doi:10.1038/nature05767

Cited by 643Circadian rhythm and melatoninAdipose Tissue and MetabolismPeroxisome Proliferator-Activated Receptors

Transcriptional coactivator PGC-1α integrates the mammalian clock and energy metabolism

Liu, Chang, Li, Siming, Liu, Tiecheng, Borjigin, Jimo, Lin, Jiandie D.·2007·Nature

DOI 10.1038/nature05767

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Abstract

The mammalian clock regulates major aspects of energy metabolism, including glucose and lipid homeostasis and mitochondrial oxidative metabolism. The biochemical basis for coordinated control of the circadian clock and diverse metabolic pathways is not well understood. Here we show that PGC-1alpha (Ppargc1a), a transcriptional coactivator that regulates energy metabolism, is rhythmically expressed in the liver and skeletal muscle of mice. PGC-1alpha stimulates the expression of clock genes, notably Bmal1 (Arntl) and Rev-erbalpha (Nr1d1), through coactivation of the ROR family of orphan nuclear receptors. Mice lacking PGC-1alpha show abnormal diurnal rhythms of activity, body temperature and metabolic rate. The disruption of physiological rhythms in these animals is correlated with aberrant expression of clock genes and those involved in energy metabolism. Analyses of PGC-1alpha-deficient fibroblasts and mice with liver-specific knockdown of PGC-1alpha indicate that it is required for cell-autonomous clock function. We have thus identified PGC-1alpha as a key component of the circadian oscillator that integrates the mammalian clock and energy metabolism.

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Output from the suprachiasmatic nucleus is capable of producing sustained and synchronous cellular rhythmicity in both central and peripheral tissues, resulting in the temporal organization of molecular and behavioral rhythms throughout the body.
“Output from the SCN is capable of producing sustained and synchronous cellular rhythmicity in both central and peripheral tissues, resulting in the temporal organization of molecular and behavioral rhythms throughout the body (Liu et al., 2007).”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Liu et al., 2007
PGC-1α has been proposed as a link between the mammalian circadian clock and energy metabolism.
“Recently, the transcriptional coactivator PGC-1α has been proposed as a link between the mammalian circadian clock and energy metabolism (Liu et al., 2007).”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Liu et al., 2007

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Authors: Liu, C., Li, S., Liu, T., Borjigin, J., & Lin, J. D.
Affiliations: University of Michigan (US)
Life Sciences Institute (SG)
Corresponding author: Lin, Jiandie D.
ORCID: Liu, Chang
Li, Siming
Liu, Tiecheng
Borjigin, Jimo
Lin, Jiandie D.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2007-05
Volume: 447
Issue: 7143
Pages: 477-481
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature05767
OpenAlex: W1993901564
Cited by: 643
References: 30
Citations by year: 2026: 20 · 2025: 16 · 2024: 31 · 2023: 21 · 2022: 28 · 2021: 18 · 2020: 42 · 2019: 32 · 2018: 24 · 2017: 34 · 2016: 30 · 2015: 39 · 2014: 38 · 2013: 47 · 2012: 39
FWCI: 19.03
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Deep Blue (University of Michigan) (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords: PGC-1α, circadian clock, energy metabolism, clock genes, Bmal1, NR1D1, transcriptional coactivator, diurnal cycle, body temperature, metabolic rate, liver, skeletal muscle, cell-autonomous clock, glucose homeostasis, lipid homeostasis, mitochondrial oxidative metabolism
MeSH terms: Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Biological Clocks, Body Temperature, Circadian Rhythm, Darkness, DNA-Binding Proteins, Energy Metabolism, Fibroblasts, Gene Expression Regulation, Light, Liver, Mice, Inbred C57BL, Motor Activity, Transcription Factors, Transcription, Genetic, Trans-Activators, Gene Deletion, Receptors, Cytoplasmic and Nuclear, Muscle, Skeletal, Mice, Aryl Hydrocarbon Receptor Nuclear Translocator, ARNTL Transcription Factors, Nuclear Receptor Subfamily 1, Group D, Member 1

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Transcriptional coactivator PGC-1α integrates the mammalian clock and energy metabolism

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