Characterization of the human, mouse and rat PGC1β (peroxisome-proliferator-activated receptor-γ co-activator 1β) gene in vitro and in vivo

PGC1alpha is a co-activator involved in adaptive thermogenesis, fatty-acid oxidation and gluconeogenesis. We describe the identification of several isoforms of a new human PGC1alpha homologue, cloned independently and named PGC1beta. The human PGC1beta gene is localized to chromosome 5, has 13 exons and spans more than 78 kb. Two different 5' and 3' ends due to differential splicing were identified by rapid amplification of cDNA ends PCR and screening of human cDNA libraries. We show that PGC1beta variants in humans, mice and rats are expressed predominantly in heart, brown adipose tissue, brain and skeletal muscle. PGC1beta expression, unlike PGC1alpha, is not up-regulated in brown adipose tissue in response to cold or obesity. Fasting experiments showed that PGC1alpha, but not PGC1beta, is induced in liver and this suggests that only PGC1alpha is involved in the hepatic gluconeogenesis. No changes in PGC1beta gene expression were observed associated with exercise. Human PGC1beta-1a and -2a isoforms localized to the cell nucleus and, specifically, the isoform PGC1beta-1a co-activated peroxisome-proliferator-activated receptor-gamma, -alpha and the thyroid hormone receptor beta1. Finally, we show that ectopic expression PGC1beta leads to increased mitochondrial number and basal oxygen consumption. These results suggest that PGC1beta may play a role in constitutive adrenergic-independent mitochondrial biogenesis.