Our previous study demonstrated that the Korean traditional medicine Gyeongshingangjeehwan (GGEx) inhibits obesity and insulin resistance in obese type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. We investigated whether GGEx may affect AMP-activated protein kinase α (AMPKα) since AMPKα activation is known to stimulate fatty acid oxidation in skeletal muscle of obese rodents. After OLETF rats were treated with GGEx, we studied the effects of GGEx on AMPKα and acetyl-CoA carboxylase (ACC) phosphorylation, and the expression of AMPKα, PPARα, and PPARα target genes. The effects of GGEx on mRNA expression of the above genes were also measured in C2C12 skeletal muscle cells. Administration of GGEx to OLETF rats for 8 weeks increased phosphorylation of AMPKα and ACC in skeletal muscle. GGEx also elevated skeletal muscle mRNA levels of AMPKα1 and AMPKα2 as well as PPARα and its target genes. Consistent with the in vivo data, similar activation of genes was observed in GGEx-treated

C2C12 cells. These results suggest that GGEx stimulates skeletal muscle AMPKα and PPARα activation, leading to alleviation of obesity and related disorders.

AMPK; C2C12; GGEx; Korean traditional medicine; Skeletal muscle; PPARα