Originally cloned as PGC-1, PGC-1α is a cold-inducible protein, highly expressed in brown fat, that was initially shown to enhance the activity of the nuclear receptors PPAR-γ and TR on the uncoupling protein -1 promoter, and was subsequently shown to coactivate other members of the nuclear receptor superfamily. Studies have indicated a role for PGC1-α in hepatic gluconeogenesis. PGC-1 is expressed in a variety of tissues, principally metabolic tissues (heart, kidney, brown adipose tissue, muscle) and the central nervous system (olfactory bulb, cerebrum, hypothalamus). Variants of PGC-1 have been characterized in diabetes, diabetic retinopathy, hypertension and metabolic syndrome. Null deletion of PGC-1 results in defects in adaptive energy metabolism, muscle dysfunction, abnormal weight control and hepatic steatosis.