Lunasin對C2C12肌小管細胞其發炎反應與葡萄糖利用之探討 The effects of lunasin on inflammatory response and glucose utilization in C2C12 myotubes

Date
2021
Authors
黃靖雅
Huang, Ching-Ya
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
摘要 肥胖為罹患心血管疾病、癌症、胰島素阻抗及第二型糖尿病的主要危險因子,並在近年來快速增加成為全球的流行病。肥胖會導致體內脂肪激素及游離脂肪酸異常增加,而脂肪激素、游離脂肪酸與及其代謝衍生物會干擾胰島素作用,進而造成胰島素阻抗。種子胜肽lunasin具有抗癌、抗發炎、抗氧化、調節膽固醇以及調節免疫功能等生理功能。本研究目的為探討lunasin處理對肥胖模式下C2C12小鼠肌小管細胞發炎反應和葡萄糖利用之影響。實驗中,將C2C12小鼠肌小管細胞以棕櫚酸 (palmitic acid, PA) 或adipocyte conditioned medium (Ad-CM) 刺激,引發胰島素阻抗以及模擬肥胖微環境,再給予lunasin處理。結果顯示,lunasin的介入不影響C2C12小鼠肌小管細胞存活率,於發炎模式中,lunasin處理能夠顯著降低自然狀態下能單核細胞趨化蛋白-1 (monocyte chemoattractant protein-1, MCP-1;CCL2) 基因表現;在PA誘導的胰島素阻抗模式中,顯著降低腫瘤壞死因子-α (tumor necrosis factor α, TNF-α) 基因表現,及MCP-1和介白素-6 (interleukin-6, IL-6) 的分泌量。在氧化壓力及細胞活性方面,lunasin的介入能夠降低胰島素阻抗及肥胖模式下所刺激產生的活性氧 (reactive oxygen species, ROS),並增加健康細胞比例。於葡萄糖代謝方面,進行了免疫螢光染色、葡萄糖攝入及測量培養基中葡萄糖量來表示胰島素敏感性,實驗結果發現lunasin的介入能夠增加葡萄糖轉運蛋白4 (glucose transporter-4, GLUT4) 之蛋白表現、改善葡萄糖攝入與胰島素敏感性,並顯著增加在PA誘導的胰島素阻抗模式中的肝醣貯存量。綜合上述,lunasin可能減緩肥胖模式下肌肉細胞發炎反應及調節葡萄糖利用,進而改善胰島素阻抗。目前對於lunasin在肥胖模式下藉由何種途徑調控發炎及葡萄糖代謝還尚未清楚,值得更進一步的探討。
Abstract Obesity is the main risk factor for cardiovascular disease, cancer, insulin resistance and type 2 diabetes. It has rapidly increased in recent years and has become a global epidemic. Abnormal raise of free fatty acids (FFAs) in the circulating in obesity is a critical issue related to insulin resistance. FFAs and its derived metabolites interfere with the insulin action in skeletal muscle. Lunasin, a peptide with 43 amino acid residues, was originally isolated from soybeans, and hasbeen demonstrated many biological activities including anti-inflammatory, anti-cancer, anti-oxidation and immune regulation. The aim of this study, we examined the effect of lunasin regulates obesity-related inflammation in C2C12 myotubes. Palmitic acid (PA) and adipocyte-conditioned medium (Ad-CM) were used to mimic the obesity-related microenvironment in our experiment. The results showed that lunasin didn’t affect cell viability in C2C12 myotubes. Lunasin treatment inhibited tumor necrosis factor-α (TNF-α) mRNA expression and chemoattractant protein-1 (MCP-1), and interleukin 6 (IL-6) proteins secretion in the PA condition. Lunasin can also reduce the expression of MCP-1 and IL-6 genes in spontaneous. In addition, lunasin decreased ROS levels while increased healthy cells under PA and H2O2 challenges. In glucose utilization, lunasin treatment can improve GLUT4, glucose uptake and insulin sensitivity. Moreover, glycogen storage is significantly increased in PA-induced C2C12 myotubes. In conclusions, lunasin suppressed obesity-related inflammation, oxidative stress andcell viability in C2C12 myotubes. Furthermore, it may increase GLUT4 to improve glucose uptake and insulin sensitivity. By reducing inflammation and regulating the utilization of glucose, insulin resistance is improved in skeletal muscle cells. However, the signaling pathway of lunasin regulates inflammation and glucose homeostasis in obesity need further study.
Description
Keywords
Lunasin, C2C12, 肥胖, 抗發炎, 胰島素阻抗, Lunasin, C2C12, obesity, Anti-inflammatory, insulin resistance
Citation
Collections