Regulation of skeletal muscle lipolysis
PhD thesis by Thomas Junker Alsted
2010, 121 pages, DKR 100,-
ISBN: 978 87 917 71 279
Mobilization of fatty acids from stored triacylglycerol (TG) in skeletal muscle (intramyocellular triacylglycerol, IMTG) requires activity of lipases. In skeletal muscle, hormone-sensitive lipase (HSL) has generally been accepted to be the primary lipase responsible for hydrolysis of IMTG, but recently adipose triglyceride lipase (ATGL) was identified as a TG-specific lipase in various rodent tissues. In the present thesis, the importance of ATGL for lipolysis of IMTG in human and rat skeletal muscle was addressed.
Before the initiation of the present thesis, the knowledge of ATGL in skeletal muscle was scarce and therefore the majority of work with the present thesis was to optimize methods for measuring ATGL activity and IMTG degradation in rodent skeletal muscle. Results from an activity assay which enable differentiation between ATGL and HSL activities, demonstrated that ATGL is present in human skeletal muscle. Furthermore, the effect of a period of endurance exercise training on lipase protein expression and phosphorylations was investigated in healthy young male subjects. Using an ex vivo incubation model on rat soleus muscles with and without the presence of a pharmacological inhibitor of HSL, it was investigated whether HSL is the only TG-lipase that is activated during contractions, as previously suggested, or if ATGL contributes to lipolysis of IMTG.
The results of the present thesis indicate that ATGL in addition to HSL is important for lipolysis of IMTG in skeletal muscle. In addition to the experimental data, the present thesis provides a review of the literature describing the regulation of TG-lipases in skeletal muscle and adipose tissue. Furthermore, a number of molecular mechanisms which may be involved in regulation of ATGL activity and a potential role of TG-lipases as targets for prevention and treatment of insulin resistance are discussed.
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