Cardiff Metropolitan University
900 - Hannah Moir.pdf (1.86 MB)

Expression and activation of the 5'AMP-activated protein kinase (AMPK) in exercising and energy-depleted cells: an investigation into the molecular basis underpinning exercise-induced immunosuppression

Download (1.86 MB)
posted on 2022-10-14, 14:14 authored by Hannah Moir


High-intensity exercise has been associated with an increased susceptibility to illness and

infections, yet the underlying metabolic mechanism underpinning the onset of a suppressed

immune system has yet to be determined. In view of the importance of preventing

overtraining and the associated impact on health and sporting performance, the aim of the

current thesis was to determine the role of 5'AMP-activated Protein Kinase (AMPK) in the

maintenance of cellular energy within immune cells, and thus its influence on the

functional abilities of immune cells.

Two experimental approaches were employed: in vitro studies involving cultured

monocytic monomac6 cells to confirm the importance of AMPK in maintaining correct

cellular energy status, and in vivo studies to determine the effects of acute bouts of highintensity

exercise of ~70% VO2max in various exercise modes (cycling, running and

rowing), on AMPK activation within human mononuclear cells, and several markers of

global immune function. Also, an 8-week training programme was employed to investigate

the chronic effects of high-intensity exercise on mononuclear cell AMPK activation, and

markers of global immune function.

In vitro data confirmed AMPKα1 isoform expression in monocytes, which is activated by

hypoxia-induced decreases in cellular ATP levels (mimicked by in vitro oligomycin

treatment) to phosphorylate inducible phosphofructokinase-2, and activate anaerobic

glycolysis to replenish cellular energy stores. In contrast, bouts of high intensity exercise

(~70% VO2max for 45 minutes) brought about transient dephosphorylation of AMPK for

~1 hour post-exercise, which correlated to transient decreases in immune function

(detected as decreased salivary IgA and suppressed cytokine release). Dephosphorylation

of AMPK occurred via an AMP:ATP-independent mechanism, and coincided with a

decrease in intracellular levels of reactive oxygen species. Importantly, AMPK inactivation

lessened in extent in mononuclear cells following an 8-week training programme.

In conclusion, these studies detail the potential involvement of AMPK inactivation, and the

consequent disruptions in cellular energy homeostasis in mononuclear cells following an

acute bout of exercise. Longitudinal data suggests improvements by chronic training

adaptations, but in general, propose a role that AMPK inactivation may repress immune

cell function.



  • School of Sport and Health Sciences

Qualification level

  • Doctoral

Qualification name

  • PhD

Publication year


Usage metrics

    Cardiff Met Theses Collection


    Ref. manager