血管附著蛋白-1與肥胖的關係

肥胖在台灣是一個盛行的疾病，導致罹患代謝症候群的比例以及死亡率的增加，但是肥胖的成因、或是肥胖如何導致代謝症候群的原因目前並不清楚。在利用3T3-L1 cell line與誘導後的脂肪細胞所做的differential display研究當中，我們發現了血管附著蛋白-1（vascular adhesion protein-1，簡稱VAP-1）在脂肪細胞分化後表現增加了好幾倍。此外，我們也利用semi-quantitative PCR證實了在肥胖小鼠的脂肪組織中，VAP-1的表現會增加。於是我們進一步探討VAP-1在人類肥胖所扮演的角色。首先，我們針對20位胖瘦不同的人，利用real-time reverse transcriptional PCR的方法，分析他們腹部脂肪組織VAP-1 mRNA的表現與臨床表徵的關係：發現無論是大網膜或是皮下的脂肪組織，VAP-1 mRNA的表現和身體質量指數（body mass index，BMI）、空腹血糖、空腹胰島素或是血脂肪都沒有顯著相關。此外，由於之前多位學者的研究報告指出，血中的VAP-1和代謝症候群有相關（雖然結論並不完全一致），所以我們進一步探討病態肥胖的病人在接受胃間隔手術後，血中VAP-1的改變與代謝症候群表徵的改變的關係。此研究共有20位病態肥胖的病人，平均BMI為38.84 kg/m2，我們紀錄下他們的開刀前後的臨床表徵以供分析，結果發現：開刀前，血清中VAP-1的值與空腹血糖成正相關（γ= 0.56，p =0.01），與空腹胰島素值成負相關（γ= -0.51，p = 0.021）。開刀後，血清中VAP-1的變化與腰圍（γ= -0.57，p = 0.011）、舒張壓（γ= -0.56，p = 0.015）及平均動脈壓（γ= -0.46，p = 0.055）的變化有顯著的負相關。在多元線性迴歸模式中，血清中VAP-1的變化在調整過年齡以及性別的影響後，仍可見到與腰圍（β= -2.36，p = 0.014）及舒張壓（β= -3.02，p = 0.017）的變化有顯著的負相關。同時，在調整過年齡以及性別的影響後，舒張壓的變化除了與HOMA-IR的變化有正相關外，也與VAP-1的變化有顯著的負相關。這結果意味著開刀後，血清中VAP-1的變化與腹部肥胖以及舒張壓的變化有關，值得進一步探討在腹部肥胖的病人當中，血清中的VAP-1是否可以調節血壓。

關鍵字

肥胖；血管附著蛋白-1 ；脂肪分佈；血壓

並列摘要

Objective: Circulating vascular adhesion protein-1 (VAP-1) has been shown, although inconsistently, to be associated with various phenotypes defined by metabolic syndrome. The current study explored whether the changes of serum VAP-1 level correlate with the changes in metabolic phenotypes following weight reduction surgery. Research Methods and Procedures: Clinical characteristics and serum VAP-1 levels in 20 morbidly obese subjects (mean BMI 38.84 kg/m2) were measured before and after gastric partition surgery. Results: Before surgery, serum VAP-1 levels correlated positively with fasting plasma glucose (γ= 0.56, p =0.01) and negatively with insulin levels (γ= -0.51, p = 0.021). Following surgery, the changes of serum VAP-1 level were negatively correlated with the changes of waist circumferences (γ= -0.57, p = 0.011), diastolic blood pressure (γ= -0.56, p = 0.015), and mean arterial pressure (γ= -0.46, p = 0.055). In multivariate regression, serum VAP-1 levels were negatively correlated with waist circumference (β= -2.36, p = 0.014) and diastolic blood pressure (β= -3.02, p = 0.017) after adjusting for age and gender. The change in diastolic blood pressure was correlated negatively with change of VAP-1 while positively with the change of HOMA-IR. Discussion: The results suggested that VAP-1 levels were correlated with fasting glucose and insulin levels in morbidly obese subjects. After gastric partition, the changes of VAP-1 level were associated with changes in visceral adiposity and diastolic blood pressure. Serum VAP-1 might modulate diastolic blood pressure independent on the changes of insulin resistance.

並列關鍵字

vascular adhesion protein-1 ； central obesity ； morbid obesity ； VAP-1 ； semicarbazide-sensitive amine oxidase ； blood pressure ； weight reduction

參考文獻

Abella, A., Marti, L., Camps, M., Claret, M., Fernandez-Alvarez, J., Gomis, R., Guma, A., Viguerie, N., Carpene, C., Palacin, M., Testar, X., and Zorzano, A. Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein-1 Activity Exerts an Antidiabetic Action in Goto-Kakizaki Rats. Diabetes 2003; 52(4):1004-1013.

Ahmad, F., Azevedo, J. L. J., Cortright, R., Dohm, G. L., and Goldstein, B. J. Alterations in skeletal muscle protein-tyrosine phosphatase activity and expression in insulin-resistant human obesity and diabetes. J Clin Invest 1997; 100:449-458.

Allison, D. B., Fontaine, K. R., Manson, J. E., Stevens, J., and VanItallie, T. B. Annual deaths attributable to obesity in the United States. JAMA 1999; 284:1530-1538.

Arvilommi, A. M., Salmi, M., and Jalkanen, S. Organ-selective regulation of vascular adhesion protein-1 expression in man. Eur.J Immunol. 1997; 27(7):1794-1800.

Bonithon-Kopp, C., Raison, J., Courbon, D., Bonhomme, G., Guy-Grand, B., and Ducimetiere, P. Relationships between 3-y longitudinal changes in body mass index, waist-to-hip ratio, and metabolic variables in an active French female population. Am J Clin Nutr 1992; 56(3):475-482.

國際替代計量

血管附著蛋白-1與肥胖的關係

全文下載

主題瀏覽