The role of the perilipin proteins in regulating intramuscular lipid metabolism: effect of exercise training

Physical inactivity is associated with dysregulation of intramuscular triglyceride (IMTG) metabolism leading to the accumulation of fatty acid metabolites and insulin resistance. This thesis aims to provide new information concerning the role of a subset of proteins associated with the metabolic regulation of IMTG-containing lipid droplets (LDs), known as the perilipin (PLIN) proteins, predominantly using immunofluorescence microscopy. Chapter 2 demonstrates that PLIN2-containing LDs are preferentially targeted for breakdown during moderate-intensity exercise in lean, sedentary males. Chapter 3 reveals that 6 months of endurance training (ET) in obese type 2 diabetes patients enhances PLIN2 content in type I fibres. Chapter 4 demonstrates that improvements in IMTG metabolism, including increased expression of PLIN2 and PLIN5, occur in response to both ET and sprint interval training (SIT) in lean, sedentary males. In Chapter 5 data is provided to show that RT also improves IMTG metabolism and insulin sensitivity in lean, sedentary males. Chapter 6 documents the effectiveness of a new constant-workload SIT protocol with regards to improving insulin sensitivity in obese individuals. In conclusion, this thesis generates novel data that contributes to our understanding of the underlying mechanisms that govern the relationship between IMTG metabolism and insulin sensitivity