PLINs-mediated Organelle interactions: a key of exercise-mediated improvement of skeletal muscle lipid metabolism disorders

Zhiyuan LiuYungang Zhao^*

• Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, School of Exercise and Health, Tianjin University of Sport, Tianjin, China

Perilipins are essential structural proteins localized on the surface of lipid droplets, with perilipin 2, 3, and 5 exhibiting specific expression in skeletal muscle. Intramuscular lipids are predominantly stored within lipid droplets, tightly regulated by perilipins. Perilipin 3 primarily governs lipid droplet biogenesis, whereas Perilipin 2 and PLIN5 play critical roles in mediating lipolysis through lipid droplet-organelle interactions and in responding to exercise-induced signaling cascades. Acute exercise selectively depletes lipid droplets coated with Perilipin 2 and Perilipin 5 while inducing subcellular relocalization of perilipin proteins. In contrast, moderate-intensity continuous training and high-intensity interval training elicit adaptive alterations in skeletal muscle perilipins protein expression: Moderate-intensity continuous training significantly upregulates perilipin 2 and 5 expression, whereas high-intensity interval training specifically enhances perilipin5 expression, fostering enhanced physical interactions between lipid droplets and mitochondria, thereby mitigating ectopic lipid accumulation. This study elucidates the intricate regulatory mechanisms of perilipin-mediated organelle interactions under diverse exercise modalities and their contributions to optimizing skeletal muscle lipid metabolism, providing a robust theoretical framework for developing targeted exercise-based interventions and potential therapeutic targets for metabolic disorders.