Cellular localization and associations of the major lipolytic proteins in human skeletal muscle at rest and during exercise

• Published in: PloS one 2014-07, Vol.9 (7), p.e103062-e103062
• Main Authors: Mason, Rachael R, Meex, Ruth C R, Russell, Aaron P, Canny, Benedict J, Watt, Matthew J
• Format: Article
• Language: English
• Subjects: 1-Acylglycerol-3-Phosphate O-Acyltransferase - analysis; 1-Acylglycerol-3-Phosphate O-Acyltransferase - metabolism; Adipocytes; Adult; Biology; Biology and Life Sciences; Cells, Cultured; Endocrinology; Exercise; Exercise - physiology; Fatty acids; Gene expression; Humans; Identification; Intracellular Signaling Peptides and Proteins - analysis; Intracellular Signaling Peptides and Proteins - metabolism; Kinases; Laboratories; Lipase; Lipase - analysis; Lipase - metabolism; Lipids; Lipolysis; Localization; Medicine and Health Sciences; Metabolism; Mitochondria; Mitochondrial DNA; Muscle Fibers, Skeletal - chemistry; Muscle Fibers, Skeletal - physiology; Muscle Fibers, Skeletal - ultrastructure; Muscle Proteins - analysis; Muscle Proteins - metabolism; Muscle, Skeletal - physiology; Muscle, Skeletal - ultrastructure; Muscles; Musculoskeletal system; Myocytes; Nutrition; Perilipin-5; Pharmacology; Phosphorylation; Physical fitness; Physiology; Post-translation; Proteins; Regulators; Research and Analysis Methods; Rest - physiology; Skeletal muscle; Studies; Triglycerides; Workloads; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0103062

Lipolysis involves the sequential breakdown of fatty acids from triacylglycerol and is increased during energy stress such as exercise. Adipose triglyceride lipase (ATGL) is a key regulator of skeletal muscle lipolysis and perilipin (PLIN) 5 is postulated to be an important regulator of ATGL action of muscle lipolysis. Hence, we hypothesized that non-genomic regulation such as cellular localization and the interaction of these key proteins modulate muscle lipolysis during exercise. PLIN5, ATGL and CGI-58 were highly (>60%) colocated with Oil Red O (ORO) stained lipid droplets. PLIN5 was significantly colocated with ATGL, mitochondria and CGI-58, indicating a close association between the key lipolytic effectors in resting skeletal muscle. The colocation of the lipolytic proteins, their independent association with ORO and the PLIN5/ORO colocation were not altered after 60 min of moderate intensity exercise. Further experiments in cultured human myocytes showed that PLIN5 colocation with ORO or mitochondria is unaffected by pharmacological activation of lipolytic pathways. Together, these data suggest that the major lipolytic proteins are highly expressed at the lipid droplet and colocate in resting skeletal muscle, that their localization and interactions appear to remain unchanged during prolonged exercise, and, accordingly, that other post-translational mechanisms are likely regulators of skeletal muscle lipolysis.