| Summary: | 碩士 === 國防醫學院 === 生理學研究所 === 104 === Raspberry ketone(RK) is a natural phenolic compound of the red raspberry. This compound has recently been reported to possess an antiobesity effect, which prevents high fat diet-induced obesity and increases fatty acid metabolism in animal model and cell line studies. To exam how RK regulates adipocyte differentiation was our first aim of this study. The results showed that RK inhibits adipogenesis and fat accumulation by downregulating the protein expression of adipogenic transcription factors: PPARγ、C/EBPα and lipogenic-related proteins: FAS and FABP4. In addition, adipocyte differentiation requires multiple steps to remove intracellular compound although the exact mechanisms are still unknown.
Autophagy, the process of cellular self-eating, has been recognized an critical pathway for cytosolic compound degradation to maintain cell survival. Activating autophagy enhances specific organelles or proteins are removed through the autophagy degradation system, which is essential process for preadipocyte storages oil droplets then turn into mature adipocyte. Downregulating autophagy via regulating autophagy-related proteins expression maybe a make sense way to impair adipogenesis. Therefore, we interested to investigate whether RK suppress adipogenesis and fat accumulation by modulating autophagic process. The 3T3-L1 differentiated cells are treated with 300μM RK during adipogenesis. The results showed that RK significantly decreases positive autophagy markers LC3II and Atg5-12 proteins expression, meanwhile, negative autophagy marker p62 protein expression was increased after RK treatment. In previous studies have regarded that mTOR is critical positive autophagy marker. Here, we showed that RK significantly increases mTOR activation, however, inhibits p-ULK1 and ULK1 protein expression. Based on the above results, we suggested that RK downregulates autophagy activation by modulating mTOR—ULK1 signaling pathway. In addition, recent studies indicated that AMPK and SIRT1 are mTOR upstream regulators. Interestingly, our results showed that RK can inhibits AMPK phosphorylation and decreases SIRT1 protein expression. These results further supported the hypothesis that RK suppress adipogenesis and fat accumulation via decreasing autophagy activation of this study.
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