A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis.
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.
Pubmed ID: 9529258 RIS Download
Adaptation, Physiological | Adipose Tissue, Brown | Adrenergic beta-Agonists | Amino Acid Sequence | Animals | Body Temperature Regulation | Cloning, Molecular | Cold Temperature | Energy Metabolism | Gene Expression Regulation | Male | Mice | Mice, Inbred C57BL | Molecular Sequence Data | RNA, Messenger | Receptors, Cytoplasmic and Nuclear | Transcription Factors | Transcription, Genetic