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研究方向:

 

肥胖已成為開發國家一個嚴重的健康問題。肥胖所引起的相關疾病,例如胰島素阻抗、糖尿病及心血管病變等,早已成為現代社會的醫療負擔。而談到肥胖,脂肪細胞扮演重要的角色,因為肥胖即是脂肪細胞堆積脂肪而增大的結果;而脂肪細胞的增大與其功能異常有莫大的關聯。脂肪細胞的功能受到荷爾蒙、神經系統及進食的調控,例如胰島素可促進脂肪細胞之脂肪合成、抑制脂肪分解、並促進血糖的吸收。在過去,脂肪細胞僅僅被認為只是儲存過多的能量之儲藏室。然而近年的研究結果發現,其實脂肪細胞分泌許多重要的物質,包括蛋白質與脂質因子,能夠主動調控身體其他組織或器官的生理功能。身體沒有脂肪細胞,過多的脂肪將被儲存在其他器官如肌肉與肝臟,造成這些器官的病變;同時缺乏脂肪細胞所分泌的重要物質,亦造成其他器官的功能異常。因此了解脂肪細胞的生理功能及其調控,將可幫助我們了解其與新陳代謝疾病的關係,並提供治療疾病之方法。

 

本實驗室將利用脂肪細胞株、初級細胞培養、及動物模式,探討下列幾個與脂肪細胞功能相關之重要問題:

 

  • 胰島素訊息傳遞之分子調控機制

  • 胰島素增敏藥物TZDs(糖尿病患用藥)之分子作用機制

  • 脂肪細胞分泌之分子機制與調控

  • 脂肪細胞與其他組織或器官之間的交互作用

 

   Obesity is a well-described epidemic in the westernized countries including Taiwan. It has been linked to a variety of adverse health issues such as cardiovascular diseases, insulin resistance, type 2 diabetes (T2DM), and certain cancer. Obesity is characterized as the increase of body adipose (fat tissue) mass, which can be due to the enlargement of adipocyte (fat cell), the primary cell type in the adipose tissue. The enlargement of adipocyte (hypertrophy) has been linked to its abnormal function. Under the normal condition, the biological function of adipocytes is under the regulation of hormones, neuronal stimuli, and the nutrients. Insulin, the hormone secreted from pancreas, regulates adipocyte function by promoting glucose uptake and lipogenesis, and suppressing lipolysis, therefore regulates lipid and glucose homeostasis. The adipocytes were once considered only the place to store excess fat. However the discovery of many important adipocyte-secreted factors that regulate the whole-body physiology makes the researchers reconsider the adipose tissue as an endocrine organ. Among the secreted factors are peptide hormones (named adipokines) and lipokines, which can regulate the physiology and function of other tissues. Without the adipose tissue, excess fat will be stored in other tissues such as muscle and liver, leading to malfunction of these tissues. Moreover, the lack of adipose tissue also results in the absence of adipokines normally secreted by adipocytes, leading to abnormal regulation of other tissues. Therefore, the understanding of the biological function and regulation of adipocytes will not only provide information on the mechanism by which the adipose tissue regulates body metabolism, but also the therapeutic methods in treating diseases.

 

We will use 3T3-L1 adipocytes, primary adipocyte culture, and the animal model to address the following questions:

  • Molecular mechanism of insulin signaling and insulin action in adipocytes

  • Molecular mechanism of the insulin-sensitizing drug thiazolidinediones (TZDs) in adipocytes

  • Molecular mechanism and regulation of adipokine secretion

  • The interaction of adipocytes and other tissues

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