腹脂胖素對於脂質代謝相關基因之調控

Abstract

腹脂胖素（visfatin）是由脂肪細胞所分泌的激素之ㄧ，在腹脂中大量表現。 它能夠結合在胰島素受體上，但是與胰島素的鍵結位置不同，因此它具有類似胰島素的功能可降低血糖濃度，增加脂肪及肌肉細胞對葡萄糖攝入，減少肝臟細胞的葡萄糖釋出，並增加脂肪細胞中的三酸甘油酯產生，但卻不影響胰島素的作用。 為研究腹脂胖素對於豬隻脂質代謝相關基因的影響，本試驗建立了豬隻腹脂胖素重組蛋白表現系統，並成功獲得可溶性的重組蛋白。將重組蛋白處理分化的脂肪細胞24小時，可以增加細胞中介白素-6（IL-6）的mRNA表現（P<0.05），此結果與在免疫細胞的表現相似，證實此重組蛋白具有生理活性。利用重組蛋白所製造的豬腹脂胖素單株抗體，其對於抗原的敏感度可到達50 ng，抗體效價則可到達20000倍，並可測得豬血漿中特有的三種腹脂胖素。以腹脂胖素（100 ng/mL）及胰島素（100 ng/mL）處理脂肪前身細胞，發現腹脂胖素及胰島素都可提高脂肪前身細胞中的脂蛋白解脂酶（LPL）表現。胰島素亦會增加脂肪酸結合蛋白（aP2）表現，且細胞型態由前身細胞轉變為分化的脂肪細胞，但是腹脂胖素對aP2基因及脂肪細胞分化並無影響。而且在腹脂胖素及胰島素刺激的peroxisome proliferators activated receptorγ（PPARγ）mRNA的增加，其表現趨勢與LPL基因相似。已知PPARγ可增加LPL基因的表現，推測腹脂胖素在脂肪前身細胞，可能是經由PPARγ來調控LPL基因。而脂肪細胞處理腹脂胖素及胰島素（100 ng/mL）24小時後，可增加脂肪酸合成酶（FAS）的表現，但是sterol regulatory element binding proteins -1C（SREBP-1C）則不受影響（P<0.05）。腹脂胖素處理24小時也能增加脂肪細胞激素介白素-6（IL-6）的mRNA表現。 綜合上述，腹脂胖素在脂肪前身細胞可以增加LPL的表現，進而增加脂質攝入，而在脂肪細胞中腹脂胖素也能刺激FAS的表現而增加脂質生成，而且能藉由增進介白素-6表現。因此，推論腹脂胖素在豬脂肪細胞，具有類似胰島素功能可增加脂質生成，而腹脂胖素增加脂肪細胞的介白素-6表現。對於脂質代謝的影響，將是未來研究的方向。

Visfatin is a visceral fat-specific adipocytokine that function to mimic insulin actions, including regulation of plasma glucose and triacylglycerol concentrations and enhancement of glucose entry. To investigate the role of porcine visfatin in lipid metabolism, we first produce the adipose tissue recombinant porcine visfatin and used it as an immunogen for monoclonal antibody. In preadipocytes, the expression of lipoprotein lipase (LPL) and peroxisome proliferators activated receptor gamma (PPARγ) mRNA was increased by visfatin (100 ng/mL) or insulin (100 ng/mL) treatment for 8 days (p<0.05). Transcript to aP2 was promoted by 25-fold in the present of insulin treatment compared with control group (p<0.05), whereas visfatin treatment failed to increase an aP2 expression. Moreover, adipocyte differentiation was induced by insulin treatment after 8 days, whereas visfatin treatment exerted no such effect. In differentiated porcine adipocytes, treatment of insulin and visfatin for 24 hours increased FAS mRNA (p<0.05), but had no effect on sterol regulatory element binding proteins 1c (SREBP-1c) expression. Visfatin also upregulated interleukin-6（IL-6）expression in porcine adipocytes. In conclusion, results of study demonstrated that visfatin up-regulates LPL expression in preadipocytes and thereby may facilitate to lipid uptake. It also increases the expression of FAS in adipocytes, by which lipogenic activity may be enhanced. Interestingly, visfatin may also regulate IL-6 expression. Our data suggest that visfatin not only has similar lipogenic function as insulin, it also involved in regulating some cytokine in porcine adipocytes.