Summary: | 碩士 === 國防醫學院 === 生物及解剖學研究所 === 98 === Trimucrin, a disintegrin protein with anti-platelet aggregation activity, isolated from snake venom of Trimeresurus mucrosqumatus ( Taiwan habu ) gene bank, was expressed in Yarrowia lipolytica. The expressed protein demonstrated not only with anti-platelet aggregation activity in vitro but also with body weight-reduction in vivo. In searching for the weight reduction mechanisms, we found that trimucrin reduced the body weight by two mechanisms: (1) decrease food intake; (2) promote lipolysis in adipocytes. Studies have indicated that trimucrin-induced lipolysis is through PKA, ERK and HSL. For many decades, scientist considered the only enzyme for the hydrolysis of triglyceride is HSL. However, the nonobse phenotype of HSL knock-out mice and the accumulation of diglyceride (DG) in their adipose tissue suggested presence of additional lipase in adipose tissue that preferentially hydrolysis triglyceride(TG). In 2004, a novel TG hydrolase named ATGL was demonstrated, and several evidences suggested that ATGL plays an important role in lipolysis. The purpose of this study is to identify trimucrin-induced lipolysis through ATGL. After trimucrin stimulation, ATGL protein expression was decreased. Previous work suggested that CGI-58, a protein activator of ATGL, interact with ATGL during stimulated lipolysis. Our results showed that trmucrin didn’t increase CGI-58-binding ATGL. Taken together, trimucrin stimulated 3T3-L1 lipolysis could be through HSL pathway, but not through ATGL pathway.
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