Brock University, Department of Kinesiology, Centre for Bone and Muscle Health, St. Catharines, Canada.
Am J Physiol Regul Integr Comp Physiol. 2013 Apr 15;304(8):R644-50. doi: 10.1152/ajpregu.00418.2012. Epub 2013 Feb 13.
Evidence indicates that skeletal muscle lipid droplet-associated proteins (PLINs) regulate lipolysis through protein-protein interactions on the lipid droplet surface. In adipocytes, PLIN1 is thought to regulate lipolysis by directly interacting with comparative gene identification-58 (CGI-58), an activator of adipose triglyceride lipase (ATGL). Upon lipolytic stimulation, PLIN1 is phosphorylated, releasing CGI-58 to fully activate ATGL and initiate triglyceride breakdown. The absence of PLIN1 in skeletal muscle leads us to believe that other PLIN family members undertake this role. Our purpose was to examine interactions between PLIN2, PLIN3, and PLIN5, with ATGL and its coactivator CGI-58 at rest and following contraction. Isolated rat solei were incubated for 30 min at rest or during 30 min of intermittent tetanic stimulation [150-ms volleys at 60 Hz with a train rate of 20 tetani/min (25°C)] to maximally stimulate intramuscular lipid breakdown. Results show that the interaction between ATGL and CGI-58 increased 128% following contraction (P = 0.041). Further, ATGL interacts with PLIN2, PLIN3, and PLIN5 at rest and following contraction. The PLIN2-ATGL interaction decreased significantly by 21% following stimulation (P = 0.013). Both PLIN3 and PLIN5 coprecipitated with CGI-58 at rest and following contraction, while there was no detectable interaction between PLIN2 and CGI-58 in either condition. Therefore, our findings indicate that in skeletal muscle, during contraction-induced muscle lipolysis, ATGL and CGI-58 strongly associate and that the PLIN proteins work together to regulate lipolysis, in part, by preventing ATGL and CGI-58 interactions at rest.
有证据表明，骨骼肌脂滴相关蛋白（PLINs）通过在脂滴表面的蛋白-蛋白相互作用来调节脂肪分解。在脂肪细胞中，PLIN1 被认为通过直接与脂肪甘油三酯脂肪酶（ATGL）的激活剂比较基因鉴定-58（CGI-58）相互作用来调节脂肪分解。在脂肪分解刺激下，PLIN1 被磷酸化，释放 CGI-58 以完全激活 ATGL 并启动甘油三酯分解。骨骼肌中 PLIN1 的缺失使我们相信其他 PLIN 家族成员承担了这一角色。我们的目的是研究 PLIN2、PLIN3 和 PLIN5 与 ATGL 和其共激活剂 CGI-58 在休息和收缩时的相互作用。分离的大鼠比目鱼肌在休息时孵育 30 分钟或在 30 分钟的间歇性强直刺激下孵育（150-ms 波在 60 Hz 下，以 20 次抽搐/分钟的串率[25°C]刺激以最大程度地刺激肌内脂肪分解）。结果表明，收缩后 ATGL 和 CGI-58 的相互作用增加了 128%（P = 0.041）。此外，ATGL 在休息和收缩时与 PLIN2、PLIN3 和 PLIN5 相互作用。刺激后 PLIN2-ATGL 相互作用显著下降 21%（P = 0.013）。PLIN3 和 PLIN5 在休息和收缩时都与 CGI-58 共沉淀，而在任何条件下均未检测到 PLIN2 和 CGI-58 之间的相互作用。因此，我们的研究结果表明，在骨骼肌中，在收缩诱导的肌肉脂肪分解过程中，ATGL 和 CGI-58 强烈结合，PLIN 蛋白共同作用，部分通过在休息时防止 ATGL 和 CGI-58 相互作用来调节脂肪分解。
