Progressive increase in human skeletal muscle AMPKα2 activity and ACC phosphorylation during exercise

Abstract

. Progressive increase in human skeletal muscle AMPK␣2 activity and ACC phosphorylation during exercise. Am J Physiol Endocrinol Metab 282: E688-E694, 2002; 10.1152/ajpendo.00101.2001.-The effect of prolonged moderate-intensity exercise on human skeletal muscle AMP-activated protein kinase (AMPK)␣1 and -␣2 activity and acetyl-CoA carboxylase (ACC␤) and neuronal nitric oxide synthase (nNOS) phosphorylation was investigated. Seven active healthy individuals cycled for 30 min at a workload requiring 62.8 Ϯ 1.3% of peak O2 consumption (V O2 peak) with muscle biopsies obtained from the vastus lateralis at rest and at 5 and 30 min of exercise. AMPK␣1 activity was not altered by exercise; however, AMPK␣2 activity was significantly (P Ͻ 0.05) elevated after 5 min (ϳ2-fold), and further elevated (P Ͻ 0.05) after 30 min (ϳ3-fold) of exercise. ACC␤ phosphorylation was increased (P Ͻ 0.05) after 5 min (ϳ18-fold compared with rest) and increased (P Ͻ 0.05) further after 30 min of exercise (ϳ36-fold compared with rest). Increases in AMPK␣2 activity were significantly correlated with both increases in ACC␤ phosphorylation and reductions in muscle glycogen content. Fat oxidation tended (P ϭ 0.058) to increase progressively during exercise. Muscle creatine phosphate was lower (P Ͻ 0.05), and muscle creatine, calculated free AMP, and free AMP-to-ATP ratio were higher (P Ͻ 0.05) at both 5 and 30 min of exercise compared with those at rest. At 30 min of exercise, the values of these metabolites were not significantly different from those at 5 min of exercise. Phosphorylation of nNOS was variable, and despite the mean doubling with exercise, statistically significance was not achieved (P ϭ 0.304). Western blots indicated that AMPK␣2 was associated with both nNOS and ACC␤ consistent with them both being substrates of AMPK␣2 in vivo. In conclusion, AMPK␣2 activity and ACC␤ phosphorylation increase progressively during moderate exercise at ϳ60% of V O2 peak in humans, with these responses more closely coupled to muscle glycogen content than muscle AMP/ ATP ratio. adenosine monophosphate-activated protein kinase; acetylcoenzyme A carboxylase-␤; neuronal nitric oxide synthase; prolonged exercise; humans AMP-ACTIVATED PROTEIN KINASE (AMPK) plays an important role in coordinating metabolism with a number of physiological processes (16,22). In rat skeletal muscle, activation of AMPK appears to lead to enhanced fat oxidation and glucose uptake (3,19,25). In transgenic mice expressing a dominant negative mutant of AMPK, there is impaired glucose uptake in response to both contraction and hypoxia (26). There are two isoforms of AMPK, AMPK␣1 and -␣2, expressed in skeletal muscle. Maximal sprint exercise [ϳ200% peak O 2 consumption (V O 2 peak )] over 30 s in humans causes a large increase in the calculated free AMP and free AMP-to-ATP ratio (AMP/ATP) (28) and activates both AMPK␣1 and -␣2 (6). AMPK␣1 is not activated during lower intensity exercise such as at 50 or 70% V O 2 peak , or after 5 min of exercise at 90% V O 2 peak after 55 min of cy...

Malonyl coenzyme A and the regulation of functional carnitine palmitoyltransferase-1 activity and fat oxidation in human skeletal muscle

“…Two of the studies reported no change in malonyl-CoA concentration (36,37), whereas a more recent study has reported a significant decrease in malonyl-CoA and ACC activity following exercise (38). The latter study appears to be consistent with studies reporting an increase in human muscle AMPK activity with exercise (39,40) and supports the notion that a decrease in malonyl-CoA during exercise allows for an increase in the rate of LCFA oxidation.…”

Effects of the nitric oxide donor, sodium nitroprusside, on resting leg glucose uptake in patients with type 2 diabetes

“…It has been postulated that NO and AMPK are part of the same signalling pathway. During exercise, AMPK phosphorylates nNOSμ in human skeletal muscle [46][47][48], while in rat skeletal muscle glucose uptake stimulated by the AMP analogue, 5-aminoimidazole-4-carboxamide ribonucleoside, which activates AMPK, can be blocked by an NOS inhibitor [49]. Further studies are required to clarify the relationship between NO and AMPK with regard to glucose uptake.…”

Long-term wheel running changes on sensorimotor activity and skeletal muscle in male and female mice of accelerated senescence

“…Physical exercise has recently emerged as a potential treatment for sarcopenia (Montero-Fernandez and Serra-Rexach 2013;Crane et al 2013), associated with benefits in musculoskeletal systems (Manabe et al 2013) and metabolic function (Stephens et al 2002). In mice, spontaneous wheel running may provide an excellent model to counteract the deterioration of motor skills and skeletal function associated with aging due to the fact that it is a voluntary rhythmic behavior, generally performed with a high degree of consistency and coordination.…”