PhD defence: Skeletal muscle and liver lipidomics and the regulation of FAT/CD36

Impact of high fat diet and exercise

Andreas Børsting Jordy

PhD thesis

Part I

Peripheral intramyocellular and intrahepatic lipid accumulation is associated with tissue-specific and whole body insulin resistance and, in the case of the liver non-alcoholic fatty liver disease. Studies show that regular exercise can reduce hepatic lipid content and enhance liver health. In high-fat diet induced obesity in mice, we observed an increased muscle and liver lipid content, analyzed by mass spectrometry, concomitant with decreased glucose tolerance. We observed that treadmill exercise-training in high-fat fed mice resulted in a reduction in the lipid content in the liver, but not in muscle, and in improved glucose tolerance. These data provide evidence that exercise-training may be a viable therapeutic intervention to prevent, or at least slow the progression of fatty liver that is associated with nutrient overload.

Part II

In skeletal muscle, multiple regulatory sites for fatty acid utilization exist; amongst these is fatty acid transport across the plasma membrane involving the fatty acid transporter FAT/CD36. Previous observations suggest that a permanent relocation of FAT/CD36 protein to the sarcolemma induces intracellular lipid accumulation, resulting in insulin resistance. Therefore, FAT/CD36 has been linked to insulin resistance. Whether increased FAT/CD36 protein at the sarcolemma is an early event in the development of decreased insulin sensitivity or whether it is a consequence of chronic oversupply of calories, increased plasma fatty acids or chronically altered metabolism is not known. We show here that a high-fat diet-induced decrease in insulin sensitivity in healthy humans is independent of a relocation or up-regulation of FAT/CD36 protein at the sarcolemma and that the accumulation of intramyocellular lipid content after a high-fat diet is independent of such an event.

2015, 115 pages,
ISBN 978 87 7611 870 9

Time

16 April 2015, 14:00

Place

Auditorium 1, August Krogh Building, Universitetsparken 13, DK-2100 Copenhagen.

Opponents 

Associate professor Nikolai Nordsborg (chair), Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark.

Professor Bret Goodpaster, Burnham Medical Research Institute, Orlando, USA.

Professor Arend Bonen, Guelph University, Ontario, Canada.

Supervisor

Professor Bente Kiens, Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark.