Cloning and expression of PPARγ and PGC-1α from the hibernating ground squirrel, Spermophilus tridecemlineatus

The peroxisome proliferator-activated receptor (PPAR) family of transcription factors play a key role in lipid metabolism and have been implicated in a number of disease states, most notably of which is obesity. Controlled regulation of lipid metabolism is a key ingredient for successful hibernation. Partial cDNA sequences for one of the PPAR proteins, PPARgamma and the PPARgamma coactivator (PGC-1alpha) have been cloned from the hibernating ground squirrel, Spermophilus tridecemlineatus and show differential regulation during hibernation at the mRNA level using relative RT-PCR and at the protein level via immunoblotting in brown adipose tissue (BAT), heart, skeletal muscle and white adipose tissue (WAT). The cDNA sequence for PGC-1alpha revealed a number of amino acid substitutions and two were worthy of note, one resulting in the loss of a potential protein kinase C ( PKC) site, while another resulted in the creation of a PKC site, suggesting that PKC may be important in regulating PGC-1alpha. RT-PCR revealed a near 2-fold up-regulation of PPARgamma in BAT and to a lesser extent (< 1.5-fold) in heart and WAT, while PGC-1alpha displayed significantly higher levels of expression in skeletal muscle during hibernation ( 3.1-fold, p < 0.005). The protein levels of PPARgamma were significantly increased in BAT and WAT ( 1.5 and 1.8-fold, respectively) while PGC-1alpha displayed significant changes in expression in heart ( 3.5-fold) and skeletal muscle ( 1.8-fold). Our current findings indicate a role for increased expression of PPARgamma and PGC-1alpha in hibernating animals.