Abstract
Adaptive thermogenesis is an important component of energy homeostasis and a metabolic defense against obesity. We have cloned a novel transcriptional coactivator of nuclear receptors, termed PGC-1, from a brown fat cDNA library. PGC-1 mRNA expression is dramatically elevated upon cold exposure of mice in both brown fat and skeletal muscle, key thermogenic tissues. PGC-1 greatly increases the transcriptional activity of PPARgamma and the thyroid hormone receptor on the uncoupling protein (UCP-1) promoter. Ectopic expression of PGC-1 in white adipose cells activates expression of UCP-1 and key mitochondrial enzymes of the respiratory chain, and increases the cellular content of mitochondrial DNA. These results indicate that PGC-1 plays a key role in linking nuclear receptors to the transcriptional program of adaptive thermogenesis.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptation, Physiological / physiology*
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Adipose Tissue, Brown / chemistry
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Adipose Tissue, Brown / metabolism
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Adrenergic beta-Agonists / pharmacology
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Amino Acid Sequence
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Animals
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Body Temperature Regulation / physiology*
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Cloning, Molecular
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Cold Temperature*
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Energy Metabolism / physiology
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Gene Expression Regulation / drug effects
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Male
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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RNA, Messenger / metabolism
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Receptors, Cytoplasmic and Nuclear / metabolism
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Receptors, Cytoplasmic and Nuclear / physiology*
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Transcription, Genetic / physiology
Substances
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Adrenergic beta-Agonists
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RNA, Messenger
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Receptors, Cytoplasmic and Nuclear
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Transcription Factors
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peroxisome-proliferator-activated receptor-gamma coactivator-1