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

Abstract

Hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) control skeletal muscle lipolysis. ATGL is present on the surface of lipid droplets (LD) 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+ LD) are preferentially depleted during exercise in humans indicating 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+ LD during moderate-intensity exercise. Muscle biopsies from 8 lean trained males (age 21 ± 1 years, BMI 22.6 ± 1.2 kg.m⁻² and V̇o_2peak 48.2 ± 5.0 ml.min⁻¹.kg⁻¹) were obtained before and immediately following 60 min of cycling exercise at ∼59% V̇o_2peak. Cryosections were stained using antibodies targeting ATGL, HSL, PLIN2 and PLIN5. LD 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 LD increased (P < 0.05), and was significantly larger to PLIN5+LD (+53%) than to PLIN5-LD (+34%) (P < 0.05), while the increases in HSL colocalisation to PLIN2+LD (+16%) and PLIN2-LD (+28%) were not significantly different. Following exercise the fraction of LD colocalised with ATGL (0.53 ± 0.04) did not significantly change (P < 0.05) and was not affected by PLIN association to the LD. This study presents the first evidence of exercise-induced HSL redistribution to LD in human skeletal muscle and identifies PLIN5 as a facilitator of this mechanism.

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