Regulation of energy metabolism in skeletal muscle cells by PPAR activation, in vitro exercise and perilipin 2 ablation Studies in human and mice myotubes

.............................................................................................................................. 4 INTRODUCTION ...................................................................................................................... 6 Energy metabolism in skeletal muscle ................................................................................... 6 Dynamics of skeletal muscle lipid pools ............................................................................ 9 Metabolic flexibility of skeletal muscle ............................................................................ 10 Skeletal muscle fiber types ............................................................................................... 11 Role of peroxisome proliferator-activated receptors (PPARs) in energy metabolism in skeletal muscle ...................................................................................................................... 12 Peroxisome proliferator-activated receptor / ................................................................. 12 Exercise and energy metabolism in skeletal muscle ............................................................ 14 Skeletal muscle as a secretory organ................................................................................. 18 Insulin resistance, obesity and type 2 diabetes ..................................................................... 19 AIMS OF PRESENT STUDIES .............................................................................................. 22 SUMMARY OF PAPERS ....................................................................................................... 23 Paper I ................................................................................................................................... 23 Paper II ................................................................................................................................. 25 Paper III ................................................................................................................................ 27 Paper IV ................................................................................................................................ 29 METHODOLOGICAL CONSIDERATIONS ......................................................................... 31 Cultured skeletal muscle cells as an in vitro model .............................................................. 31 Donor characteristics ............................................................................................................ 33 Methods used to measure energy metabolism in cultured skeletal muscle cells .................. 35 DISCUSSION AND CONCLUSIONS .................................................................................... 37 Oxidative capacity and metabolic flexibility ........................................................................ 37 Fast-to-slow transformations in skeletal muscles ................................................................. 41 Lipid storage and turnover .................................................................................................... 42 Effects on insulin sensitivity ................................................................................................. 45 Final considerations .............................................................................................................. 46 REFERENCES ......................................................................................................................... 48