Dissociation of AMPK activity and ACCβ phosphorylation in human muscle during prolonged exercise

Abstract

During prolonged, low intensity exercise, the type of substrate utilized varies with time. If 5 ′AMP-activated protein kinase (AMPK) regulates muscle metabolism during exercise, signaling through AMPK would be expected to change in concordance with changes in substrate utilization. Six healthy, young males cycled (∼45% VO 2peak) until exhaustion (∼3.5 h). During exercise, leg glucose uptake and rate of glycogenolysis gradually decreased whereas free fatty acid uptake gradually increased. In the thigh muscle, the α AMPK subunits became progressively more phosphorylated on Thr 172 during exercise eliciting a parallel increase in α2 but not α1 AMPK activity. In contrast, after 1 h of exercise, Ser 221 phosphorylation of acetyl-CoA carboxylase-β (ACCβ) peaked at 1 h of exercise and returned to resting levels at exhaustion. Protein expression of α2 AMPK, α1 AMPK or ACCβ did not change with time. These data suggest that AMPK signaling is not a key regulatory system of muscle substrate combustion during prolonged exercise and that marked activation of AMPK via phosphorylation is not sufficient to maintain an elevated ACC β Ser 221 phosphorylation during prolonged exercise.