探討是否能利用提高棕色脂肪組織的活性藉此改善肥胖問題

Abstract

這些年，肥胖逐漸變成不可忽視的議題。肥胖的主要原因是能量的不平衡，當攝取的能量多於消耗的能量時，多於的能量將會形成脂肪堆積儲存在脂肪細胞內。人體內的脂肪組織主要分成三大類，白色脂肪組織、棕色脂肪組織、beige脂肪組織。白色脂肪組織主要功能為儲存能量，棕色脂肪組織則可以透過非顫抖性產熱non-shivering thermogenesis來消耗能量，beige脂肪組織在正常狀態下功能和白色組織相同，但受到特殊的刺激如低溫環境，將會棕化(browning)，其功能會類似於棕色組織。腎素-血管收縮素系統可以維持體液和血壓的平衡，若過度的活化將會導致肥胖，而第二型血管收縮素在腎素-血管收縮素系統扮演重要的角色，第二型血管收縮素可以透過血管收縮素第一型受體來調控血壓及大部分腎素-血管收縮素系統的反應，而血管收縮素第二型受體的功用目前還備受爭議，但多數認為其和第一型受體互相拮抗。甲狀腺素可以提高基礎代謝率，在人體內受到複雜的回饋機制來控制其表現量，不活化的左旋甲狀腺素鈉(T4)在脫碘酶作用下可以轉化為活化的三碘甲狀腺素(T3)進而影響身體的基礎代謝反應。在我的研究中，細胞實驗先使用第二型血管收縮素來影響棕色脂肪細胞內的產熱相關基因表現量，老鼠實驗則餵食高脂肪飼料使之肥胖，再加入三點甲狀腺素或是給予低溫環境，希望可以藉此提高棕色脂肪組織的活性或是增加beige脂肪組織的棕化率來改善肥胖問題。

Nowadays, obesity, resulting in lots of chronic diseases, has become an urgent issue. Imbalance between energy intake and expenditure causes obesity. When energy intake exceeds energy expenditure, extra exergy will be stored as fat in adipose tissue and leads to obesity. In human, adipose tissue can be divided into three classes: white adipose tissue storing energy, brown adipose tissue producing thermogenesis and beige adipocyte, which share same function with brown adipose tissue after specific stimulation like cold. Renin angiotensin system maintains the blood homeostasis and regulates blood pressure. Overactive renin angiotensin leads to obesity. Angiotensin II is the major regulator in renin angiotensin system, and it can regulate most action in renin angiotensin system through angiotensin type 1 receptor including blood pressure. The function of angiotensin type 2 receptor is still controversial while it is believe that the function is opposite of type 1 receptor. Thyroid hormones can increase basal metabolic rate and they are regulated by a complex feedback system. Inactive thyroxine can be converted into active triiodothyronine via deiodinases. My aim is against obesity via enhancing the thermogenesis in brown adipose tissue or promoting beige adipocyte undergo browning process. Therefore, I treated angiotensin II into cell or gave mice HFD to reach obesity. Next, I gave cells and mice stimulus including triiodothyronine or cold environment. In my research, I found that thermos-related genes decrease after treating the angiotensin II, while recover if I treated triiodothyronine or gave cold stimulation.