Trimucrin-stimulated Lipolysis in Lipid Accumulated 3T3-L1 Adipocytes

• Main Authors: Yu-chieh Wang, 王佑傑
• Other Authors: Yaw-Wen Guo
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/40956518069244523732

碩士 === 國防醫學院 === 生物及解剖學研究所 === 94 === Trimucrin, a disintegrin protein with potential anti-platelet aggregation activity, was isolated from snake venom of Trimeresurus mucrosqumatus (Taiwan habu) and successfully expressed in Pichia pastoris. The expressed protein demonstrated not only with anti-platelet aggregation activity in vitro but also with body weight-reduction effect in vivo. In the weight-reduction assay, trimucrin reduced the body weight of rats effectively in reverse to their body weight. Physiologically, in overweighed animals, their adipose tissues show not only hyperplasia but also hypertrophy in cellular characteristic and the changes of adipose tissue were highly associated with integrin receptor differentiation. In this study, 3T3-L1 adipocyte cells could provide a useful cellular model in the investigation of molecular mechanisms. In this proposal, we examined the molecular mechanism of trimucrin on lipolysis in sterol ester (SE)-induced lipid accumulated 3T3-L1 cells and to determine the possible signaling mechanism involved. Our results demonstrated that the trimucrin treated 3T3-L1 cells resulted in the reduction in lipid droplets which were characterized by the reduction of lipid accumulation, the increase of HSL activity and the release of glycerol into the culture cell supernatant. Our study also strongly suggested that the trimucrin treated cells induced a lipolysis effect in 3T3-L1 cells. However, this Trimucrin-induced lipolysis effect might be induced through the integrin receptors binding. And these phenomena were highly supported by the complete inhibition of an integrin antagonist GRGDTP in this study. In addition, the integrin binding signaling pathway were confirmed by the downstream PKA and ERK pathway by specific inhibitors of protein kinase A (PKA) and extracellular signal-regulated kinase (ERK).