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 trans criptional coactivator of nuclear receptors, termed PGC-1, from a brow n fat cDNA library. PGC-I mRNA expression is dramatically elevated upo n cola exposure of mice in both brown fat and skeletal muscle, key the rmogenic tissues. PGC-1 greatly increases the transcriptional activity of PPAR gamma and the thyroid hormone receptor on the uncoupling prot ein (UCP-1) promoter. Ectopic expression of PGC-1 in white adipose cel ls 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 nu clear receptors to the transcriptional program of adaptive thermogenes is.