As mentioned above, when athletes train at intensities above the lactate threshold a dramatic increase in epinephrine is seen [
53]. Epinephrine also increases when athletes exercise for long periods without consuming carbohydrates or when they exercise in a glycogen-depleted state [
54]. Epinephrine has many functions in the body that allow athletes to exercise at high intensities. It also plays an important role in the adaptation to exercise through the activation of PGC-1α2 transcription [
10]. In mice, simply injecting a drug that mimics the effects of epinephrine increases the transcription of PGC-1α2, whereas mice lacking functional β-receptors do not experience an increase in PGC-1α2 transcription following exercise [
55]. This suggests that epinephrine is important in the molecular adaptation to endurance exercise. Interestingly, β-agonists activate only the alternative promoter that is seen with exercise in muscle and brown fat [
10,
56]. As with CamK, epinephrine does this by increasing CREB activity [
56], this time through its second messengers cAMP and protein kinase A. The result of repeated intermittent rises in epinephrine is an increase in mitochondria and the formation of new blood vessels in muscle [
10]. In contrast to this view, Robinson et al. [
57] did not see an increase in PGC-1α expression or mitochondrial protein synthesis within the first 5 h after infusing the β-agonist isoproterenol. However, it is important to note that isoproterenol is not a specific β-agonist (it also activates α-adrenergic receptors and this can antagonize β-activation [
58]). Therefore, whether catecholamines can acutely regulate PGC-1α in humans remains to be determined. However, the animal data are strong enough to encourage athletes to train in ways that increase epinephrine levels, such as in the heat [
59], in glycogen depletion [
54], or at high intensities [
53].