Cloning and mRNA tissue distribution of human PPARgamma coactivator-1.

To determine human PPARgamma coactivator-1 (PGC-1) amino acid sequence and to study PGC-1 mRNA tissue distribution. PGC-1 is a novel transcriptional coactivator of nuclear receptors that may play a role in the control of thermogenesis. Subcutaneous adipose tissue was obtained from six obese and five lean male subjects. Vastus lateralis skeletal muscle was obtained from seven lean and six obese subjects undergoing a 5-day severe calorie restriction. Other tissue biopsies were from nonobese nondiabetic subjects. Human PGC-1 was cloned from a skeletal muscle cDNA library. A reverse transcription-competitive polymerase chain reaction assay was developed to determine PGC-1 mRNA levels in human tissues. The human amino acid sequence showed 95% identity with mouse PGC-1. PGC-1 mRNA was expressed at very low levels in the small and large intestines and white adipose tissue. Heart, kidney, liver and skeletal muscle showed higher mRNA levels. The degree of obesity did not affect PGC-1 mRNA levels in adipose tissue while lean subjects expressed more PGC-1 mRNA than obese subjects in skeletal muscle. A 5-day severe calorie restriction induced PGC-1 mRNA expression in skeletal muscle of obese but not of lean subjects. PGC-1 shows a restricted tissue expression that suggests a tissue-specific role in the control of gene transcription and possible interaction with various members of the PPAR family. The lower expression of skeletal muscle PGC-1 in obesity could contribute to an alteration of mitochondrial gene expression.