Human peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene:: cDNA sequence, genomic organization, chromosomal localization, and tissue expression

Brown adipose and muscle tissues can increase energy expenditure via adaptive thermogenesis, thereby protecting against obesity. Mouse peroxisome proliferator activated receptor gamma coactivator 1 (Pgcl) has been reported to enhance the expression of uncoupling protein-1, a key mediator of thermogenesis in brown adipose tissue (Puigserver et at, 1998, Cell 92, 829-839). We report here the characterization of the human PPARGC1 gene. PPARGC1 spans a genomic region of similar to 67 kb, is composed of 13 exons, and encodes a 91-kDa protein that exhibits 94% amino acid identity with the mouse ortholog. mRNA species, transcribed from the TATA-less promoter, are 6.4 and 5.3 kb in length due to utilization of two polyadenylation signals. Northern blotting revealed expression of both transcripts in heart, skeletal muscle, and kidney and to a lesser extent in liver, brain, and pancreas as well as in the perirenal adipose tissue of a pheochromocytoma patient. PPARGCI was mapped to chromosome 4p15.1, a region that has been associated with basal insulin levels in Pima Indians. Hence, PPARGC1 expression might influence insulin sensitivity as well as energy expenditure, thereby contributing to the development and pathophysiology of human obesity. (C) 1999 Academic Press.