A Preliminary Study On The Expression And Mechanism Of Palmitic Acid Affecting Musclin

Musclin is a bioactive factor secreted by skeletal muscle. Functionly，musclin inhibits the glucose uptake and the synthesis of glucogen in C2C12.Besides, the expression of musclin increased significantly in skeletal muscle ofobese and diabetes, and recent studies suggested that the increased expression ofmusclin may have some relationship with the disorder metabolism of glucoseand lipid in patients, but the mechanism under this phenomenon has beenunknown. Therefore, the objective of this work is to study the effects andmechanisms of palmitic acid on the expression of musclin in C2C12.In this work, Real-time PCR and Western Blot were adopted to examine theexpression of muslcin and endoplasmic reticulum (ER) stress response in C2C12myotubes under the treatment of palmitic acid. The results suggested thatpalmitic acid could change C2C12cellular morphology and lead to apoptosiseventually. Besides, palmitic acid could acce lerate the expression of musclin andstrengthen the stress reaction of ER in C2C12. In order to clarify therelationship between the expression of musclin and ER stress response, wetreated myotubes with ER stress inducer Tunicamycin (TM), and the resultsshowed the expression of musclin increased under the condition that ER stresswas strengthened, besides, we also applied ER stress inhibitor4-phenyl butyricacid (4-PBA) on C2C12to relieve the ER stress response induced by TM andpalmitic acid respectively, while the results suggested that the expression ofmusclin may decrease significantly when the ER stress was released. Finally, weadopted RNAi technique to knockdown PERK which is involoved in ER stresspathways, and we found that the effect of palmitic acid inducing the expressionof musclin gene was decreased under the condition that the PERK passway wasinhibited. The results incidated that PERK passway of ER stress actuallyparticipated in the regulation of musclin gene expression.In this study we found that palmitic acid inducing the expression of musclinincreased was regulated by ER stress in C2C12. Our study focused on theregulation mechanism of musclin expression may provide new insights for themetabolic syndrome treatment.