PhD defence: The impact of the intrauterine environment, exercise and physical inactivity on the skeletal muscle AMPK system and downstream targets

Brynjulf Mortensen

PhD thesis

Low birth weight (LBW) subjects are at increased risk of type 2 diabetes (T2D), and since physical activity/inactivity is one of the major determinants of T2D risk, challenges in both extreme ends of the physical activity spectrum may unmask defects in metabolism in LBW subjects.

During the last decade, accumulating evidence suggest that the AMP-activated protein kinase (AMPK) plays an important role in orchestrating several metabolic adaptations during/following exercise. Therefore, we hypothesized that LBW is associated with defects in muscle adaptations following bed rest, acute exercise and regular physical activity, evident by a birth weight-dependent response on skeletal muscle AMPK and downstream signalling after these interventions.

In summary the findings of this thesis suggest that when taking a cross-sectional approach, basal expression and activity of skeletal muscle AMPK is normal in LBW subjects. However, after performing a “diabetogenic” challenge such as bed rest, skeletal muscle insulin signalling is compromised in a birth weight-dependent manner, but probably via mechanisms independent of AMPK. The extent to which the bed rest-induced changes of insulin signaling contribute to the risk of T2D among LBW subjects remains to be determined.

In contrast to our hypothesis, we also conclude that LBW subjects show increased activation of skeletal muscle AMPK signaling during acute exercise, which might suggest a more sensitive AMPK system and/or a reduced ability to maintain cellular energy status during exercise in these subjects. These findings might prove relevant in future T2D prevention and treatment strategies in this population.

2012, 120 pages, 100,- d.kr.,
ISBN 978 87 917 71 45 3

Time

5 July 2012 at 13:00

Venue

Auditorium 1, August Krogh building, Universitetsparken 13, Copenhagen

Opponents

Associate professor Nicolas Caesar Petersen (chair), Department of Exercise and Sport Sciences, University of Copenhagen, Denmark.

Associate professor Niels Jessen, Aarhus University, Denmark.

Associate professor Susan E. Ozanne, University of Cambridge Metabolic Research Laboratories , Department of Clinical Biochemistry, Institute of Metabolic Science, Addenbrooke's Hospital, United Kingdom.

Supervisors

Professor Jørgen Wojtaszewski, Department of Exercise and Sport Sciences, University of Copenhagen, Denmark.

Professor Allan Vaag, Department of Endocrinology, Rigshospitalet, Denmark.