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  • 學位論文

巨噬細胞對於脂肪細胞中油滴形成與脂質代謝之影響

Effects of macrophage on lipid droplets formation and lipolysis of adipocytes

指導教授 : 楊舜鈞

摘要


肥胖屬低度慢性發炎反應,使浸潤於脂肪組織之巨噬細胞(adipose tissue macrophages)從抗發炎型(anti-inflammatory phenotype; M2)轉變為促發炎型(pro-inflammatory phenotype; M1),進而影響胰島素作用使脂肪細胞產生胰島素阻抗性(insulin resistance)。根據先前的研究結果,利用M2-conditioned medium培養脂肪前驅細胞後發現成熟脂肪細胞內的油滴減少,但其脂肪細胞分化過程中的標幟分子mRNA表現並未受到顯著影響。因此本實驗進一步推論M2-conditioned medium可能影響脂肪細胞的油滴形成、脂質代謝、脂肪細胞分化、脂質合成或油滴分解產物等。由實驗結果得知經M2-conditioned medium處理的組別與陽性對照組比較,參與油滴包袱蛋白(perilipin) 的mRNA和蛋白質表現量有明顯的降低,證明了M2-conditioned medium會影響油滴包袱以及油滴的成形,進而減少成熟脂肪細胞的產生。甘油是脂質分解路徑的終產物,在實驗結果中得知在M2-conditioned medium組別中比陽性對照組也有明顯的下降。最後利用共軛焦顯微鏡觀察細胞的形態,發現在M2-conditioned medium組別中其脂肪細胞的油滴體積較陽性對照組大,未來仍需做進一步地釐清相關機制。最後本實驗證明了M2-conditioned medium可能減少脂肪細胞內油滴的成形以及脂肪細胞的脂質代謝。

關鍵字

脂肪細胞 發炎 肥胖 油滴形成

並列摘要


Obesity is a chronic and low-grade inflammation, which can cause insulin resistance and affect the functions of adipocytes. Different types of macrophages (M1 or M2) may be involved in the metabolism of adipose tissue. In our previous studies, the conditioned medium from anti-inflammatory macrophages (M2) can affect the 3T3-L1 adipocytes differentiation and decrease the quantity of lipid droplets inside of adipocytes but the adipocyte differentiation marker (PPAR-γ, AP-2) had no significant change. Next, we focused on Fat-specific protein 27 (FSP27) and perilipin, both are lipid-droplet coating proteins and correlated with oil droplet formation and lipolysis. The results showed that the mRNA and protein level of perilipin are both decreased in the presence of M2-conditioned medium. It is proposed the M2-conditioned medium affects the expression of oil droplets coated protein or the process of droplet formation, leading to the reduction of mature adipose tissue. Our data also showed that, glycerol, the end product of lipolysis, were also decreased in the M2-conditioned medium group. However, the size of oil droplet seems to be larger in M2-conditioned medium group compared with positive group under microscopic observation. The detail molecular mechanism of this phenomenon is under further investigation. In summary, the M2-conditioned medium group are effectively reduced the droplet forming and lipid metabolism.

參考文獻


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