The Effects of Aerobic Exercise Training and Insulin Resistance on Lipid Droplet Size and Perilipin Protein Association

Abstract

Skeletal muscle insulin resistance has been related to impaired glucose clearance, lipid accumulation, and chronic low-grade inflammation in type 2 diabetes mellitus (T2DM). Growing evidence suggests lipid droplet (LD) morphology and LD protein association may explain the pathology contributing to insulin resistance. In T2DM, surface proteins inhibit the utilization of large LDs, which can further impair insulin signaling and reduce skeletal muscle glucose uptake. Aerobic exercise (AEX) training has been shown to improve skeletal muscle oxidative capacity and trained skeletal muscle contains smaller LDs with a distribution of perilipin proteins favoring effective lipid utilization. The aims of this thesis study are to address gaps related to LD morphology and perilipin localization in human skeletal muscle through visual quantification and total muscle protein expression. The outcomes of this thesis will enhance the current understanding of how impaired glucose regulation influences lipid metabolism in skeletal muscle while highlighting the effects of physical activity on metabolic health. Lipid droplet volume decreased in response to training in oxidative type 1 skeletal muscle. There was an effect of training leading to an increase in perilipin 5 expression that was most prominent in T2DM group. Lipid droplet-associated Perilipin 2 did not change in response to training in T2DM individuals but was significantly reduced in normal glucose tolerance individuals. While Perilipin 2 and Perilipin 5 are two prominent proteins involved in lipid droplet regulation, they may serve different roles in the management of whole-body glucose regulation and skeletal muscle lipid morphology.