肥胖是目前全球所重視的議題，主要是由於飲食生活習慣的改變，導致肥胖人口比例逐漸增加。而現今很多的文獻也指出，肥胖和許多疾病有所關聯，例如是第二型糖尿病、心血管疾病等。肥胖是由於過多脂肪組織累積而成，因此研究脂肪細胞的分化有助於了解其參予在代謝疾病上的機制。先前的研究指出，脂肪細胞的分化會受到一連串的訊息傳遞分子所調控的，例如一些轉錄因子PPARγ 和 C/EBP 的成員等，而這些轉錄因子是透過胰島素訊息傳遞路徑所調控(已知胰島素訊息傳遞路徑對於脂肪細胞分化扮演重要的角色)。Eps8為EGFR的受質，且也是Src的受質，文獻指出Eps8會受到EGFR、Src調控其磷酸化以及表達量。進一步的研究也指出過度表達Eps8會回饋調控Src的活性，同時在2005年的文獻也指出，Src family tyrosine kinases對於脂肪細胞油滴的累積是非常重要的，所以引發我們想要去探討其受質Eps8是否也參與在脂肪細胞分化以及油滴累積的過程中。在我的實驗中，首先觀察Eps8在分化過程中表達的情形，發現到在分化初期會隨著刺激的時間增加，表達量隨之上升，而進入分化晚期表達量則逐漸減少，接著建立Eps8 knock down的細胞株(3T3-L1)，並使其誘導分化觀察其脂肪細胞分化的情形，結果我們發現在抑制Eps8表達量的情況下，同時也會抑制脂肪細胞的分化以及油滴的累積；更進一步去分析與脂肪細胞分化相關的基因，例如是PPARγ、lipoprotein lipase、fatty acid synthase(脂肪酸合成酶)，則發現到PPARγ以及fatty acid synthase在刺激後都會受到抑制，所以我們接著去探討Eps8是如何影響胰島素調控PPARγ以及脂肪酸合成酶。結果我們發現在抑制Eps8表達量的情形下，因胰島素刺激而活化的ERK、STAT3其活性會降低，顯示出Eps8參與在胰島素調控PPARγ以及脂肪酸合成酶的表達，可能是透過ERK/STAT3的路徑。根據上述的實驗結果顯示Eps8對於脂肪細胞的分化以及胰島素調控PPARγ以及脂肪酸合成酶的表達是相當重要的。

Obesity becomes a major health concern worldwide due to its strong association with type 2 diabetes and cardiovascular disease. As obesity is caused by adipocyte accumulation, therefore, investigation of adipocyte differentiation might reveal the underlying mechanism of these metabolic syndromes. Earlier studies have indicated adipocyte differentiation is mainly controlled by a transcriptional cascade involving PPARγ and members of the C/EBP family of transcription factors, which were also involved in insulin signaling pathway. Given that (i) Eps8 (EGFR pathway substrate number 8) is a common substrate of both receptor tyrosine kinase (EGFR) and non-receptor tyrosine kinase (Src); (ii) Eps8 overexpression activates Src kinase; and (iii) Src family kinase activity has been implicated in adipocyte differentiation, we wonder whether Eps8 also participates in the adipocyte formation. In this study, we found that Eps8 was elevated in the beginning and then faded off during the course of 3T3-L1 cells differentiated into adipocytes. In addition, attenuation of Eps8 decreased the accumulation of lipid droplet in these cells. Furthermore, insulin-induced PPAR and fatty acid synthase was abolished in Eps8-attenuated 3T3L1 cells. Consistently, Eps8 knockdown impaired insulin-activated ERK1/2 and STAT3. Taken together, our results suggested that Eps8 participated in insulin-induced PPAR and fatty acid synthase partly via ERK/STAT3-mediated pathways.

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