The effects of PDK4 inhibition on AMPK protein levels and PGC-1α gene expression following endurance training in skeletal muscle of Wistar rats

Abstract

There are regulatory networks in cells which surveil the physiological and environmental states. These cellular regulations are conducted through gene expression modulation. Skeletal muscle is able to adapt shortly and produce ATP at different conditions. AMPK (AMP-activated protein kinase) and PGC-1α (peroxisome proliferator-activated receptor-gamma coactivator-1alpha) are important regulators of cellular energy homeostasis. We designed this study to examine the effects of interactions between endurance training­ and PDK4 (pyruvate dehydrogenase kinase 4) inhibition on AMPK and PGC-1α expression in rat skeletal muscle. Thirty-two male Wistar rats were randomly selected and divided into 4 groups (n = 8); Group 1 control which did not receive any treatment, Group 2 received dichloroacetic acid (DCA) (150 mg/kg/day), Group 3 (endurance training group), Group 4 which received DCA and performed endurance training. AMPK protein expression, PDK4 and PGC-1α gene expression were measured by western blotting and real-time PCR, respectively. Our data showed that PDK4 inhibition caused AMPK protein elevation. Endurance training­ (group 2) and PDK4 inhibition (group 4) induce significant enhancement of PGC-1α gene expression compared to control group. The group which received DCA showed significant elevation of PDK4 gene expression compared to control group (P = 0.001), also other two groups (groups 2 & 3) showed significant elevation of PDK4 gene expression compared to control (P = 0.006). It seems that the combination of endurance training and PDK4 inhibition by up-regulation of PGC-1α expression, effectively improves energy state and performance in skeletal muscle.

Keywords

• AMPK
• dichloroacetic acid
• endurance training
• PGC-1α
• pyruvate dehydrogenase kinase 4