Hormone-sensitive lipase preferentially redistributes to lipid droplets associated with perilipin-5 in human skeletal muscle during moderate-intensity exercise.

Hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) control skeletal muscle lipolysis. ATGL is present on the surface of lipid droplets (LDs) containing intramuscular triglyceride (IMTG) in both the basal state and during exercise. HSL translocates to LD in ex vivo electrically stimulated rat skeletal muscle. Perilipin-2- and perilipin-5-associated lipid droplets (PLIN2+ and PLIN5+ LDs) are preferentially depleted during exercise in humans, indicating that these PLINs may control muscle lipolysis. We aimed to test the hypothesis that in human skeletal muscle in vivo HSL (but not ATGL) is redistributed to PLIN2+ and PLIN5+ LDs during moderate-intensity exercise. Muscle biopsies from 8 lean trained males (age 21 ± 1 years, BMI 22.6 ± 1.2 kg m-2 and V̇O2 peak 48.2 ± 5.0 ml min-1  kg-1 ) were obtained before and immediately following 60 min of cycling exercise at ∼59% V̇O2 peak . Cryosections were stained using antibodies targeting ATGL, HSL, PLIN2 and PLIN5. LDs were stained using BODIPY 493/503. Images were obtained using confocal immunofluorescence microscopy and object-based colocalisation analyses were performed. Following exercise, HSL colocalisation to LDs increased (P < 0.05), and was significantly greater to PLIN5+ LDs (+53%) than to PLIN5- LDs (+34%) (P < 0.05), while the increases in HSL colocalisation to PLIN2+ LDs (+16%) and PLIN2- LDs (+28%) were not significantly different. Following exercise, the fraction of LDs colocalised with ATGL (0.53 ± 0.04) did not significantly change (P < 0.05) and was not affected by PLIN association to the LDs. This study presents the first evidence of exercise-induced HSL redistribution to LDs in human skeletal muscle and identifies PLIN5 as a facilitator of this mechanism.