AMP-activated Protein Kinase - Controversy

Controversy

A seemingly paradoxical role of AMPK occurs when we take a closer look at the energy-sensing enzyme in relation to exercise and long-term training. Similar to short-term acute training scale, long-term endurance training studies also reveal increases in oxidative metabolic enzymes and increases in GLUT-4, mitochondrial size and quantity, and an increased dependency on the oxidation of fatty acids; however, Winder et al. reported in 2002 that despite observing these increased oxidative biochemical adaptations to long-term endurance training (similar to those mentioned above), the AMPK response (activation of AMPK with the onset of exercise) to acute bouts of exercise decreased in red quadriceps (RQ) with training (3 – see Fig.1). Conversely, the study did not observe the same results in white quadriceps (WQ) and soleus (SOL) muscles that they did in RQ. The trained rats used for that endurance study ran on treadmills 5 days/wk in two 1-h sessions, morning and afternoon. The rats were also running up to 31m/min (grade 15%). Finally, following training, the rats were sacrificed either at rest or following 10 min. of exercise.

Because the AMPK response to exercise decreases with increased training duration, many questions arise that would challenge the AMPK role with respect to biochemical adaptations to exercise and endurance training. This is due in part to the marked increases in the biogenesis and upregulation of mitochondria, GLUT-4, UCP-3, Hexokinase II and other metabolic and mitochondrial enzymes despite decreases in AMPK activity with training. Questions also arise because skeletal muscle cells which express these decreases in AMPK activity in response to endurance training also seem to be maintaining an oxidative dependent approach to energy metabolism, which is likewise thought to be regulated to some extent by AMPK activity.

If the AMPK response to exercise is responsible in part for biochemical adaptations to training, how then can these adaptations to training be maintained if the AMPK response to exercise is being attenuated with training? It is hypothesized that these adaptive roles to training are maintained by AMPK activity and that the increases in AMPK activity in response to exercise in trained skeletal muscle have not yet been observed due to biochemical adaptations that the training itself stimulated in the muscle tissue to reduce the metabolic need for AMPK activation. In other words, AMPK will not become activated until it is "apparent" that the cell is in need of greater adaptation to exercise. Until energy stores (ATP) are depleted (ATP low + AMP high), AMPK will remain inactivated. Biochemical preparations for a high-intensity energy challenge must be exhausted before AMPK is to be activated in order to mediate further metabolic adaptations to exercise.