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Beschreibung

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (UniProt: O70343, also known as PGC-1-alpha, PPAR-gamma coactivator 1-alpha, PPARGC-1-alpha) is encoded by the Ppargc1a (also known as Pgc1, Pgc1a, Ppargc1) gene (Gene ID: 19017) in murine species. PGC-1 alpha is a member of a family of transcription coactivators that plays a central role in the regulation of cellular energy metabolism. It is a homooligomeric transcriptional coactivator for steroid receptors and nuclear receptors that greatly increases the transcriptional activity of PPARG and thyroid hormone receptor on the uncoupling protein promoter. It is expressed in muscles, liver, kidney, brown adipose tissue, heart, and brain. It can regulate key mitochondrial genes that contribute to the program of adaptive thermogenesis and is also reported to play an essential role in metabolic reprogramming in response to dietary availability through coordination of the expression of a wide array of genes involved in glucose and fatty acid metabolism. PGC-1 alpha is known to induce the expression of PPARGC1- and ESRR-induced regulator, muscle 1 (PERM1) in the skeletal muscle in an estrogen-related receptors, -alpha (ESRRA)-dependent manner. PGC-1 alpha is significantly induced in brown adipose tissue and skeletal muscle by exposure to cold and is also shown to be up-regulated in brown adipose tissue of obese leptin-deficient (ob/ob) and leptin-unresponsive (db/db) mice. PGC-1 alpha is also required for oscillatory expression of clock genes, such as ARNTL/BMAL1 and NR1D1, through the co-activation of RORA and RORC, and metabolic genes, such as PDK4 and PEPCK.