PhD defence: Regulation of lipid metabolism in skeletal muscle

Insights from human cell culture and rodent models

Mette Landau Brabæk Christiansen

PhD thesis

Frontpage of PhD thesis

Understanding of how metabolism is regulated in the healthy individual is, despite extensive research, far from complete. Skeletal muscle represents 30-40% of total body mass and plays a major role in whole body homeostasis. In the present thesis regulation of lipid metabolism in skeletal muscle is addressed by use of different research models.

It is well established that sex differences exist in human skeletal muscle in vivo, both at a morphologic and metabolic level. However, the underlying cause of this sexual dimorphism remains uncertain. To address whether the sex difference in whole body metabolism originate from a sex difference intrinsic to the muscle cells, human muscle cell cultures were established from biopsies obtained from carefully matched male and female donors.

Triacylglycerol (TG) is transported in the blood bound to chylomicrons and VLDL and thereby delivered to the peripheral tissue for either storage or oxidation. Lipoprotein lipase (LPL) is the rate limiting enzyme for hydrolysis of TG and therefore represents an important regulator of delivery of fatty acids to the muscle cell. Energy demand increases several fold in exercising skeletal muscle compared with rest and in the present thesis, rodent exercise models was used as a way of increasing the activity of mLPL to elucidate the possible mechanisms involved in such regulation. In particular the roles of decreased muscle glycogen content and activation of AMPK in the regulation of mLPL activity in response to exercise were addressed.

2012, 134 pages, 100,- d.kr.,
ISBN 978 87 917 71 44 6

Time

Thursday 3 May 2012 at 13:00

Place

Auditorium 1, August Krogh building, Universitetsparken 13, Copenhagen

Opponents

Professor Ylva Hellsten (chair), Department of Exercise and Sport Sciences, University of Copenhagen, Denmark.

Professor Jørgen Jensen, Norwegian School of Sport Sciences, Norway.

Professor Arild C. Rustan, Muscle research group, Dept. Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Norway.

Supervisor

Professor Bente Kiens, Department of Exercise and Sport Sciences, Faculty of Science, University of Copenhagen, Denmark.