Emerging Roles of AMP-Activated Protein Kinase: The Role of AMPK in Regulatin of Substrate Utilisation During and After Acute Exercise, Adipose Tissue Metabolism During Weight Loss, and Autophagy in Skeletal Muscle During Acute Exercise

Publikation: Bog/antologi/afhandling/rapportPh.d.-afhandlingForskning

The cellular energy sensor AMP-activated protein kinase (AMPK) is activated, when the energy balance of the cell decreases. AMPK has been proposed to regulate multiple metabolic processes. However, much of the evidence for these general effects of AMPK relies on investigations in cell systems or has focused on specific physiological situations and tissues.
The present PhD thesis has addressed the role of AMPK in regulation of: 1) substrate utilisation during and in recovery from exercise, 2) adipose tissue metabolism during weight loss, and 3) autophagy in skeletal muscle during exercise. The findings have been published in three papers. In addition, the thesis comprises unpublished work. Our data show that AMPK in skeletal
muscle seems not to be required for the regulation of fatty acid (FA) and glucose oxidation during exercise. Instead, the AMPK activation occurring in skeletal muscle during exercise appears to inhibit pyruvate dehydrogenase (PDH) activity by an immediate up-regulation of pyruvate dehydrogenase kinase 4 (PDK4) protein content. Consequently, this may inhibit glucose oxidation and thereby generate conditions for increased FA oxidation and glycogen resynthesis in skeletal muscle during post exercise recovery. AMPK seems therefore to play a
role in substrate selection post exercise. In adipose tissue, basal AMPK activity is decreased in obese and insulin resistant states and is increased in human adipose tissue during weight loss. The underlying mechanisms for increased
AMPK activity in adipose tissue after weight loss are not clear, but could be due to an increase in circulating adiponectin, increased lipolysis-driven energy demanding re-esterification and/or decreased insulin-mediated AMPK inhibition. Increased AMPK activity in adipose tissue during weight loss could be of importance for prioritising energy dissipation, inhibition of lipid storage
pathways and regulation of mitochondrial and metabolic proteins, but this needs further investigations. In addition, we provide evidence that AMPK is regulating autophagic signalling in skeletal muscle. Thus, in skeletal muscle AMPK is an upstream kinase phosphorylating Unc51 like kinase 1 (ULK1) at Ser555, but this interaction per se seems not to be sufficient to change the autophagosome content. It cannot be excluded whether the AMPK-ULK1 association is important and necessary for regulation of autophagy and autophagosome biogenesis in skeletal muscle during exercise, but AMPK activation alone appears not to be a sufficient stimulus.
ForlagDepartment of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen
Antal sider138
StatusUdgivet - 2016

ID: 164211468